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Sample records for dose chemotherapy significantly

  1. The significance of relative dose intensity in adjuvant chemotherapy of pancreatic ductal adenocarcinoma-including the analysis of clinicopathological factors influencing relative dose intensity.

    PubMed

    Yabusaki, Norimitsu; Fujii, Tsutomu; Yamada, Suguru; Murotani, Kenta; Sugimoto, Hiroyuki; Kanda, Mitsuro; Nakayama, Goro; Koike, Masahiko; Fujiwara, Michitaka; Kodera, Yasuhiro

    2016-07-01

    Recently, it has been reported that the relative dose intensity (RDI) of adjuvant chemotherapy (AC) influences survival in various cancers, but there are very few reports about RDI in pancreatic ductal adenocarcinoma (PDAC). The optimal timing for initiation of AC for PDAC also remains unknown. The aim of this study was to identify the significance of RDI and the time interval between surgery and initiation of AC on survival of patients with PDAC. Clinicopathological factors that affect RDI were also investigated.A total of 311 consecutive PDAC patients who underwent curative resection between May 2005 and January 2015 were enrolled. Patients who underwent neoadjuvant chemoradiation, had UICC stage IV disease, or had early recurrences within 6 months were excluded, and the remaining 168 cases were analyzed.Patients with RDIs ≥80% (n = 79) showed significantly better overall survival (OS) compared to patients with RDIs <80% (n = 55) (median survival time (MST): 45.6 months, 26.0 months, P < 0.001). Patients with no AC (n = 34) showed the worst OS (MST: 20.8 months). Whether the AC was initiated earlier or later than 8 weeks after surgery did not influence survival, either in patients with RDIs ≥80% (P = 0.79) or in those with <80% (P = 0.73). Patients in the S-1 monotherapy group (n = 49) showed significantly better OS than patients in the gemcitabine monotherapy group (n = 51) (MST: 95.0 months, 26.0 months, respectively; P = 0.001). Univariate analysis conducted after adjusting for the chemotherapeutic drug used identified several prognostic factors; male gender (P = 0.01), intraoperative blood transfusion (P = 0.005), lymph node metastasis (P = 0.03), and postoperative WBC count (P = 0.03). Multivariate analysis identified intra-plus postoperative blood transfusion (P = 0.002) and high postoperative platelet-to-lymphocyte ratios (PLR) (P = 0.04) as independent predictors of poor RDI.Efforts to

  2. Stress Encountered by Significant Others of Cancer Patients Receiving Chemotherapy.

    ERIC Educational Resources Information Center

    Hart, Kay

    1987-01-01

    Attempts to identify and describe perceived stress and coping responses of family and nonfamily significant others of cancer patients receiving chemotherapy. Significant others were asked to identify stressful events related to treatment factors, relationship factors, and perception of the patient's condition. Coping responses were categorized in…

  3. High-dose chemotherapy in small-cell lung cancer.

    PubMed

    Pasini, F; Durante, E; De Manzoni, D; Rosti, G; Pelosi, G

    2002-01-01

    Small cell lung cancer (SCLC) is highly sensitive both to radiotherapy and chemotherapy. Given its high chemo sensitivity, even two decades ago, SCLC was one of the first malignancies deemed suitable for maximising the dose and dose intensity with the support of autologous bone marrow (ABMT). On the whole, results were disappointing and the procedure was practically abandoned. Nowadays some interest is again emerging due to improvements in supportive care, such as the availability of hematopoietic growth factors and the peripheral blood progenitor cells (PBPC). Data of 505 patients included in 26 studies were reviewed. About two thirds of these patients had LD (limited disease). Late intensification protocols were used in 311 patients who, however, represented only the 30% of the population initially given conventional chemotherapy. Of the patients not achieving complete remission (CR) after induction, high-dose induced a CR in 39% of the cases. The use of early intensification was reported in 8 studies including 194 patients. The CR rate was 51.5%. Overall, the probability of achieving the CR was 2-3 times higher in LD than in ED (extensive disease). Relapses occurred at the site of the primary in more than half of the cases, showing that the course of the disease was not modified by the use of high-dose chemotherapy. Toxic deaths occurred in 7% of the treated patients, without difference in the two treatment methods. Though the schedules were too variable to draw firm conclusions, the ICE (ifosfamide, carboplatin, etoposide) and the CBP (cyclophosphamide, cisplatin, carmustine) regimens apparently provided better results, with a 2-year survival rate of 30-50% in the LD subset. An european multicenter randomized trial is ongoing. At the present time high-dose chemotherapy is still to be considered experimental treatment, since major problems such as the selection of the patients, doses and timing of chemotherapy and radiotherapy remain unsolved. PMID:12552940

  4. Ocular toxicity following high dose chemotherapy and autologous transplant.

    PubMed

    Rubin, P; Hulette, C; Khawly, J A; Elkordy, M; Hussein, A; Vredenburgh, J J; Jaffe, G J; Peters, W P

    1996-07-01

    A 49-year-old woman received an autologous transplant for breast cancer. Six weeks later she noticed visual disturbance of the left eye which correlated with a visual field abnormality. There was a milder degree of visual disturbance in the right eye. Treatment with high-dose steroids partially stabilized the problem, which was felt to be an ischemic optic neuropathy. She ultimately died of respiratory failure. Pathology of the optic nerves revealed demyelination. Visual disturbances following high-dose chemotherapy are uncommon; the pathology to date has not been elucidated. Steroid therapy may be useful. PMID:8832031

  5. Optimal Treatment for Intracranial Germinoma: Can We Lower Radiation Dose Without Chemotherapy?

    SciTech Connect

    Yen, Sang-Hue; Chen, Yi-Wei; Huang, Pin-I

    2010-07-15

    Purpose: To review the effectiveness of reduced-dose and restricted-volume radiation-only therapy in the treatment of intracranial germinoma and to assess the feasibility of reducing or eliminating the use of chemotherapy. Methods and Materials: Between January 1996 and March 2007, a retrospective analysis was performed that included 38 patients who received either reduced radiation alone (30 Gy for 26 patients) or reduced radiation with chemotherapy (n = 12 patients). All 38 patients received extended focal (including whole-ventricle) irradiation and were followed up until February 2008. Overall survival (OS) and relapse-free survival (RFS) rates were calculated. Variables associated with survival were evaluated by univariate Cox proportional hazards regression. Results: Median follow-up was 62.4 months (range, 10.1-142.5 months). The total 5-year OS rate was 93.7%. The 5-year OS and RFS rates for patients receiving radiation only were 100% and 96.2%, respectively. The rates for those receiving radiation plus chemotherapy were 83.3 % and 91.7%, respectively (not statistically significant). No predictive factor was significantly associated with the OS or RFS rate. Chemotherapy had no significant effect on survival but was associated with a higher incidence of treatment-related toxicity. Conclusions: A further decrease in the radiation dose to 30 Gy with whole-ventricle irradiation is sufficient to treat selected patients with intracranial germinoma. Wide-field irradiation or chemotherapy should be avoided as these methods are unnecessary. Thus, reduction of the radiation dose to 30 Gy may be feasible, even without chemotherapy.

  6. Validity of reduced radiation dose for localized diffuse large B-cell lymphoma showing a good response to chemotherapy.

    PubMed

    Koiwai, Keiichiro; Sasaki, Shigeru; Yoshizawa, Eriko; Ina, Hironobu; Fukazawa, Ayumu; Sakai, Katsuya; Ozawa, Takesumi; Matsushita, Hirohide; Kadoya, Masumi

    2014-03-01

    To evaluate the validity of a decrease in the radiation dose for patients who were good responders to chemotherapy for localized diffuse large B-cell lymphoma (DLBCL), 91 patients with localized DLBCL who underwent radiotherapy after multi-agent chemotherapy from 1988-2008 were reviewed. Exclusion criteria were as follows: central nervous system or nasal cavity primary site, or Stage II with bulky tumor (≥10 cm). Of these patients, 62 were identified as good responders to chemotherapy. They were divided into two groups receiving either a higher or a lower radiation dose (32-50.4 Gy or 15-30.6 Gy, respectively). There were no statistically significant differences between the lower and higher dose groups in progression-free survival, locoregional progression-free survival or overall survival. Adaptation of decreased radiation dose may be valid for localized DLBCL patients who show a good response to chemotherapy. PMID:24187329

  7. High-dose Helical Tomotherapy With Concurrent Full-dose Chemotherapy for Locally Advanced Pancreatic Cancer

    SciTech Connect

    Chang, Jee Suk; Wang, Michael L.C.; Koom, Woong Sub; Yoon, Hong In; Chung, Yoonsun; Song, Si Young; Seong, Jinsil

    2012-08-01

    Purpose: To improve poor therapeutic outcome of current practice of chemoradiotherapy (CRT), high-dose helical tomotherapy (HT) with concurrent full-dose chemotherapy has been performed on patients with locally advanced pancreatic cancer (LAPC), and the results were analyzed. Methods and Materials: We retrospectively reviewed 39 patients with LAPC treated with radiotherapy using HT (median, 58.4 Gy; range, 50.8-59.9 Gy) and concomitant chemotherapy between 2006 and 2009. Radiotherapy was directed to the primary tumor with a 0.5-cm margin without prophylactic nodal coverage. Twenty-nine patients (79%) received full-dose (1000 mg/m{sup 2}) gemcitabine-based chemotherapy during HT. After completion of CRT, maintenance chemotherapy was administered to 37 patients (95%). Results: The median follow-up was 15.5 months (range, 3.4-43.9) for the entire cohort, and 22.5 months (range, 12.0-43.9) for the surviving patients. The 1- and 2-year local progression-free survival rates were 82.1% and 77.3%, respectively. Eight patients (21%) were converted to resectable status, including 1 with a pathological complete response. The median overall survival and progression-free survival were 21.2 and 14.0 months, respectively. Acute toxicities were acceptable with no gastrointestinal (GI) toxicity higher than Grade 3. Severe late GI toxicity ({>=}Grade 3) occurred in 10 patients (26%); 1 treatment-related death from GI bleeding was observed. Conclusion: High-dose helical tomotherapy with concurrent full-dose chemotherapy resulted in improved local control and long-term survival in patients with LAPC. Future studies are needed to widen the therapeutic window by minimizing late GI toxicity.

  8. Chemotherapy

    MedlinePlus

    ... saved articles window. My Saved Articles » My ACS » Chemotherapy Chemotherapy (chemo) usually refers to the use of ... better sense of control over your cancer treatment. Chemotherapy Basics How Is Chemotherapy Used to Treat Cancer? ...

  9. Combined chemoradiation for the management of nasal natural killer (NK)/T-cell lymphoma: elucidating the significance of systemic chemotherapy.

    PubMed

    Guo, Ye; Lu, Jiade J; Ma, Xuejun; Wang, Biyun; Hong, Xiaonan; Li, Xiaoqiu; Li, Jin

    2008-01-01

    The objective of this analysis was to evaluate the efficacy and treatment outcome of CHOP and CHOP combined with nitrosourea chemotherapy in natural killer (NK)/T-cell lymphoma of the nasal cavity. Sixty-three patients with NK/T-cell lymphoma of the nasal cavity were treated with CHOP or CHOP combined with oral nitrosourea chemotherapy between January 1997 and June 2005. By the Ann Arbor Lymphoma Staging Classification, 57 patients (90%) had Stage IE or IIE disease and six patients (10%) had Stage III or IV disease. All patients with Stage IE or IIE disease were intended to be treated curatively with combined chemoradiation; and patients who had Stage III or IV disease were treated with chemotherapy alone with curative intention. Chemotherapy consisted of: (1) up to six cycles of the standard CHOP based regimen, or (2) up to six cycles of the standard CHOP based regimen with oral Semustine dosed at 120 mg (or Lomustine dosed at 100mg) on day 1 of each chemotherapy cycle. External beam radiation therapy was delivered by daily conventional fractionation by Co-60 or 6MVx linear accelerator for patients with Stage IE or IIE disease. The radiation dose to the tumor bed was between 36 and 50 Gy with a median dose of 45 Gy. Fifty-three patients received chemotherapy prior to radiation, and four patients were treated with involved field radiation before chemotherapy. The median follow up for all 44 surviving patients was 31 months (range: 6-104 months). The 2-year progression-free survival (PFS) and overall survival (OS) rates were 60% and 70%, respectively. The PFS and OS of patients who were treated with or without oral nitrosourea in addition to CHOP were 73% vs. 44% (P=0.035) and 75% vs. 64% (P=0.276), respectively. Nine patients with Stage IE or IIE diseases developed disease progression during their planned treatment and died within 10 months after the initiation of treatment; Six patients who achieved complete response (CR) after planned chemoradiation developed

  10. A short course of induction chemotherapy followed by two cycles of high-dose chemotherapy with stem cell rescue for chemotherapy naive metastatic breast cancer.

    PubMed

    Elias, A D; Richardson, P; Avigan, D; Ibrahim, J; Joyce, R; Demetri, G; Levine, J; Warren, D; Arthur, T; Reich, E; Wheele, C; Frei, E; Ayash, L

    2001-02-01

    A single cycle of high-dose chemotherapy with stem cell support (HDC) in women with responsive metastatic breast cancer (BC) consistently achieves over 50% complete and near complete response (CR/nCR). This significant cytoreduction results in a median event-free survival (EFS) of 8 months, and approximately 20% 3-year and 16% 5-year EFS in selected patients. To improve long-term outcomes, new strategies to treat minimal residual tumor burden are needed. Increased total dose delivered can be achieved with two cycles of HDC. Critical design issues include shortening induction chemotherapy to avoid development of drug resistance and the use of different agents for each HDC cycle. We have determined the maximum tolerated dose (MTD) for paclitaxel combined with high-dose melphalan in the context of a double transplant and explored the impact of a short induction phase. Between June 1994 and August 1996, we enrolled 32 women with metastatic BC on to this phase I double transplant trial. Induction consisted of doxorubicin 30 mg/m2/day days 1-3 given for 2 cycles every 14 days with G-CSF 5 microg/kg s.c. days 4-12. Stem cell collection was performed by leukapheresis in each cycle when the WBC recovered to above 1000/microl. Patients with stable disease or better response to induction were eligible to proceed with HDC. HDC regimen I (TxM) included paclitaxel with dose escalation from 0 to 300 mg/m2 given on day 1 and melphalan 180 mg/m2 in two divided doses given on day 3. HDC regimen II was CTCb (cyclophosphamide 6 g/m2, thiotepa 500 mg/m2, and carboplatin 800 mg/m2 total doses) delivered by 96-h continuous infusion. At the first dose level of 150 mg/m2 paclitaxel by 3 h infusion, four of five patients developed dose-limiting toxicity consisting of diffuse skin erythema and capillary leak syndrome. Only two of these five completed the second transplant. Subsequently, paclitaxel was delivered by 24-h continuous infusion together with 96 h of dexamethasone and histamine

  11. [High-dose chemotherapy and residual tumor resection in male germ cell tumors].

    PubMed

    Lorch, A; Albers, P; Winter, C; Beyer, J

    2011-09-01

    As a consequence of the unsatisfactory results of conventional dose salvage regimens, in particular for patients with poor prognostic features at the time of relapse or in patients with refractory disease, high-dose chemotherapy (HDCT) was introduced into clinical practice in the late 1980s. The combination of carboplatin and etoposide (CE) still remains the backbone of most high-dose regimens. Multiple modifications with more dose escalations or addition of further drugs have been explored, most often with increased toxicity. With improved expertise in supportive care and the use of peripheral blood stem cells, hematopoetic recovery has been significantly shortened and the initial high treatment-related mortality reduced from more than 10% to about 3%. Since the incorporation of HDCT, even patients with unfavorable prognostic features or patients with second or subsequent relapses can achieve long-term remission. Following HDCT residual tumor resection plays a major role in achieving these long-term results. The proportion of vital residual tumor after HDCT is much higher than in patients after conventional chemotherapy. The role of HDCT remains controversial particularly as a first-line treatment and less so in the first salvage setting. As these patients are rare HDCT and residual tumor resection should only be be provided by high-volume centers with sufficient expertise in performing these complex procedures. PMID:21845425

  12. Clinically relevant doses of chemotherapy agents reversibly block formation of glioblastoma neurospheres

    PubMed Central

    Mihaliak, Alicia M.; Gilbert, Candace A.; Li, Li; Daou, Marie-Claire; Moser, Richard P.; Reeves, Andrew; Cochran, Brent H.; Ross, Alonzo H.

    2010-01-01

    Glioblastoma patients have a poor prognosis, even after surgery, radiotherapy, and chemotherapy with temozolomide or 1,3-bis(2-chloroethy)-1-nitrosourea. We developed an in vitro recovery model using neurosphere cultures to analyze the efficacy of chemotherapy treatments, and tested whether glioblastoma neurosphere initiating cells are resistant. Concentrations of chemotherapy drugs that inhibit neurosphere formation are similar to clinically relevant doses. Some lines underwent a transient cell cycle arrest and a robust recovery of neurosphere formation. These results indicate that glioblastoma neurospheres can regrow after treatment with chemotherapy drugs. This neurosphere recovery assay will facilitate studies of chemo-resistant subpopulations and methods to enhance glioblastoma therapy. PMID:20435409

  13. Low-dose docetaxel, estramustine and prednisolone combination chemotherapy for castration-resistant prostate cancer

    PubMed Central

    NAKANO, MAYURA; SHOJI, SUNAO; HIGURE, TARO; KAWAKAMI, MASAYOSHI; TOMONAGA, TETSURO; TERACHI, TOSHIRO; UCHIDA, TOYOAKI

    2016-01-01

    The objective of this study was to report our experience with weekly low-dose docetaxel (DOC) chemotherapy for patients with castration-resistant prostate cancer (CRPC). From 2007 to 2014, 39 consecutive patients received weekly low-dose DOC; the oncological effectiveness, side effects and tolerability were prospectively analyzed. The median patient age, serum prostate-specific antigen (PSA) level and Gleason score at diagnosis of prostate cancer were 71 years (range, 55–83 years), 187 ng/ml (range, 2.0–1711 ng/ml) and 8 (range, 5–10), respectively. The median number of cycles of DOC was 7 (range, 1–45 cycles). Of the 39 patients, the PSA level decreased by >50% in 13 (33%). In the multivariate analysis of prediction of patient overall survival, a decrease of the PSA level to <50% was a significant predictor (hazard ratio = 6.913; 95% confidence interval: 1.147–41.669; P=0.035). The median cancer-specific overall survival from the diagnosis of CRPC was 16.7 months (range, 2–54 months). Grade 3 toxicities were observed in 5 patients (13%); specifically, limb edema, nausea and hepatic disorders were detected in 2 (5%), 2 (5%) and 1 patient (3%), respectively. Treatment-related death (grade 5) occurred in 1 patient due to interstitial pneumonia after two courses of chemotherapy. The chemotherapy was completed in the majority of the patients (n=37, 94.8%) in the outpatient department, without interruption. These findings suggest that weekly low-dose DOC is feasible and safe for selected patients with CRPC, without treament with novel agents, such as abiraterone, enzalutamide and cabazitaxel. PMID:27284427

  14. Neutrophil dynamics during concurrent chemotherapy and G-CSF administration: Mathematical modelling guides dose optimisation to minimise neutropenia.

    PubMed

    Craig, Morgan; Humphries, Antony R; Nekka, Fahima; Bélair, Jacques; Li, Jun; Mackey, Michael C

    2015-11-21

    The choice of chemotherapy regimens is often constrained by the patient's tolerance to the side effects of chemotherapeutic agents. This dose-limiting issue is a major concern in dose regimen design, which is typically focused on maximising drug benefits. Chemotherapy-induced neutropenia is one of the most prevalent toxic effects patients experience and frequently threatens the efficient use of chemotherapy. In response, granulocyte colony-stimulating factor (G-CSF) is co-administered during chemotherapy to stimulate neutrophil production, increase neutrophil counts, and hopefully avoid neutropenia. Its clinical use is, however, largely dictated by trial and error processes. Based on up-to-date knowledge and rational considerations, we develop a physiologically realistic model to mathematically characterise the neutrophil production in the bone marrow which we then integrate with pharmacokinetic and pharmacodynamic (PKPD) models of a chemotherapeutic agent and an exogenous form of G-CSF (recombinant human G-CSF, or rhG-CSF). In this work, model parameters represent the average values for a general patient and are extracted from the literature or estimated from available data. The dose effect predicted by the model is confirmed through previously published data. Using our model, we were able to determine clinically relevant dosing regimens that advantageously reduce the number of rhG-CSF administrations compared to original studies while significantly improving the neutropenia status. More particularly, we determine that it could be beneficial to delay the first administration of rhG-CSF to day seven post-chemotherapy and reduce the number of administrations from ten to three or four for a patient undergoing 14-day periodic chemotherapy. PMID:26343861

  15. Brain Magnetic Resonance Imaging After High-Dose Chemotherapy and Radiotherapy for Childhood Brain Tumors

    SciTech Connect

    Spreafico, Filippo Gandola, Lorenza; Marchiano, Alfonso; Simonetti, Fabio; Poggi, Geraldina; Adduci, Anna; Clerici, Carlo Alfredo; Luksch, Roberto; Biassoni, Veronica; Meazza, Cristina; Catania, Serena; Terenziani, Monica; Musumeci, Renato; Fossati-Bellani, Franca; Massimino, Maura

    2008-03-15

    Purpose: Brain necrosis or other subacute iatrogenic reactions has been recognized as a potential complication of radiotherapy (RT), although the possible synergistic effects of high-dose chemotherapy and RT might have been underestimated. Methods and Materials: We reviewed the clinical and radiologic data of 49 consecutive children with malignant brain tumors treated with high-dose thiotepa and autologous hematopoietic stem cell rescue, preceded or followed by RT. The patients were assessed for neurocognitive tests to identify any correlation with magnetic resonance imaging (MRI) anomalies. Results: Of the 49 children, 18 (6 of 25 with high-grade gliomas and 12 of 24 with primitive neuroectodermal tumors) had abnormal brain MRI findings occurring a median of 8 months (range, 2-39 months) after RT and beginning to regress a median of 13 months (range, 2-26 months) after onset. The most common lesion pattern involved multiple pseudonodular, millimeter-size, T{sub 1}-weighted unevenly enhancing, and T{sub 2}-weighted hyperintense foci. Four patients with primitive neuroectodermal tumors also had subdural fluid leaks, with meningeal enhancement over the effusion. One-half of the patients had symptoms relating to the new radiographic findings. The MRI lesion-free survival rate was 74% {+-} 6% at 1 year and 57% {+-} 8% at 2 years. The number of marrow ablative courses correlated significantly to the incidence of radiographic anomalies. No significant difference was found in intelligent quotient scores between children with and without radiographic changes. Conclusion: Multiple enhancing cerebral lesions were frequently seen on MRI scans soon after high-dose chemotherapy and RT. Such findings pose a major diagnostic challenge in terms of their differential diagnosis vis-a-vis recurrent tumor. Their correlation with neurocognitive results deserves further investigation.

  16. A randomized, crossover comparison of standard-dose versus low-dose lenograstim in the prophylaxis of post-chemotherapy neutropenia.

    PubMed

    Juan, O; Campos, J M; Carañana, V; Sanchez, J J; Casañ, R; Alberola, V

    2001-06-01

    The aim of this trial was to compare the severity of neutropenia, the frequency of hospital admission for fever or infection, and the use of antibiotics among patients treated with a standard dose of lenograstim (263 microg/day of Euprotin) and others treated with half of this dose (131.5 microg/day) and the cost-effectiveness of each of the two doses. In this single-center study, 44 patients with solid tumors, who were all receiving standard-dose chemotherapy regimens following previous neutropenia or were at high risk of neutropenia, were randomized to receive lenograstim at a dose of 263 microg or 131.5 microg daily in the first cycle and then crossed over to the alternate dose for the following cycle. Crossover to the alternate dose was repeated for patients who received more than two cycles. Lenograstim was administered from day +5 to day +14. The absolute neutrophil count (ANC) was assessed on days +5, +8, +12 and +15 of each cycle. Statistical analysis was performed using a general lineal model for repeated samples. In all, 120 cycles were administered, with a median of 3 cycles (range 1-6). Only 4 patients received only 1 cycle. No statistically significant difference (P=0.324) in ANC was observed between standard-dose (mean 5.3, 10.7, 8.3, 11.4 x 10(9)/l) and low-dose (5.0, 8.6, 5.4, 7.5 x 10(9)/l) treatment at days +5, +8, +12 and + 15. Neutropenia grade III-IV was more common in patients receiving the low than in those receiving the standard dose of lenograstim (20% vs 12%, respectively), but the difference did not reach statistical significance (P=0.1). The incidence of fever and frequency of hospital admission were not affected by the dose of lenograstim: 3 patients presented with fever with the standard dose (all of those were admitted to hospital) and 2 patients with the low dose (1 was admitted). ANC in both groups (standard and low doses) was independent of chemotherapy line (first versus second or more). Lenograstim at a dose of 131.5 microg

  17. Pharmacokinetically guided algorithm of 5-fluorouracil dosing, a reliable strategy of precision chemotherapy for solid tumors: a meta-analysis

    PubMed Central

    Fang, Luo; Xin, Wenxiu; Ding, Haiying; Zhang, Yiwen; Zhong, Like; Luo, Hong; Li, Jingjing; Yang, Yunshan; Huang, Ping

    2016-01-01

    Precision medicine characterizes a new era of cancer care and provides each patient with the right drug at the right dose and time. However, the practice of precision dosing is hampered by a lack of smart dosing algorithms. A pharmacokinetically guided (PKG) dosing algorithm is considered to be the leading strategy for precision chemotherapy, although the effects of PKG dosing are not completely confirmed. Hence, we conducted a meta-analysis to evaluate the effects of the PKG algorithm of 5-fluorouracil (5-FU) dosing on patients with solid tumors. A comprehensive retrieval was performed to identify all of the prospective controlled studies that compared the body surface area (BSA)-based algorithm with the PKG algorithm of 5-FU in patients with solid tumors. Overall, four studies with 504 patients were included. The PKG algorithm significantly improved the objective response rate of 5-FU-based chemotherapy compared with the BSA-based algorithm. Furthermore, PKG dosing markedly decreased the risk of total grade 3/4 adverse drug reactions, especially those related to hematological toxicity. Overall, the PKG algorithm may serve as a reliable strategy for individualized dosing of 5-FU. PMID:27229175

  18. Pharmacokinetically guided algorithm of 5-fluorouracil dosing, a reliable strategy of precision chemotherapy for solid tumors: a meta-analysis.

    PubMed

    Fang, Luo; Xin, Wenxiu; Ding, Haiying; Zhang, Yiwen; Zhong, Like; Luo, Hong; Li, Jingjing; Yang, Yunshan; Huang, Ping

    2016-01-01

    Precision medicine characterizes a new era of cancer care and provides each patient with the right drug at the right dose and time. However, the practice of precision dosing is hampered by a lack of smart dosing algorithms. A pharmacokinetically guided (PKG) dosing algorithm is considered to be the leading strategy for precision chemotherapy, although the effects of PKG dosing are not completely confirmed. Hence, we conducted a meta-analysis to evaluate the effects of the PKG algorithm of 5-fluorouracil (5-FU) dosing on patients with solid tumors. A comprehensive retrieval was performed to identify all of the prospective controlled studies that compared the body surface area (BSA)-based algorithm with the PKG algorithm of 5-FU in patients with solid tumors. Overall, four studies with 504 patients were included. The PKG algorithm significantly improved the objective response rate of 5-FU-based chemotherapy compared with the BSA-based algorithm. Furthermore, PKG dosing markedly decreased the risk of total grade 3/4 adverse drug reactions, especially those related to hematological toxicity. Overall, the PKG algorithm may serve as a reliable strategy for individualized dosing of 5-FU. PMID:27229175

  19. Phase II dose-finding study of balugrastim in breast cancer patients receiving myelosuppressive chemotherapy.

    PubMed

    Gladkov, Oleg; Moiseyenko, Vladimir; Bondarenko, Igor N; Shparyk, Yaroslav; Barash, Steven; Adar, Liat; Bias, Peter; Avisar, Noa

    2015-06-01

    Balugrastim is a once-per-cycle, fixed-dose recombinant protein comprising human serum albumin and granulocyte colony-stimulating factor under development for prevention of severe neutropenia in cancer patients receiving myelosuppressive chemotherapy. This phase II, multicenter, active-controlled, dose-finding pilot study evaluated balugrastim safety and efficacy versus pegfilgrastim in breast cancer patients scheduled to receive myelosuppressive chemotherapy and investigated two doses with similar efficacy to pegfilgrastim for a subsequent phase III study. Patients received four cycles of doxorubicin/docetaxel chemotherapy and with each successive cycle were randomized sequentially to escalating doses of balugrastim [30 (n = 11), 40 (n = 21), or 50 mg (n = 20)] or a fixed dose of pegfilgrastim [6 mg (n = 26)] post-chemotherapy. Balugrastim doses were escalated as planned. The incidence of adverse events was similar among the balugrastim groups and between all balugrastim doses and pegfilgrastim. The most frequently reported adverse events were neutropenia, alopecia, and nausea. During cycle 1, severe neutropenia (absolute neutrophil count of <0.5 × 10(9)/L) occurred in 40, 67, and 50 % and febrile neutropenia occurred in 20.0, 9.5, and 10.0 % of patients receiving balugrastim 30, 40, and 50 mg, respectively; in patients receiving pegfilgrastim, 48 % experienced severe neutropenia and 8 % experienced febrile neutropenia. Duration of severe neutropenia (DSN) for each treatment group was 0.9, 1.6, 1.1, and 0.9 days, respectively. In the remaining three chemotherapy cycles, DSN was ≤1 day across all treatment groups. Balugrastim 50 mg was comparable to pegfilgrastim in terms of safety and overall efficacy in breast cancer patients receiving myelosuppressive chemotherapy. PMID:25966791

  20. [Orally administered polaprezinc significantly improves taste disorders in ovarian cancer patient undergoing chemotherapy].

    PubMed

    Nishijima, Shota; Yanase, Toru; Hata, Yuki; Tamura, Ryo; Tsuneki, Ikunosuke; Tamura, Masaki; Kurabayashi, Takumi

    2011-04-01

    The subject was a 75-year-old female who was receiving paclitaxel and carboplatin(TC)chemotherapy every other week after surgery for ovarian cancer. She greatly complained of taste disorders after four cycles(of every other week administration) of TC chemotherapy. To understand how the taste disorder was caused by chemotherapy objectively, taste examinations were conducted for the patient in our department. These examinations were conducted after receiving the informed consent from the patient. The authors conducted taste examinations for the patient using serum zinc measurement, tongue cell culture, electrogustometry, and filter paper disc tests(before and after starting chemotherapy), and found that her serum zinc level fell significantly after four cycles of chemotherapy. Orally disintegrating tablets of polaprezinc were then administered to the patient, after which the subjective symptom of taste disorder improved. Her serum zinc level increased, and the electrogustometric threshold rapidly fell(an improvement). The filter paper disc test showed some improvement, particularly in the glossopharyngeal nerve and the greater petrosal nerve field. PMID:21499007

  1. Hypofractionated Dose-Painting Intensity Modulated Radiation Therapy With Chemotherapy for Nasopharyngeal Carcinoma: A Prospective Trial

    SciTech Connect

    Bakst, Richard L.; Lee, Nancy; Pfister, David G.; Zelefsky, Michael J.; Hunt, Margie A.; Kraus, Dennis H.; Wolden, Suzanne L.

    2011-05-01

    Purpose: To evaluate the feasibility of dose-painting intensity-modulated radiation therapy (DP-IMRT) with a hypofractionated regimen to treat nasopharyngeal carcinoma (NPC) with concomitant toxicity reduction. Methods and Materials: From October 2002 through April 2007, 25 newly diagnosed NPC patients were enrolled in a prospective trial. DP-IMRT was prescribed to deliver 70.2 Gy using 2.34-Gy fractions to the gross tumor volume for the primary and nodal sites while simultaneously delivering 54 Gy in 1.8-Gy fractions to regions at risk of microscopic disease. Patients received concurrent and adjuvant platin-based chemotherapy similar to the Intergroup 0099 trial. Results: Patient and disease characteristics are as follows: median age, 46; 44% Asian; 68% male; 76% World Health Organization III; 20% T1, 52% T2, 16% T3, 12% T4; 20% N0, 36% N1, 36% N2, 8% N3. With median follow-up of 33 months, 3-year local control was 91%, regional control was 91%, freedom from distant metastases was 91%, and overall survival was 89%. The average mean dose to each cochlea was 43 Gy. With median audiogram follow-up of 14 months, only one patient had clinically significant (Grade 3) hearing loss. Twelve percent of patients developed temporal lobe necrosis; one patient required surgical resection. Conclusions: Preliminary findings using a hypofractionated DP-IMRT regimen demonstrated that local control, freedom from distant metastases, and overall survival compared favorably with other series of IMRT and chemotherapy. The highly conformal boost to the tumor bed resulted low rates of severe ototoxicity (Grade 3-4). However, the incidence of in-field brain radiation necrosis indicates that 2.34 Gy per fraction is not safe in this setting.

  2. Does High-Dose Antimicrobial Chemotherapy Prevent the Evolution of Resistance?

    PubMed Central

    Day, Troy; Read, Andrew F.

    2016-01-01

    High-dose chemotherapy has long been advocated as a means of controlling drug resistance in infectious diseases but recent empirical studies have begun to challenge this view. We develop a very general framework for modeling and understanding resistance emergence based on principles from evolutionary biology. We use this framework to show how high-dose chemotherapy engenders opposing evolutionary processes involving the mutational input of resistant strains and their release from ecological competition. Whether such therapy provides the best approach for controlling resistance therefore depends on the relative strengths of these processes. These opposing processes typically lead to a unimodal relationship between drug pressure and resistance emergence. As a result, the optimal drug dose lies at either end of the therapeutic window of clinically acceptable concentrations. We illustrate our findings with a simple model that shows how a seemingly minor change in parameter values can alter the outcome from one where high-dose chemotherapy is optimal to one where using the smallest clinically effective dose is best. A review of the available empirical evidence provides broad support for these general conclusions. Our analysis opens up treatment options not currently considered as resistance management strategies, and it also simplifies the experiments required to determine the drug doses which best retard resistance emergence in patients. PMID:26820986

  3. Low-dose Arsenic induces chemotherapy protection via p53/NF-κB-mediated metabolic regulation

    PubMed Central

    Ganapathy, Suthakar; Xiao, Shaowen; Seo, Seog-Jin; Lall, Rajuli; Yang, Mei; Xu, Teng; Su, Hang; Shadfan, Miriam; Ha, Chul S.; Yuan, Zhi-Min

    2015-01-01

    Most chemotherapeutical drugs kill cancer cells chiefly by inducing DNA damage, which unfortunately also causes undesirable injuries to normal tissues, mainly due to p53 activation. We report a novel strategy of normal tissue-protection that involves p53/NF-κB coordinated metabolic regulation. Pretreatment of untransformed cells with low doses of arsenic induced concerted p53 suppression and NF-κB activation, which elicited a marked induction of glycolysis. Significantly, this metabolic shift provided cells effective protection against cytotoxic chemotherapy, coupling the metabolic pathway to cellular resistance. Using both in vitro and in vivo models, we demonstrated an absolute requirement of functional p53 in arsenic-mediated protection. Consistently, a brief arsenic-pretreatment selectively protected only normal tissues but not tumors from toxicity of chemotherapy. An indispensable role of glycolysis in protecting normal tissues was demonstrated by using an inhibitor of glycolysis, 2-deoxyglucose, which almost totally abolished low-dose arsenic-mediated protection. Together, our work demonstrates that low-dose arsenic renders normal cells and tissues resistance to chemotherapy-induced toxicity by inducting glycolysis. PMID:23524579

  4. Renal function in high dose chemotherapy and autologous hematopoietic cell support treatment for breast cancer.

    PubMed

    Merouani, A; Shpall, E J; Jones, R B; Archer, P G; Schrier, R W

    1996-09-01

    Autologous and allogeneic bone marrow grafting both require cytoreductive therapy but only the allogeneic procedure requires immunosuppressive agents. Allogeneic bone marrow transplantation has been reported to be associated with a high incidence of both renal failure and veno-occlusive disease (VOD) of the liver, the combination of which is associated with a high morbidity and mortality. There is less known about the frequency and severity of these complications in patients undergoing autologous bone marrow transplantation. In the present study renal, hepatic and other complications were examined in 232 patients with Stages II/III and IV breast cancer who were treated with high-dose chemotherapy and autologous hematopoietic cell support with either marrow or peripheral blood progenitor cells. The post-treatment severity of the renal dysfunction was classified as follows: Grade 0, normal renal function [< 25% decrement in glomerular filtration rate (GFR)]; Grade 1. mild renal dysfunction (> 25% decrement in GFR but < a twofold increase in serum creatinine); Grade 2, > twofold rise in serum creatinine but no need for dialysis; Grade 3 > than twofold rise in serum creatinine and need for dialysis. There were 102 patients (44%) who were classified as Grade 0 and 81 patients (35%) who were classified as Grade 1 renal dysfunction. Severe renal dysfunction (Grades 2 and 3) was observed in 49 of the 232 patients (21%). This severe renal dysfunction of 21% compares with a previously reported 53% incidence of severe renal dysfunction for allogeneic bone marrow transplantation. Similarly, the frequency of hepatic VOD was less (4.7% or 11 of 232 patients) in this autologous bone marrow transplant study as compared to a reported incidence of hepatic VOD ranging from 22 to 53% in large series of allogeneic bone marrow transplant patients. The severe renal dysfunction (Grades 2 and 3) in the present autologous hematopoietic cell support study correlated most significantly with

  5. Roles of Radiation Dose and Chemotherapy in the Etiology of Stomach Cancer as a Second Malignancy

    SciTech Connect

    Belt-Dusebout, Alexandra W. van den; Aleman, Berthe M.P.; Besseling, Gijs; Bruin, Marie L. de; Hauptmann, Michael; Veer, Mars B. van't; Wit, Ronald de; Ribot, Jacques G.; Noordijk, Evert M.; Kerst, J. Martijn; Gietema, Jourik A.; Leeuwen, Flora E. van

    2009-12-01

    Purpose: To evaluate the roles of radiation dose, chemotherapy, and other factors in the etiology of stomach cancer in long-term survivors of testicular cancer or Hodgkin lymphoma. Methods and Materials: We conducted a cohort study in 5,142 survivors of testicular cancer or Hodgkin lymphoma treated in the Netherlands between 1965 and 1995. In a nested case-control study, detailed information on treatment, smoking, gastrointestinal diseases, and family history was collected for 42 patients with stomach cancer and 126 matched controls. For each subject, the mean radiation dose to the stomach was estimated. Relative risks (RRs) of stomach cancer and the radiation-related excess relative risk (ERR) per gray were calculated by conditional logistic regression analysis. Results: The risk of stomach cancer was 3.4-fold increased compared with the general population. The risk increased with increasing mean stomach dose (p for trend, <0.001), at an ERR of 0.84 per Gy (95% confidence interval [CI], 0.12-15.6). Mean stomach doses of more than 20 Gy were associated with a RR of 9.9 (95% CI, 3.2-31.2) compared with doses below 11 Gy. The risk was 1.8-fold (95% CI, 0.8-4.4) increased after chemotherapy and 5.4-fold (95% CI, 1.2-23.9) increased after high doses of procarbazine (>=13,000 mg) vs. <10,000 mg. The RR of smoking more than 10 cigarettes per day vs. no smoking was 1.6 (95% CI, 0.6-4.2). Conclusions: Stomach cancer risk is strongly radiation dose dependent. The role of chemotherapy, particularly of procarbazine and related agents, needs further study, because of the relatively small numbers of chemotherapy-treated subjects.

  6. A Randomized, Double-Blind Pilot Study of Dose Comparison of Ramosetron to Prevent Chemotherapy-Induced Nausea and Vomiting

    PubMed Central

    Kim, Ka-Rham; Kang, Gaeun; Ki, Myung-Seo; Shim, Hyun-Jeong; Hwang, Jun-Eul; Bae, Woo-Kyun; Chung, Ik-Joo; Kim, Jong-Keun; Jeong, Seongwook; Cho, Sang-Hee

    2015-01-01

    Purpose. This study was conducted to determine the optimal dose titration of ramosetron to prevent the Rhodes Index of Nausea, Vomiting, and Retching (RINVR). Methods. Patients treated with folic acid, 5-fluorouracil, and oxaliplatin were randomized into three groups (0.3 mg, 0.45 mg, and 0.6 mg ramosetron before chemotherapy). The pharmacokinetics and pharmacodynamics using RINVR were evaluated. Results. Seventeen, 15, and 18 patients received ramosetron at doses of 0.3 mg, 0.45 mg, and 0.6 mg, respectively. Tmax (h), Cmax (ng/mL), and AUClast (ng·h/mL) were associated with dose escalation significantly, showing a reverse correlation with the RINVR during chemotherapy. Acute CINV was observed in four patients (22.2%), two patients (14.3%), and one (5.6%) patient and a delayed CINV on day 7 was found in eight (47%), three (21.4%), and five (27.8%) patients in each group. The complete response rate was increased with dose escalation (35.3%, 50.0%, and 72.2% in each group) and also showed the tendency for decreasing moderate-to-severe CINV. Conclusions. This study shows a trend regarding the dose-response relationship for ramosetron to prevent CINV, including delayed emesis. It suggested that dose escalation should be considered in patients with CINV in a subsequent cycle of chemotherapy, and an individual approach using RINVR could be useful to monitor CINV. PMID:26421292

  7. High dose chemotherapy with stem cell support in the treatment of testicular cancer

    PubMed Central

    Popovic, Lazar; Matovina-Brko, Gorana; Popovic, Milica; Petrovic, Dragana; Cvetanovic, Ana; Vukojevic, Jelena; Jovanovic, Darjana

    2015-01-01

    Testicular germ cell cancer (TGCC) is rare form of malignant disease that occurs mostly in young man between age 15 and 40. The worldwide incidence of TGCC is 1.5 per 100000 man with the highest rates in North Europe. After discovery of cisplatin cure rates of TGCC are very favorable between 90%-95% and unlike most solid tumors, cure rate for metastatic TGCC is around 80%. Metastatic TGCC is usually treated with 3-4 cycles of bleomycin, etoposide, cisplatinum chemotherapy with or without retroperitoneal surgery and cure rates with this approach are between 41% in poor risk group and 92% in good risk group of patients. Cure rates are lower in relapsed and refractory patients and many of them will die from the disease if not cured with first line chemotherapy. High dose chemotherapy (HDCT) approach was used for the first time during the 1980s. Progress in hematology allowed the possibility to keep autologous haematopoietic stem cells alive ex-vivo at very low temperatures and use them to repopulate the bone marrow after sub-lethal dose of intesive myeloablative chemotherapy. Despite the fact that there is no positive randomized study to prove HDCT concept, cure rates in relapsed TGCC are higher after high dose therapy then in historical controls in studies with conventional treatment. Here we review clinical studies in HDCT for TGCC, possibilities of mobilising sufficient number of stem cells and future directions in the treatment of this disease. PMID:26730267

  8. High dose chemotherapy with stem cell support in the treatment of testicular cancer.

    PubMed

    Popovic, Lazar; Matovina-Brko, Gorana; Popovic, Milica; Petrovic, Dragana; Cvetanovic, Ana; Vukojevic, Jelena; Jovanovic, Darjana

    2015-12-26

    Testicular germ cell cancer (TGCC) is rare form of malignant disease that occurs mostly in young man between age 15 and 40. The worldwide incidence of TGCC is 1.5 per 100000 man with the highest rates in North Europe. After discovery of cisplatin cure rates of TGCC are very favorable between 90%-95% and unlike most solid tumors, cure rate for metastatic TGCC is around 80%. Metastatic TGCC is usually treated with 3-4 cycles of bleomycin, etoposide, cisplatinum chemotherapy with or without retroperitoneal surgery and cure rates with this approach are between 41% in poor risk group and 92% in good risk group of patients. Cure rates are lower in relapsed and refractory patients and many of them will die from the disease if not cured with first line chemotherapy. High dose chemotherapy (HDCT) approach was used for the first time during the 1980s. Progress in hematology allowed the possibility to keep autologous haematopoietic stem cells alive ex-vivo at very low temperatures and use them to repopulate the bone marrow after sub-lethal dose of intesive myeloablative chemotherapy. Despite the fact that there is no positive randomized study to prove HDCT concept, cure rates in relapsed TGCC are higher after high dose therapy then in historical controls in studies with conventional treatment. Here we review clinical studies in HDCT for TGCC, possibilities of mobilising sufficient number of stem cells and future directions in the treatment of this disease. PMID:26730267

  9. Neutron capture therapy: a comparison between dose enhancement of various agents, nanoparticles and chemotherapy drugs.

    PubMed

    Khosroabadi, Mohsen; Ghorbani, Mahdi; Rahmani, Faezeh; Knaup, Courtney

    2014-09-01

    The aim of this study is to compare dose enhancement of various agents, nanoparticles and chemotherapy drugs for neutron capture therapy. A (252)Cf source was simulated to obtain its dosimetric parameters, including air kerma strength, dose rate constant, radial dose function and total dose rates. These results were compared with previously published data. Using (252)Cf as a neutron source, the in-tumour dose enhancements in the presence of atomic (10)B, (157)Gd and (33)S agents; (10)B, (157)Gd, (33)S nanoparticles; and Bortezomib and Amifostine chemotherapy drugs were calculated and compared in neutron capture therapy. Monte Carlo code MCNPX was used for simulation of the (252)Cf source, a soft tissue phantom, and a tumour containing each capture agent. Dose enhancement for 100, 200 and 500 ppm of the mentioned media was calculated. Calculated dosimetric parameters of the (252)Cf source were in agreement with previously published values. In comparison to other agents, maximum dose enhancement factor was obtained for 500 ppm of atomic (10)B agent and (10)B nanoparticles, equal to 1.06 and 1.08, respectively. Additionally, Bortezomib showed a considerable dose enhancement level. From a dose enhancement point of view, media containing (10)B are the best agents in neutron capture therapy. Bortezomib is a chemotherapy drug containing boron and can be proposed as an agent in boron neutron capture therapy. However, it should be noted that other physical, chemical and medical criteria should be considered in comparing the mentioned agents before their clinical use in neutron capture therapy. PMID:24961208

  10. Low Dose Vaporized Cannabis Significantly Improves Neuropathic Pain

    PubMed Central

    Wilsey, Barth; Marcotte, Thomas D.; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

    2013-01-01

    We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling either medium dose (3.53%), low dose (1.29%), or placebo cannabis with the primary outcome being VAS pain intensity. Psychoactive side-effects, and neuropsychological performance were also evaluated. Mixed effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the two active dose groups’ results (p>0.7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo vs. low dose, 2.9 for placebo vs. medium dose, and 25 for medium vs. low dose. As these NNT are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being, for all intents and purposes, as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well-tolerated, and neuropsychological effects were of limited duration and readily reversible within 1–2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. PMID:23237736

  11. Significance of multidrug resistance gene-related proteins in the postoperative chemotherapy of gastric cancer

    PubMed Central

    Yu, Pengfei; Du, Yian; Yang, Litao; Fan, Sunfu; Wu, Jian; Zheng, Shusen

    2014-01-01

    Background: Multidrug resistance (MDR) is a serious problem in chemotherapy and is one of the main reasons for a poor outcome of gastric cancer. Study on the key proteins in multidrug resistance is necessary for the treatment of gastric cancer. Methods: The expression of ToPo II, MRP and GST-π in 119 gastric cancers was retrospectively examined, and the results were analyzed in correlation with clinicopathological data. ToPo II negative, MRP positive and GST-π positive were regarded as three risk factors which may be associated with chemotherapy resistance and poor prognosis. Patients were divided into two groups: high-risk group (≥2 risk factors) and the low-risk group (<2 risk factors), and the tumor recurrence and patients’ survival time of the two groups were also analyzed. Results: The positive rates of ToPo II, MRP and GST-π were 73.9%, 42.9% and 51.3%, respectively. The positively correlation between the expression of MRP and GST-π had been found. A significant correlation was shown between ToPo II expression and the level of differentiation. Significant differences with GST-π expression were also found in relation to the sex and differentiation. In the high-risk group, the 3-year survival rate of patients with/without chemotherapy were 62.1% and 52.0%, 5-year survival rates were 44.8% and 40.0%, but the difference was not statistically significant (P>0.05). In the low-risk group, the 3-year survival rate of patients with/without chemotherapy were 81.2% and 51.5%, 5-year survival rates were 71.9% and 45.5%, and the difference was statistically significant (P<0.05). Conclusions: Combined detection of MDR-related proteins ToPo II, MRP and GST-π may be prospectively valuable for postoperative individualized chemotherapy, and further predict the outcomes of gastric cancer patients. PMID:25550836

  12. No Salvage Using High-Dose Chemotherapy Plus/Minus Reirradiation for Relapsing Previously Irradiated Medulloblastoma

    SciTech Connect

    Massimino, Maura Gandola, Lorenza; Spreafico, Filippo; Biassoni, Veronica; Luksch, Roberto; Collini, Paola; Solero, Carlo N.; Simonetti, Fabio; Pignoli, Emanuele; Cefalo, Graziella; Poggi, Geraldina; Modena, Piergiorgio Ph.D.; Mariani, Luigi; Potepan, Paolo; Podda, Marta; Casanova, Michela; Pecori, Emilia; Acerno, Stefania; Ferrari, Andrea; Terenziani, Monica

    2009-04-01

    Purpose: Myeloablative regimens were frequently used for medulloblastoma relapsing after craniospinal irradiation (CSI): in 1997-2002, we used repeated surgery, standard-dose and myeloablative chemotherapy, and reirradiation. Methods and Materials: In 10 patients, reinduction included sequential high-dose etoposide, high-dose cyclophosphamide/vincristine, and high-dose carboplatin/vincristine, then two myeloablative courses with high-dose thiotepa ({+-} carboplatin); 6 other patients received two of four courses of cisplatin/etoposide. Hematopoietic precursor mobilization followed high-dose etoposide or high-dose cyclophosphamide or cisplatin/etoposide therapy. After the overall chemotherapy program, reirradiation was prescribed when possible. Results: Seventeen patients were treated: previous treatment included CSI of 19.5-36 Gy with posterior fossa/tumor boost and chemotherapy in 16 patients. Fifteen patients were in their first and 2 in their second and third relapses, respectively. First progression-free survival had lasted a median of 26 months. Relapse sites included leptomeninges in 9 patients, spine in 4 patients, posterior fossa in 3 patients, and brain in 1 patient. Three patients underwent complete resection of recurrence, and 10 underwent reirradiation. Twelve of 14 patients with assessable tumor had an objective response after reinduction; 2 experienced progression and were not given the myeloablative courses. Remission lasted a median of 16 months. Additional relapses appeared in 13 patients continuing the treatment. Fifteen patients died of progression and 1 died of pneumonia 13 months after relapse. The only survivor at 93 months had a single spinal metastasis that was excised and irradiated. Survival for the series as a whole was 11-93 months, with a median of 41 months. Conclusions: Despite responses being obtained and ample use of surgery and reirradiation, second-line therapy with myeloablative schedules was not curative, barring a few

  13. High-dose-rate vaginal brachytherapy with chemotherapy for surgically staged localized uterine serous carcinoma

    PubMed Central

    Higgins, Susan A.; Ratner, Elena; De Leon, Maria C.; Mani, Sheida; Silasi, Dan-Arin; Azodi, Masoud; Santin, Alessandro; Rutherford, Thomas; Schwartz, Peter E.

    2015-01-01

    Purpose To evaluate our institutional experience combining carboplatin-paclitaxel (C/T) chemotherapy with high-dose-rate (HDR) intra-vaginal brachytherapy (IVB) following comprehensive surgical staging in localized uterine serous carcinoma (USC). Material and methods Institutional chart review identified 56 patients with FIGO 2009 stage I-II USC treated between 2000-2010. Patients underwent total hysterectomy, bilateral salpingo-oopherectomy, and comprehensive surgical staging including pelvic and para-aortic lymph node dissection, omentectomy, and peritoneal cytology. Chemotherapy was 6 cycles of C/T, and the IVB dose was 14 Gy in 2 fractions, prescribed to 0.5 cm from the cylinder surface. Kaplan-Meier methods were used to estimate recurrence-free survival (RFS) and overall survival (OS). Results The median follow-up time was 49 months (range: 9-145). The 5-yr RFS and OS were 85% and 93%, respectively. In all cases of recurrence (n = 8), the first site of failure was extra-pelvic. There were no isolated vaginal recurrences, however, there was one vaginal apex recurrence recorded at 19 months in a patient with simultaneous lung metastases. Thus, the 2-year vaginal RFS was 98%. Conclusions Excellent vaginal/pelvic control rates were observed. Further study of HDR brachytherapy dose and fractionation in combination with chemotherapy is worthwhile. PMID:25829935

  14. Radiation dose escalation by simultaneous modulated accelerated radiotherapy combined with chemotherapy for esophageal cancer: a phase II study

    PubMed Central

    Zhai, Tiantian; Chang, Daniel; Chen, Zhijian; Huang, Ruihong; Zhang, Wuzhe; Lin, Kun; Guo, Longjia; Zhou, Mingzhen; Li, Dongsheng; Li, Derui; Chen, Chuangzhen

    2016-01-01

    The outcomes for patients with esophageal cancer (EC) underwent standard-dose radical radiotherapy were still disappointing. This phase II study investigated the feasibility, safety and efficacy of radiation dose escalation using simultaneous modulated accelerated radiotherapy (SMART) combined with chemotherapy in 60 EC patients. Radiotherapy consisted of 66Gy at 2.2 Gy/fraction to the gross tumor and 54Gy at 1.8 Gy/fraction to subclinical diseases simultaneously. Chemotherapy including cisplatin and 5fluorouracil were administered to all patients during and after radiotherapy. The data showed that the majority of patients (98.3%) completed the whole course of radiotherapy and concurrent chemotherapy. The most common ≥ grade 3 acute toxicities were neutropenia (16.7%), followed by esophagitis (6.7%) and thrombopenia (5.0%). With a median follow-up of 24 months (5-38) for all patients and 30 months (18-38) for those still alive, 11 patients (18.3%) developed ≥ Grade 3 late toxicities and 2 (3.3%) of them died subsequently due to esophageal hemorrhage. The 1- and 2-year local-regional control, distant metastasis-free survival, disease-free survival and overall survival rates were 87.6% and 78.6%, 86.0% and 80.5%, 75.6% and 64.4%, 86.7% and 72.7%, respectively. SMART combined with concurrent chemotherapy is feasible in EC patients with tolerable acute toxicities. They showed a trend of significant improvements in local-regional control and overall survival. Further follow-up is needed to evaluate the late toxicities. PMID:26992206

  15. Impressive Response to Dose-Dense Chemotherapy in a Patient with NUT Midline Carcinoma

    PubMed Central

    Maur, Michela; Toss, Angela; Dominici, Massimo; Frassoldati, Antonio; Corradini, Paolo; Maiorana, Antonio; Fontana, Annalisa; Conte, Pierfranco

    2015-01-01

    Patient: Male, 21 Final Diagnosis: NUT midline carcinoma Symptoms: Fatigue • fever • pain Medication: Romidepsin Clinical Procedure: Chemotherapy Specialty: Oncology Objective: Rare disease Background: NUT midline carcinoma (NMC) is a rare, highly lethal malignancy that results from a chromosome translocation and mostly arises in the midline organs. To date, no treatment has been established. Most patients receive combinations of chemotherapy regimens and radiation, and occasionally subsequent resection; nevertheless, patients have an average survival hardly exceeding 7 months. Case Report: A 21-year-old patient was admitted to our division with a large mediastinal mass with lung nodules, multiple vertebral metastases, and massive nodal involvement. In a few days, the patient developed a superior vena cava syndrome and an acute respiratory failure. Due to the rapid course of the disease, based on preliminary histology of poorly differentiated carcinoma, a dose-dense biweekly chemotherapy with paclitaxel, ifosfamide, and cisplatin was started. In the meantime, the diagnosis of NMC was confirmed. A surprising clinical benefit was obtained after the first cycle of chemotherapy, and after 6 cycles a PET-CT scan showed a very good response. At this point, radiotherapy was started but the disease progressed outside of the radiation field. The patient entered into a compassionate use protocol with Romidepsin, but a PET/CT scan after the first course showed disease progression with peritoneal and retroperitoneal carcinosis. A treatment with Pemetrexed was then started but the patient eventually died with rapid progressive disease. Conclusions: Our case history adds some interesting findings to available knowledge: NMC can be chemosensitive and radiosensitive. This opens the possibility to study more aggressive treatments, including high-dose consolidation chemotherapy and to evaluate the role of biological agents as maintenance treatments. PMID:26140332

  16. Combined therapy with thrombospondin-1 type I repeats (3TSR) and chemotherapy induces regression and significantly improves survival in a preclinical model of advanced stage epithelial ovarian cancer

    PubMed Central

    Russell, Samantha; Duquette, Mark; Liu, Joyce; Drapkin, Ronny; Lawler, Jack; Petrik, Jim

    2015-01-01

    Most women are diagnosed with epithelial ovarian cancer (EOC) at advanced stage, where therapies have limited effectiveness and the long-term survival rate is low. We evaluated the effects of combined antiangiogenic and chemotherapy treatments on advanced stage EOC. Treatment of EOC cells with a recombinant version of the thrombospondin-1 type I repeats (3TSR) induced more apoptotic cell death (36.5 ± 9.6%) in vitro compared to untreated controls (4.1 ± 1.4). In vivo, tumors were induced in an orthotopic, syngeneic mouse model of advanced stage EOC. Mice were treated with 3TSR (4 mg/kg per day) alone or in combination with chemotherapy drugs delivered with maximum tolerated dose or metronomic scheduling. Pretreatment with 3TSR induced tumor regression, normalized tumor vasculature, and improved uptake of chemotherapy drugs. Combination 3TSR and metronomic chemotherapy induced the greatest tumor regression (6.2-fold reduction in size compared to PBS-treated controls) and highest survival when treatment was initiated at advanced stage. 3TSR binding to its receptor, CD36 (cluster of differentiation 36), increased binding of CD36 and SHP-1, which significantly inhibited phosphorylation of the VEGF receptor. In this study, we describe a novel treatment approach and mechanism of action with 3TSR and chemotherapy that induces regression of advanced stage EOC and significantly improves survival.—Russell, S., Duquette, M., Liu, J., Drapkin, R., Lawler, J., Petrik, J. Combined therapy with thrombospondin-1 type I repeats (3TSR) and chemotherapy induces regression and significantly improves survival in a preclinical model of advanced stage epithelial ovarian cancer. PMID:25395453

  17. Primary central nervous system lymphoma: implication of high-dose chemotherapy followed by auto-SCT

    PubMed Central

    Reddy, N; Savani, BN

    2016-01-01

    Primary central nervous system lymphoma is a rare and distinct subtype of non-Hodgkin's lymphoma that is sensitive to radiation and chemotherapy. Decisions regarding the initial therapeutic approach are influenced by age and risk of therapy-related neurotoxicity. Despite several albeit small phase II studies, and the acknowledged need for larger prospective trials, there is supporting evidence to consider auto-SCT following induction chemotherapy in patients with good performance status. The international extranodal lymphoma study group is conducting a randomized phase II study comparing consolidative radiation therapy to high-dose therapy. Novel therapeutic options including early aggressive approach with upfront auto-SCT and strategies to prevent relapse following transplantation is an area of focus. PMID:22002486

  18. Transient hyperammonemia related to chemotherapy with continuous infusion of high-dose 5-fluorouracil.

    PubMed

    Liaw, C C; Liaw, S J; Wang, C H; Chiu, M C; Huang, J S

    1993-06-01

    Hyperammonemic encephalopathy has been reported in patients receiving chemotherapy (CT). It is characterized by abrupt alteration in mental status with markedly elevated plasma ammonium levels in the absence of obvious liver disease. This paper reports seven patients who developed transient hyperammonemia during chemotherapy. The regimens all included continuous infusion of high-dose 5-fluorouracil (5-FU). The onset of hyperammonemic encephalopathy was 1.5-4 days after the start of CT. Five cases had infection and six had prerenal azotemia at the time of hyperammonemia. After management, plasma ammonium levels all returned to the normal range within 2 days. Except for one persistent coma, status of consciousness cleared completely. The true mechanism of transient hyperammonemia is unclear. The excess production of ammonium due to metabolites of 5-FU added to precipitating factors such as infection, hypovolemia or constipation may be the explanation for transient hyperammonemia in our study. PMID:8358058

  19. Polaprezinc prevents oral mucositis in patients treated with high-dose chemotherapy followed by hematopoietic stem cell transplantation.

    PubMed

    Hayashi, Hiroko; Kobayashi, Ryo; Suzuki, Akio; Ishihara, Masashi; Nakamura, Nobuhiko; Kitagawa, Junichi; Kanemura, Nobuhiro; Kasahara, Senji; Kitaichi, Kiyoyuki; Hara, Takeshi; Tsurumi, Hisashi; Moriwaki, Hisataka; Itoh, Yoshinori

    2014-12-01

    We have previously reported that polaprezinc in sodium alginate suspension (P-AG) inhibited the incidence of oral mucositis induced by radiochemotherapy in patients with head and neck cancer. The present study was designed to investigate whether P-AG prevents oral mucositis in all patients (36 patients) with hematological malignancy receiving high-dose chemotherapy and radiotherapy followed by hematopoietic stem cell transplantation (HSCT). P-AG dramatically reduced the incidence of moderate-to-severe oral mucositis as compared to the control group treated with azulene gargle (20% versus 82% for grade ≥ 2, p<0.01; 0% versus 45% for grade ≥ 3, p<0.01). Pain associated with oral mucositis was also significantly (p=0.004) relieved by P-AG, resulting in a reduction in the use of analgesic agents (28% versus 73%, p=0.025). The incidence of xerostomia and taste disturbance tended to be lowered but not significantly by P-AG. On the other hand, P-AG had no influence on the incidence of other adverse events, tumor remission rate or the survival rate. Therefore, P-AG was found to be highly effective in preventing oral mucositis induced not only by radiochemotherapy for head and neck cancer but also by high-dose chemotherapy and radiotherapy followed by HSCT. PMID:25503160

  20. Neoadjuvant chemotherapy in breast cancer significantly reduces number of yielded lymph nodes by axillary dissection

    PubMed Central

    2014-01-01

    Background Neoadjuvant chemotherapy (NC) is an established therapy in breast cancer, able to downstage positive axillary lymph nodes, but might hamper their detectibility. Even if clinical observations suggest lower lymph node yield (LNY) after NC, data are inconclusive and it is unclear whether NC dependent parameters influence detection rates by axillary lymph node dissection (ALND). Methods We analyzed retrospectively the LNY in 182 patients with ALND after NC and 351 patients with primary ALND. Impact of surgery or pathological examination and specific histomorphological alterations were evaluated. Outcome analyses regarding recurrence rates, disease free (DFS) and overall survival (OS) were performed. Results Axillary LNY was significantly lower in the NC in comparison to the primary surgery group (median 13 vs. 16; p < 0.0001). The likelihood of incomplete axillary staging was four times higher in the NC group (14.8% vs. 3.4%, p < 0.0001). Multivariate analyses excluded any influence by surgeon or pathologist. However, the chemotherapy dependent histological feature lymphoid depletion was an independent predictive factor for a lower LNY. Outcome analyses revealed no significant impact of the LNY on local and regional recurrence rates as well as DFS and OS, respectively. Conclusion NC significantly reduces the LNY by ALND and has profound effects on the histomorphological appearance of lymph nodes. The current recommendations for a minimum removal of 10 lymph nodes by ALND are clearly compromised by the clinically already established concept of NC. The LNY of less than 10 by ALND after NC might not be indicative for an insufficient axillary staging. PMID:24386929

  1. Epoetin Theta with a New Dosing Schedule in Anaemic Cancer Patients Receiving Nonplatinum-Based Chemotherapy: A Randomised Controlled Trial

    PubMed Central

    Tjulandin, Sergei A; Bias, Peter; Elsässer, Reiner; Gertz, Beate; Kohler, Erich; Buchner, Anton

    2011-01-01

    Introduction Recombinant human erythropoietin (r-HuEPO) is used to treat symptomatic anaemia due to chemotherapy. A new r-HuEPO, Epoetin theta (Eporatio®), was investigated and compared to placebo in a randomised, double-blind clinical trial in adult cancer patients receiving nonplatinum-based chemotherapy. The primary efficacy endpoint was the responder rate (complete haemoglobin (Hb) response, i.e., Hb increase ≥2 g/dl) without the benefit of a transfusion within the previous 4 weeks. Research Design and Methods 186 patients were randomised to s.c. treatment for 12 weeks with either Epoetin theta (N = 95) or placebo (N = 91). The starting dose was 20,000 IU once weekly Epoetin theta or placebo. Results The incidence of complete Hb responders was significantly higher in the Epoetin theta group than in the placebo group (72.6 vs. 25.3%, P < 0.0001). More patients in the placebo group than in the Epoetin theta group received blood transfusions after randomisation (23 patients, 25.3% vs. 13 patients, 13.7%, P = 0.0277). The majority of patients with a complete Hb response had 20,000 IU/week as their maximum dose prior to response, indicating that a dose of 20,000 IU is an appropriate starting dose. The overall frequencies of adverse events (AEs) were similar in both treatment groups. Hypertension was the only AE that was more frequent in the Epoetin theta group compared to the placebo group (8.4 vs. 1.1%). Conclusions Epoetin theta showed a superior efficacy to placebo in terms of complete Hb response without blood transfusion within the previous 4 weeks. Treatment with Epoetin theta resulted in a statistically significant increase in mean haemoglobin levels compared to placebo. The overall frequencies of adverse events were similar in both treatment groups. PMID:22022341

  2. Hepatic intra-arterial chemotherapy (HIAC) of high dose mitomycin and epirubicin combined with caval chemofiltration versus prolonged low doses in liver metastases from colorectal cancer: a prospective randomized clinical study.

    PubMed

    Fiorentini, G; Poddie, D B; Cantore, M; Rossi, S; Tumolo, S; Dentico, P; Bernardeschi, P; Guadagni, S; Rossi, G; Valori, V M; De Simone, M

    2004-11-01

    A multicenter randomized study comparing high dose of mitomycin and epirubicin given as hepatic intra-arterial chemotherapy (HIAC) combined with caval chemofiltration (CF) versus low doses of the same drugs in unresectable liver metastases from colorectal cancer showed a significant improvement in the survival rate of the 20 patients treated with high dose compared to the 22 patients treated with low doses with a 1 year survival of 69% vs 39%. The median survival was 17 vs 11 months and the responses were 65% vs 33%. Toxicity was colangitis in 50% of patients considered. The extrahepatic progression was similar in the two groups (7/20 vs 8/22). PMID:15675479

  3. Evaluating the efficacies of Maximum Tolerated Dose and metronomic chemotherapies: A mathematical approach

    NASA Astrophysics Data System (ADS)

    Guiraldello, Rafael T.; Martins, Marcelo L.; Mancera, Paulo F. A.

    2016-08-01

    We present a mathematical model based on partial differential equations that is applied to understand tumor development and its response to chemotherapy. Our primary aim is to evaluate comparatively the efficacies of two chemotherapeutic protocols, Maximum Tolerated Dose (MTD) and metronomic, as well as two methods of drug delivery. Concerning therapeutic outcomes, the metronomic protocol proves more effective in prolonging the patient's life than MTD. Moreover, a uniform drug delivery method combined with the metronomic protocol is the most efficient strategy to reduce tumor density.

  4. Cardiac toxicity of trastuzumab in metastatic breast cancer patients previously treated with high-dose chemotherapy: a retrospective study

    PubMed Central

    Bengala, C; Zamagni, C; Pedrazzoli, P; Matteucci, P; Ballestrero, A; Da Prada, G; Martino, M; Rosti, G; Danova, M; Bregni, M; Jovic, G; Guarneri, V; Maur, M; Conte, P F

    2006-01-01

    HER-2 overexpression is associated to a poor prognosis in high-risk and metastatic breast cancer (MBC) patients treated with high-dose chemotherapy (HDC). HER-2 status is also a predictive factor and when trastuzumab is administered in combination with or sequentially to chemotherapy, a significant disease-free and/or overall survival improvement has been observed in HER-2+ early and MBC. Unfortunately, in both settings, trastuzumab is associated with an increased risk of cardiac dysfunction (CD). We have reviewed the clinical charts of HER-2-overexpressing MBC patients treated with trastuzumab after HDC. Age, baseline left ventricular ejection fraction (LVEF), radiation therapy on cardiac area, exposure to anthracycline, single or multiple transplant, high-dose agents, trastuzumab treatment duration were recorded as potential risk factors. In total, 53 patients have been included in the analysis. Median LVEF at baseline was 60.5%; at the end of trastuzumab (data available for 28 patients only), it was 55% (P=0.01). Five out of the 28 (17.9%) patients experienced CD. Two out of 53 (3.8%) patients developed a congestive heart failure. Age ⩾50 years and multiple transplant procedure were potential risk factors for CD. The overall incidence of CD observed in this population of HER-2+ MBC patients treated with trastuzumab after HDC is not superior to that reported with concomitant trastuzumab and anthracyclines. However, patients with age ⩾50 years or receiving multiple course of HDC should be considered at risk for CD. PMID:16570045

  5. Second Malignant Neoplasms in Survivors of Pediatric Hodgkin's Lymphoma Treated With Low-Dose Radiation and Chemotherapy

    PubMed Central

    O'Brien, Maureen M.; Donaldson, Sarah S.; Balise, Raymond R.; Whittemore, Alice S.; Link, Michael P.

    2010-01-01

    Purpose Survivors of childhood Hodgkin's lymphoma (HL) are at risk for second malignant neoplasms (SMNs). It is theorized that this risk may be attenuated in patients treated with lower doses of radiation. We report the first long-term outcomes of a cohort of pediatric survivors of HL treated with chemotherapy and low-dose radiation. Patients and Methods Pediatric patients with HL (n = 112) treated at Stanford from 1970 to 1990 on two combined modality treatment protocols were identified. Treatment included six cycles of chemotherapy with 15 to 25.5 Gy involved-field radiation with optional 10 Gy boosts to bulky sites. Follow-up through September 1, 2007, was obtained from retrospective chart review and patient questionnaires. Results One hundred ten children completed HL therapy; median follow-up was 20.6 years. Eighteen patients developed one or more SMNs, including four leukemias, five thyroid carcinomas, six breast carcinomas, and four sarcomas. Cumulative incidence of first SMN was 17% (95% CI, 10.5 to 26.7) at 20 years after HL diagnosis. The standard incidence ratio for any SMN was 22.9 (95% CI, 14.2 to 35) with an absolute excess risk of 93.7 cases per 10,000 person-years. All four secondary leukemias were fatal. For those with second solid tumors, the mean (± SE) 5-year disease-free and overall survival were 76% ± 12% and 85% ± 10% with median follow-up 5 years from SMN diagnosis. Conclusion Despite treatment with low-dose radiation, children treated for HL remain at significant risk for SMN. Sarcomas, breast and thyroid carcinomas occurred with similar frequency and latency as found in studies of children with HL who received high-dose radiation. PMID:20124178

  6. Capecitabine in patients with breast cancer relapsing after high-dose chemotherapy plus autologous peripheral stem cell transplantation--a phase II study.

    PubMed

    Jakob, A; Bokemeyer, C; Knop, S; Schupp, M; Mayer, F; Kanz, L

    2002-04-01

    Capecitabine, a tumor-selective, oral fluoropyrimidine, has demonstrated significant antitumor activity in patients with metastatic breast cancer. In this open-label monocenter phase II study the efficacy and safety of capecitabine in patients with metastatic breast cancer who relapsed after high-dose chemotherapy was examined. Female patients 18-65 years of age, with a histologically confirmed diagnosis of metastatic breast cancer, who relapsed after high-dose chemotherapy (adjuvant and/or metastatic) followed by autologous peripheral blood stem cell transplantation (PBSCT) and who had been treated in their course of the disease with an anthracycline and/or an anthracycline/taxane containing regimen were included into this clinical study. Capecitabine was applied as the first salvage chemotherapy at relapse after high-dose chemotherapy (1250 mg/m(2) b.i.d. p.o. for 14 days followed by 7 days rest period). Responding patients or those with stable disease after two treatment cycles were offered to continue treatment until tumor progression. Response rate, time to disease progression, survival, toxicity and quality of life were assessed. Fourteen patients between 35 and 60 years (median 45.5 years) entered this study and received a median number of 5 cycles (range 1-19) of capecitabine. All patients were evaluable for response. All patients had been pretreated with 1-2 cycles of high-dose chemotherapy plus PBSCT. Furthermore, 13 patients had additionally received local radiotherapy. On average, the patients showed metastatic disease in two organ sites (range 1-4 sites). One patient obtained a complete response and five patients a partial response, accounting for a response rate of 42.9% [95% confidence interval (17.7%; 71.1%)]. All responses were already achieved at the first observation time point 6 weeks after treatment initiation. Two further patients obtained stable disease for at least 12 weeks. At the time of final analysis all patients have progressed. Median

  7. Sustainable complete remission in recurrence yolk sac tumor patient treated with tandem high-dose chemotherapy and autologous stem cell.

    PubMed

    Abdullah, N A; Wang, P N; Huang, K G; Adlan, A S; Casanova, J

    2013-01-01

    A 21-year-old lady diagnosed with Stage 3 ovarian yolk sac tumor (YST) underwent primary cytoreductive fertility sparing surgery, followed by conventional courses of platinum-based chemotherapy and etoposide. Recurrence at cul-da-sac was noted after a short period of remission and secondary debulking performed followed by four cycles of conventional chemotherapy. The patient's disease progressed despite courses of treatments. A joint team management including a hematologist was commenced following the failure of conventional chemotherapies. Two cycles of high-dose chemotherapy (HDCT) with ifosfamide/cisplatin/etoposide (ICE) regimen, followed by autologous stem cell transplantation (ASCT) were given. With this salvage treatment, she remained in complete remission and disease-free for more than 30 months, while maintaining her reproductive function. These approaches appear to be effective as a salvage treatment in selected cases of patients with ovarian germ cell tumor, especially those who failed primary conventional chemotherapy. PMID:23781595

  8. Response of osteosarcoma to preoperative intravenous high-dose methotrexate chemotherapy: CT evaluation

    SciTech Connect

    Mail, J.T.; Cohen, M.D.; Mirkin, L.D.; Provisor, A.J.

    1985-01-01

    The histologic response of an osteosarcoma to preamputation high-dose methotrexate therapy can be used to determine the optimum maintenance chemotherapy regimen to be administered after amputation. This study evaluates computed tomography (CT) as a method of assessing the response of the tumor to the methotrexate therapy. Nine patients with nonmetastatic osteosarcoma of an extremity had a CT scan of the tumor at initial presentation. This was compared with a second CT scan after four courses of high-dose intravenous methotrexate. Each set of scans was evaluated for changes in bony destruction, soft-tissue mass, pattern of calcification, and extent of tumor involvement of the marrow cavity. These findings were correlated with the histologic response of the tumor as measured by the degree of tumor necrosis. The changes seen on CT correlated well with the degree of the histologic response in seven of the nine patients.

  9. Use of Concept of Chemotherapy-Equivalent Biologically Effective Dose to Provide Quantitative Evaluation of Contribution of Chemotherapy to Local Tumor Control in Chemoradiotherapy Cervical Cancer Trials

    SciTech Connect

    Plataniotis, George A. Dale, Roger G.

    2008-12-01

    Purpose: To express the magnitude of the contribution of chemotherapy to local tumor control in chemoradiotherapy cervical cancer trials in terms of the concept of the biologically effective dose. Methods and Materials: The local control rates of both arms of each study (radiotherapy vs. radiotherapy plus chemotherapy) reported from randomized controlled trials of concurrent chemoradiotherapy for cervical cancer were reviewed and expressed using the Poisson model for tumor control probability (TCP) as TCP = exp(-exp E), where E is the logarithm of cell kill. By combining the two TCP values from each study, we calculated the chemotherapy-related log cell kill as Ec = ln[(lnTCP{sub Radiotherapy})/(lnTCP{sub Chemoradiotherapy})]. Assuming a range of radiosensitivities ({alpha} = 0.1-0.5 Gy{sup -1}) and taking the calculated log cell kill, we calculated the chemotherapy-BED, and using the linear quadratic model, the number of 2-Gy fractions corresponding to each BED. The effect of a range of tumor volumes and radiosensitivities ({alpha} Gy{sup -1}) on the TCP was also explored. Results: The chemotherapy-equivalent number of 2-Gy fractions range was 0.2-4 and was greater in tumors with lower radiosensitivity. In those tumors with intermediate radiosensitivity ({alpha} = 0.3 Gy{sup -1}), the equivalent number of 2-Gy fractions was 0.6-1.3, corresponding to 120-260 cGy of extra dose. The opportunities for clinically detectable improvement are only available in tumors with intermediate radiosensitivity with {alpha} = 0.22-0.28 Gy{sup -1}. The dependence of TCP on the tumor volume decreases as the radiosensitivity increases. Conclusion: The results of our study have shown that the contribution of chemotherapy to the TCP in cervical cancer is expected to be clinically detectable in larger and less-radiosensitive tumors.

  10. Estimation of Radiobiologic Parameters and Equivalent Radiation Dose of Cytotoxic Chemotherapy in Malignant Glioma

    SciTech Connect

    Jones, Bleddyn . E-mail: b.jones.1@bham.ac.uk; Sanghera, Paul

    2007-06-01

    Purpose: To determine the radiobiologic parameters for high-grade gliomas. Methods and Materials: The biologic effective dose concept is used to estimate the {alpha}/{beta} ratio and K (dose equivalent for tumor repopulation/d) for high-grade glioma patients treated in a randomized fractionation trial. The equivalent radiation dose of temozolomide (Temodar) chemotherapy was estimated from another randomized study. The method assumes that the radiotherapy biologic effective dose is proportional to the adjusted radiotherapy survival duration of high-grade glioma patients. Results: The median tumor {alpha}/{beta} and K estimate is 9.32 Gy and 0.23 Gy/d, respectively. Using the published surviving fraction after 2-Gy exposure (SF{sub 2}) data, and the above {alpha}/{beta} ratio, the estimated median {alpha} value was 0.077 Gy{sup -1}, {beta} was 0.009 Gy{sup -2}, and the cellular doubling time was 39.5 days. The median equivalent biologic effective dose of temozolomide was 11.03 Gy{sub 9.3} (equivalent to a radiation dose of 9.1 Gy given in 2-Gy fractions). Random sampling trial simulations based on a cure threshold of 70 Gy in high-grade gliomas have shown the potential increase in tumor cure with dose escalation. Partial elimination of hypoxic cells (by chemical hypoxic cell sensitizers or carbon ion therapy) has suggested that considerable gains in tumor control, which are further supplemented by temozolomide, are achievable. Conclusion: The radiobiologic parameters for human high-grade gliomas can be estimated from clinical trials and could be used to inform future clinical trials, particularly combined modality treatments with newer forms of radiotherapy. Other incurable cancers should be studied using similar radiobiologic analysis.

  11. Consolidation Radiotherapy in Primary Central Nervous System Lymphomas: Impact on Outcome of Different Fields and Doses in Patients in Complete Remission After Upfront Chemotherapy

    SciTech Connect

    Ferreri, Andres Jose Maria; Verona, Chiara; Politi, Letterio Salvatore; Chiara, Anna; Perna, Lucia; Villa, Eugenio; Reni, Michele

    2011-05-01

    Purpose: Avoidance radiotherapy or reduction of irradiation doses in patients with primary central nervous system lymphoma (PCNSL) in complete remission (CR) after high-dose methotrexate (HD-MTX)-based chemotherapy has been proposed to minimize the neurotoxicity risk. Nevertheless, no study has focused on the survival impact of radiation parameters, as far as we know, and the optimal radiation schedule remains to be defined. Methods and Materials: The impact on outcome and neurologic performance of different radiation fields and doses was assessed in 33 patients with PCNSL who achieved CR after MTX-containing chemotherapy and were referred to consolidation whole-brain irradiation (WBRT). Patterns of relapse were analyzed on computed tomography-guided treatment planning, and neurologic impairment was assessed by the Mini Mental Status Examination. Results: At a median follow-up of 50 months, 21 patients are relapse-free (5-year failure-free survival [FFS], 51%). WBRT doses {>=}40 Gy were not associated with improved disease control in comparison with a WBRT dose of 30 to 36 Gy (relapse rate, 46% vs. 30%; 5-year FFS, 51% vs. 50%; p = 0.26). Disease control was not significantly different between patients irradiated to the tumor bed with 45 to 54 Gy or with 36 to 44 Gy, with a 5-year FFS of 35% and 44% (p = 0.43), respectively. Twenty patients are alive (5-year overall survival, 54%); WB and tumor bed doses did not have an impact on survival. Impairment as assessed by the Mini Mental Status Examination was significantly more common in patients treated with a WBRT dose {>=}40 Gy. Conclusion: Consolidation with WBRT 36 Gy is advisable in patients with PCNSL in CR after HD-MTX-based chemotherapy. Higher doses do not change the outcome and could increase the risk of neurotoxicity.

  12. Benefit from prolonged dose-intensive chemotherapy for infants with malignant brain tumors is restricted to patients with ependymoma: a report of the Pediatric Oncology Group randomized controlled trial 9233/34

    PubMed Central

    Strother, Douglas R.; Lafay-Cousin, Lucie; Boyett, James M.; Burger, Peter; Aronin, Patricia; Constine, Louis; Duffner, Patricia; Kocak, Mehmet; Kun, Larry E.; Horowitz, Marc E.; Gajjar, Amar

    2014-01-01

    Background The randomized controlled Pediatric Oncology Group study 9233 tested the hypothesis that dose-intensive (DI) chemotherapy would improve event-free survival (EFS) for children <3 years of age with newly diagnosed malignant brain tumors. Methods Of 328 enrolled eligible patients, diagnoses were medulloblastoma (n = 112), ependymoma (n = 82), supratentorial primitive neuroectodermal tumor (sPNET, n = 38) and other malignant brain tumors (n = 96), and were randomized to 72 weeks of standard dose chemotherapy (Regimen A, n = 162) or DI chemotherapy (Regimen B, n = 166). Radiation therapy (RT) was recommended for patients with evidence of disease at completion of chemotherapy or who relapsed within 6 months of chemotherapy completion. Results Distributions of EFS for Regimens A and B were not significantly different (P = 0.32) with 2- and 10-year rates of 22.8% ± 3.3% and 15.4% ± 3.7%, and 27.1% ± 3.4% and 20.8% ± 3.8%, respectively. Thus, the study hypothesis was rejected. While distributions of EFS and OS were not significantly different between Regimens A and B for patients with medulloblastoma and sPNET, DI chemotherapy resulted in significantly improved EFS distribution (P = .0011) (2-year EFS rates of 42.1% vs. 19.6% with SD chemotherapy), but not OS distribution, for patients with centrally confirmed ependymoma. The degree of surgical resection affected EFS, OS or both for most tumor groups. Approximately 20%, 40% and 20% of patients with medulloblastoma, ependymoma treated with DI chemotherapy, and sPNET, respectively appear to have been cured without RT. Of 11 toxic deaths on study, 10 occurred on the DI chemotherapy arm. Conclusions Prolonged dose-intensive chemotherapy given to infants with malignant brain tumors resulted in increased EFS only for patients with ependymoma. PMID:24335695

  13. High-dose chemotherapy in relapsed or refractory Hodgkin lymphoma patients: a reappraisal of prognostic factors.

    PubMed

    Cocorocchio, E; Peccatori, F; Vanazzi, A; Piperno, G; Calabrese, L; Botteri, E; Travaini, L; Preda, L; Martinelli, G

    2013-03-01

    High-dose chemotherapy (HDCT) has a consolidated role in the treatment of patients with refractory or relapsed Hodgkin lymphoma (HL). We report clinical results of 97 HL patients who underwent HDCT for refractory (62 patients) or relapsed (35 patients) diseases in Istituto Europeo di Oncologia, from 1995 to 2009. Treatment included high-dose carmustine, etoposide, cytarabine and melphalan in 84 patients and high-dose idarubicin and melphalan in 13 patients with subsequent peripheral hemopoietic stem cells transplant. Outcomes were evaluated in terms of progression-free survival (PFS) and overall survival (OS). In order to identify prognostic factors for outcome, a multivariate analysis for age, sex, disease status (refractory/relapsed), disease stage, B symptoms, presence of extranodal involvement, bulky disease, elevated lactate dehydrogenase, number of previous chemotherapy lines, remission status before transplant, 18F-fluoro-deoxy-d-glucose positron emission tomography ((18) FDG-PET) status before and after transplant was done. A clinical response was achieved in 91% of patients, with complete remissions in 76/97 patients. With a median follow-up of 45 months (range 1-164 months), 5-year PFS and OS were 64% and 71%, respectively. Remission status after induction therapy, 18F-fluoro-deoxy-d-glucose positron emission tomography status before and after transplant were the most important prognostic factors for PFS and OS in univariate or multivariate analyses. HDCT is able to induce a high remission rate and a prolonged PFS in more than 50% of the patients with refractory and relapsed HL. PMID:22473680

  14. Dose-Dense Chemotherapy in Metastatic Breast Cancer: Shortening the Time Interval for a Better Therapeutic Index.

    PubMed

    Schmidt, Marcus

    2016-02-01

    Despite the advancement of targeted therapies in metastatic breast cancer, chemotherapy is still of pivotal importance. The concept of dose density is known to increase the efficacy of chemotherapy. In metastatic disease, preservation of the quality of life is equally important. Because of this, weekly regimens are a cornerstone in metastatic disease. Taxanes like paclitaxel or nab-paclitaxel as well as antracyclines are often used in palliative treatment. Further advances to increase dose density have led to the concept of daily metronomic schedules with oral chemotherapeutic drugs like cyclophosphamide, capecitabine, or vinorelbine. Metronomic chemotherapy affects tumor angiogenesis and also weakens immunosuppressive regulatory T cells, promoting better control of tumor progression. Weekly or daily dose-dense regimens are a reasonable compromise between efficacy and toxicity to improve the therapeutic index. This is most important for the treatment of chronic disease where palliation and preservation of quality of life are vital. PMID:27051392

  15. High dose chemotherapy with peripheral blood stem cells transplantation in patients with relapsed or refractory lymphomas preliminary reports.

    PubMed

    Chang, C S; Lin, S F; Huang, S M; Liu, T C; Chen, T P; Yeh, C J

    1997-03-01

    High dose chemotherapy with peripheral blood stem cells transplantation (PBSCT) has been used worldwide in the treatment of patients with various hematological malignancies and other solid tumors. It has just come into use as a salvage therapy in various malignancies in Taiwan in recent years. We report eight cases with relapsed or refractory lymphoma treated with high dose chemotherapy and PBSCT. Our results showed all cases but one achieved complete remission. The mean days of white cell recovery were 10 days to > 500/microliter (ranges, 8-16 days) and 12 days to > 1,000/microliter (ranges, 9-19 days). The mean days to platelet transfusion independent, i.e. platelet > 20,000/microliters, was 14 days. No specific side effect was noted except death in one case on D+9 during cytopenia state. Four patients relapsed and died during the follow-up after PBSCT. From our preliminary results we suggest that high dose chemotherapy with PBSCT could be used as a salvage therapy in patients with relapsed or refractory lymphomas with favorable and sustained hematological recovery. Most cases were tolerable with myeloablative chemotherapy and re-achieved remission, however, remission duration was still short and relapse remained the main problem to be overcome. The long term effects of high dose chemotherapy with PBSCT still need further study. PMID:9109301

  16. Tumor angiogenesis as prognostic and predictive marker for chemotherapy dose-intensification efficacy in high-risk breast cancer patients within the WSG AM-01 trial.

    PubMed

    Gluz, Oleg; Wild, Peter; Liedtke, Cornelia; Kates, Ronald; Mendrik, Heiko; Ehm, Elisabeth; Artinger, Verena; Diallo-Danebrock, Raihanatou; Ting, Evelyn; Mohrmann, Svjetlana; Poremba, Christopher; Harbeck, Nadia; Nitz, Ulrike; Hartmann, Arndt; Gaumann, Andreas

    2011-04-01

    The goal of this analysis was to characterize the survival impact of angiogenesis in the patients with high-risk breast cancer, particularly the predictive impact on benefit from dose intensification of adjuvant chemotherapy. Formalin-fixed tissue sample of 152 patients treated as part of the WSG AM-01 trial by either high-dose or conventional dose-dense chemotherapy were analyzed. Angiogenic activity was measured using microvessel count and vascular surface area (VSA) determined by the expression of vascular markers CD31 (n = 128) and CD105/endoglin (n = 130). Protein molecular breast cancer subclasses were analyzed by k-means clustering (k = 5). The univariate impact of factors on event-free (EFS) and overall survival (OS) was tested by log-rank statistics and quantified by univariate Cox analysis. Multivariate survival analysis included factors significant in univariate analysis, as well as interactions was performed for EFS. Both VSA/CD31 (P = 0.004) and VSA/CD105 (P = 0.003) were significantly higher among cases with increased Ki-67. A significant association with molecular subtypes was also found for VSA/CD105: in patients with basal-like/Her-2 subtypes, mean was 1.72 versus 1.24 in patients with other subtypes (P < 0.001). Elevated VSA/CD105 was associated with both significantly decreased EFS (P = 0.01) and OS (P = 0.02). Increased tumor size and positive Her-2 status were also prognostic for poorer EFS. The benefit of dose intensification for EFS was seen in those low-VSA/CD105 patients. The result was evident both in univariate and in multivariate survival analysis including all factors that were significant at the univariate level. Expression of angiogenesis markers may mirror or confer resistance to chemotherapy in the patients with breast cancer, particularly within the context of dose intensified chemotherapy. Highly angiogenic tumors may not derive sufficient benefit from dose intensification of chemotherapy alone. Our findings may serve as a

  17. Salvage high-dose chemotherapy for children with extragonadal germ-cell tumours

    PubMed Central

    De Giorgi, U; Rosti, G; Slavin, S; Yaniv, I; Harousseau, J L; Ladenstein, R; Demirer, T; Dini, G

    2005-01-01

    We reviewed the European Group for Blood and Marrow Transplantation (EBMT) experience with salvage high-dose chemotherapy (HDC) in paediatric patients with extragonadal germ-cell tumour (GCT). A total of 23 children with extragonadal GCT, median age 12 years (range 1–20), were treated with salvage HDC with haematopoietic progenitor cell support. The GCT primary location was intracranial site in nine cases, sacrococcyx in eight, retroperitoneum in four, and mediastinum in two. In all, 22 patients had a nongerminomatous GCT and one germinoma. Nine patients received HDC in first- and 14 in second- or third-relapse situation. No toxic deaths occurred. Overall, 16 of 23 patients (70%) achieved a complete remission. With a median follow-up of 66 months (range 31–173 months), 10 (43%) are continuously disease-free. Of six patients who had a disease recurrence after HDC, one achieved a disease-free status with surgical resection followed by chemotherapy and radiotherapy. In total, 11 patients (48%) are currently disease-free. Eight of 14 patients (57%) with extracranial primary and three of nine patients (33%) with intracranial primary GCT are currently disease-free. HDC induced impressive long-term remissions as salvage treatment in children with extragonadal extracranial GCTs. Salvage HDC should be investigated in prospective trials in these patients. PMID:16106248

  18. Profile of netupitant/palonosetron (NEPA) fixed dose combination and its potential in the treatment of chemotherapy-induced nausea and vomiting (CINV).

    PubMed

    Navari, Rudolph M

    2015-01-01

    Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient risk factors significantly influence CINV. The use of a combination of a 5-hydroxytryptamine-3 (5-HT3) receptor antagonists, dexamethasone, and a neurokinin-1 (NK-1) receptor antagonist has significantly improved the control of acute and delayed emesis in single-day chemotherapy. Palonosetron, a second generation 5-HT3 receptor antagonist with a different half-life, different binding capacity, and a different mechanism of action than the first generation 5-HT3 receptor antagonists, appears to be the most effective agent in its class. Netupitant, is a new NK-1 receptor antagonist with a high binding affinity, a long half-life of 90 hours, is metabolized by CYP3A4, and is an inhibitor of CYP3A4. NEPA is an oral fixed-dose combination of netupitant and palonosetron which has recently been employed in Phase II and Phase III clinical trials for the prevention of CINV in patients receiving moderately and highly emetogenic chemotherapy (MEC and HEC). The clinical trials demonstrated that NEPA (300 mg of netupitant plus 0.50 mg of palonosetron) significantly improved the prevention of CINV compared to the use of palonosetron alone in patients receiving either HEC or MEC. The clinical efficacy was maintained over multiple cycles of chemotherapy. NEPA (Akynzeo(®)) has recently been approved by the Food and Drug Administration (FDA) to treat nausea and vomiting in patients undergoing cancer chemotherapy. PMID:25552904

  19. A non-comparative phase II study of dose intensive chemotherapy with doxorubicin and ifosfamide followed by high dose ICE consolidation with PBSCT in non-resectable, high grade, adult type soft tissue sarcomas.

    PubMed

    Hartmann, Jörg Thomas; Horger, M; Kluba, T; Königsrainer, A; de Zwart, P; von Weyhern, C Hann; Eckert, F; Budach, W; Bokemeyer, C

    2013-12-01

    The objective was to determine the role of dose intensive induction chemotherapy in patients with soft tissue sarcomas (STS) that were considered unresectable. Treatment consisted of 2-3 cycles of doxorubicin (Dox) and ifosfamide (Ifo) followed by high dose chemotherapy with ifosfamide, carboplatin, etoposide (HD-ICE) plus peripheral blood stem cell transplantation (PBSCT). 30 out of 631 consecutive patients, median age 46 years (21-62), with high grade STS were included. 29 patients completed at least 2 cycles of Dox/Ifo. HD-ICE was withheld because of progressive disease (PD) in 5 patients, neurotoxicity in 6 cases, insufficient peripheral blood stem cell (PBSC) mobilization, complete remission (CR) and refusal in 1 patient each. HD-ICE was associated with non-haematological grade III toxicity including emesis, mucositis, fever, neurotoxicity, and transaminase level elevation. Two additional patients attained a partial response after HD-ICE. Overall, 24 of 30 (80%) patients underwent surgery, with complete tumor resections in 19 patients (63% of all patients, 79% of the operated subgroup); however, 2 of these required amputation. After a median follow up period of 50 months in surviving patients (range, 26-120), 5-year PFS and OS rates were 39% and 48%, respectively. Induction chemotherapy plus consolidation HD-ICE is generally feasible, but is associated with significant neurotoxicity. The advantage of HD-ICE over conventional dose chemotherapy plus external beam radiation therapy (EBRT) in non-resectable disease remains unproven. PMID:24091981

  20. Clinical Significance of CA125 Level after the First Cycle of Chemotherapy on Survival of Patients with Advanced Ovarian Cancer

    PubMed Central

    Lee, Maria; Chang, Min Young; Yoo, Hanna; Lee, Kyung Eun; Chay, Doo Byung; Cho, Hanbyoul; Kim, Young Tae

    2016-01-01

    Purpose To determine the most powerful cancer antigen 125 (CA125)-related prognostic factor for advanced epithelial ovarian cancer (EOC) and to identify cut-off values that distinguish patients with a poor prognosis from those with a good prognosis. Materials and Methods We included 223 patients who received staging laparotomy and were diagnosed with stage IIC–IV serous EOC. Cox regression analysis was used to determine the most significant prognostic factor among the following variables: serum CA125 before surgery and after the first, second, and sixth cycles of chemotherapy; the nadir CA125 value; the relative percentage change in CA125 levels after the first and second cycles of chemotherapy compared to baseline CA125; CA125 half-life; time to nadir; and time to normalization of the CA125 level. Results The CA125 level after the first chemotherapy cycle was the most significant independent prognostic factor for overall survival (OS). Time to normalization (p=0.028) and relative percentage change between CA125 levels at baseline and after the first chemotherapy cycle (p=0.021) were additional independent prognostic factors in terms of OS. The CA125 level after the first chemotherapy cycle (p=0.001) and time to normalization (p<0.001) were identified as independent prognostic factors for progression free survival (PFS). Conclusion Among well-established CA125-related prognostic factors, serum CA125 levels after the first cycle of chemotherapy and time to normalization were the most significant prognostic factors for both OS and PFS. PMID:26996555

  1. Continuous infusion of low-dose doxorubicin, epirubicin and mitoxantrone in cancer chemotherapy: a review.

    PubMed

    Greidanus, J; Willemse, P H; Uges, D R; Oremus, E T; De Langen, Z J; De Vries, E G

    1988-12-01

    With the recent development of reliable portable pumps and safe venous access systems, continuous infusion of chemotherapeutic agents on an out-patient basis has become feasible. Advantages of continuous infusion are the long-term exposure of tumour cells to the drug and the fact that most toxic effects are reduced for doxorubicin, epirubicin and mitoxantrone due to elimination of the high peak plasma levels. Preliminary data for doxorubicin suggest that its antitumour activity is maintained. Pharmacokinetic studies with epirubicin and mitoxantrone showed a linear relationship between drug dose infused and the steady-state plasma level for these drugs. The area under the curve for leukocytes drug level was higher during continuous infusion than after an equitoxic bolus injection of epirubicin and mitoxantrone. Well-randomized clinical trials will be necessary to investigate the role of continuous infusion of antracyclines and mitoxantrone in cancer chemotherapy in the future. PMID:3062572

  2. Combined methotrexate and high-dose vincristine chemotherapy with radiation therapy for small cell bronchogenic carcinoma

    SciTech Connect

    Holoye, P.Y.; Libnoch, J.A.; Anderson, T.; Cox, J.D.; Byhardt, R.W.; Hoffmann, R.G.

    1985-04-01

    The addition of methotrexate to a previously described regimen of cyclophosphamide, Adriamycin (doxorubicin), and high-dose vincristine (VAC) was tested in 50 evaluable patients with small cell bronchogenic carcinoma. Prophylactic whole brain radiation therapy was given during the first chemotherapy course and consolidation radiation therapy was given to the mediastinum and primary site after achieving partial or complete remission. The addition of methotrexate did not improve the incidence of complete remission as compared to a previous regimen without it. The addition of radiation therapy improved the local control rate. The high-dose vincristine in this and a previous CAV study improved the incidence of complete remission in both limited and extensive disease presentation as compared with the authors previous experience and induced an acceptable and reversible neurotoxicity. Moderate dose consolidation radiotherapy to the lung primary and mediastinum was effective in improving local control. The distinction between limited and extensive disease was found to be vague, as 22% of the patients could be shifted from one group to the other depending on definition. The evaluation of the various staging procedures indicates that bone scan gave a small number of truly abnormal tests. Isotopic brain and liver-spleen scan could be duplicated by computerized axial tomography (CAT). CAT scan of abdomen disclosed unexpected extension to the retroperitoneal nodes and adrenals.

  3. A randomized phase III study evaluating the efficacy and safety of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy

    PubMed Central

    Aapro, M.; Rugo, H.; Rossi, G.; Rizzi, G.; Borroni, M. E.; Bondarenko, I.; Sarosiek, T.; Oprean, C.; Cardona-Huerta, S.; Lorusso, V.; Karthaus, M.; Schwartzberg, L.; Grunberg, S.

    2014-01-01

    Background Antiemetic guidelines recommend co-administration of agents that target multiple molecular pathways involved in emesis to maximize prevention and control of chemotherapy-induced nausea and vomiting (CINV). NEPA is a new oral fixed-dose combination of 300 mg netupitant, a highly selective NK1 receptor antagonist (RA) and 0.50 mg palonosetron (PALO), a pharmacologically and clinically distinct 5-HT3 RA, which targets dual antiemetic pathways. Patients and methods This multinational, randomized, double-blind, parallel group phase III study (NCT01339260) in 1455 chemotherapy-naïve patients receiving moderately emetogenic (anthracycline–cyclophosphamide) chemotherapy evaluated the efficacy and safety of a single oral dose of NEPA versus a single oral dose (0.50 mg) of PALO. All patients also received oral dexamethasone (DEX) on day 1 only (12 mg in the NEPA arm and 20 mg in the PALO arm). The primary efficacy end point was complete response (CR: no emesis, no rescue medication) during the delayed (25–120 h) phase in cycle 1. Results The percentage of patients with CR during the delayed phase was significantly higher in the NEPA group compared with the PALO group (76.9% versus 69.5%; P = 0.001), as were the percentages in the overall (0–120 h) (74.3% versus 66.6%; P = 0.001) and acute (0–24 h) (88.4% versus 85.0%; P = 0.047) phases. NEPA was also superior to PALO during the delayed and overall phases for all secondary efficacy end points of no emesis, no significant nausea and complete protection (CR plus no significant nausea). NEPA was well tolerated with a similar safety profile as PALO. Conclusions NEPA plus a single dose of DEX was superior to PALO plus DEX in preventing CINV following moderately emetogenic chemotherapy in acute, delayed and overall phases of observation. As a fixed-dose antiemetic drug combination, NEPA along with a single dose of DEX on day 1 offers guideline-based prophylaxis with a convenient, single-day treatment. PMID

  4. Radiation fosters dose-dependent and chemotherapy-induced immunogenic cell death

    PubMed Central

    Golden, Encouse B; Frances, Derek; Pellicciotta, Ilenia; Demaria, Sandra; Helen Barcellos-Hoff, Mary; Formenti, Silvia C

    2014-01-01

    Established tumors are typified by an immunosuppresive microenvironment. Countering this naturally occurring phenomenon, emerging evidence suggests that radiation promotes a proimmunogenic milieu within the tumor capable of stimulating host cancer-specific immune responses. Three cryptic immunogenic components of cytotoxic-agent induced cell death—namely, calreticulin cell surface exposure, the release of high mobility group box 1 (HMGB1) protein, and the liberation of ATP—have been previously shown to be critical for dendritic cell (DC) activation and effector T-cell priming. Thus, these immune-mobilizing components commonly presage tumor rejection in response to treatment. We initially set out to address the hypothesis that radiation-induced immunogenic cell death (ICD) is dose-dependent. Next, we hypothesized that radiation would enhance chemotherapy-induced ICD when given concomitantly, as suggested by the favorable clinical outcomes observed in response to analogous concurrent chemoradiation regimens. Thus, we designed an in vitro assay to examine the 3 hallmark features of ICD at clinically relevant doses of radiation. We then tested the immunogenic-death inducing effects of radiation combined with carboplatin or paclitaxel, focusing on these combinations to mimic chemoradiation regimens actually used in clinical trials of early stage triple negative [NCT0128953/NYU-10–01969] and locally advanced [NYU-06209] breast cancer patients, respectively. Despite the obvious limitations of an in vitro model, radiotherapy produced both a dose-dependent induction and chemotherapeutic enhancement of ICD. These findings provide preliminary evidence that ICD stimulated by either high-dose radiotherapy alone, or concurrent chemoradiation regimens, may contribute to the establishment of a peritumoral proimmunogenic milieu. PMID:25071979

  5. Different doses of prophylactic platelet transfusion for preventing bleeding in patients with haematological disorders after chemotherapy or stem cell transplantation

    PubMed Central

    Estcourt, Lise J; Stanworth, Simon; Doree, Carolyn; Trivella, Marialena; Hopewell, Sally; Murphy, Michael F; Tinmouth, Alan

    2014-01-01

    This is the protocol for a review and there is no abstract. The objectives are as follows: To determine whether different doses of prophylactic platelet transfusions (platelet transfusions given to prevent bleeding) affect their efficacy and safety in preventing bleeding in patients with haematological disorders after chemotherapy with or without stem cell transplantation. PMID:25722652

  6. Formulation and stability of busulfan for intravenous administration in high-dose chemotherapy.

    PubMed

    Bhagwatwar, H P; Phadungpojna, S; Chow, D S; Andersson, B S

    1996-01-01

    The bifunctional alkylating agent busulfan (Bu) was solubilized in a cosolvent mixture of anhydrous dimethylacetamide (DMA), polyethylene glycol 400 (PEG400), and water at a ratio of 1:2:2 (v/v/v), to achieve a Bu concentration of 3 mg/ml, a preparation that would be suitable for parenteral administration in high-dose chemotherapy preceding bone marrow transplantation. The complete formulation was stable for more than 54 h at room temperature (RT, 22 degrees C). An accelerated stability study of Bu in anhydrous DMA or DMA/PEG400 (1:2) as stock solutions indicated shelf-lives of 191 and 180 days respectively, at RT, and 8.2 and 7.5 years, respectively, at 4 degrees C. Although the complete formulation with Bu was very hypertonic, hemolysis studies indicated that the formulation would be safe for intravenous (i.v.) administration, since it would be rapidly diluted to harmless tonicity levels in the blood. Cytotoxicity studies of the complete formulation in vitro proved that Bu retained its activity when dissolved in the complete vehicle. A preliminary pharmacokinetic study in a rodent model after the i.v. administration of Bu at a dose of 1 mg/kg body weight yielded high plasma concentrations of Bu for at least 5 h after injection. PMID:8599861

  7. High-dose chemotherapy and autologous stem cell transplantation for relapsed or refractory nodular lymphocyte predominant Hodgkin lymphoma.

    PubMed

    Akhtar, S; Elhassan, T A M; Edesa, W; Rauf, M S; Zahir, M N; Maghfoor, I

    2016-01-01

    Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a distinct subtype of Hodgkin lymphoma. We report our results of relapsed/refractory NLPHL patients who received high-dose chemotherapy and autogenic stem cell transplantation (HDC auto-SCT). Seventeen NLPHL patients received HDC auto-SCT (1996–2014): male 14 and female 3, with median age at diagnosis of 22 years, at HDC auto-SCT 28 years (15–58 years). At the time of relapse/progression, 13 (76 %) had NLPHL and 4 (24 %) had transformed diffuse large B cell lymphoma. The reason for HDC auto-SCT was refractory NLPHL in 12 patients and relapsed in 5 patients. Salvage chemotherapy was etoposide, methylprednisolone, cisplatinum, and Ara-C (ESHAP); eight patients also received rituximab with ESHAP. HDC was carmustine, etoposide, cytarabine, and melphalan (BEAM). Post-auto-SCT, complete remission was achieved in 14 (82 %), partial remission in 1 (6 %), and progressive disease in 2 (12 %) patients. The median follow-up is 63 months from auto-SCT (6–124 months). Of the nine patients who received only ESHAP, four had post-auto-SCT events versus no event in all eight patients who received rituximab+ESHAP. Kaplan–Meier estimates of 5-year event-free survival for the whole group is 76 %: rituximab+salvage (100 %) versus salvage alone (56 %), P=0.041. Overall survival is 94 %: 100 versus 89 %, respectively, P=not significant (NS). Even in refractory NLPHL patients, long-term disease-free survival is possible after HDC auto-SCT. Post-auto-SCT relapse or progression can still be managed with chemo/chemo+immunotherapy/ radiation. These encouraging results of rituximab in salvage setting should be explored further in a clinical trial setting for this patient population. PMID:26467917

  8. Cure Rates in Small Cell and Non-Small Cell Carcinoma of the Lung Utilizing High-Dose Radiotherapy and Chemotherapy

    PubMed Central

    Akbiyik, Nejat; Alexander, Leslie L.

    1986-01-01

    From 1967 to 1977, 72 patients with small cell carcinoma of the lung were seen. Thirty-five of these patients had unilaterally localized lesions (limited disease) and were treated with cobalt 60 radiation therapy (6,000 rad in six weeks) followed by chemotherapy consisting of cyclophosphamide (Cytoxan), vincristine, methotrexate and lomustine (CCNU) (Group A). The remaining 37 patients with extensive disease were treated with similar chemotherapy alone, or in combination with local palliative radiotherapy to the symptomatic area (Group B). For Group A the five-year survival rate was 20 percent, while for both groups combined, it was only 5 percent. During this same period 560 patients with non-small cell carcinomas were treated. The five-year survival rate for those patients with operable, resectable lesions was 33 percent, while for those with unilateral, inoperable, unresectable lesions, it was 10 percent. Thus, it would appear that the results in limited small cell and non-small cell carcinomas of the lung utilizing high-dose radiotherapy followed by chemotherapy are comparable, and that limited small cell carcinoma of the lung patients with high-dose radiotherapy followed by chemotherapy can survive longer than those patients with stage III, non-small cell lung carcinoma. While the two- to five-year survival rates in small cell carcinoma demonstrate no appreciable differences, in non-small cell carcinomas there are significant two- to five-year survival differences. These improved results probably are due to the increased sensitivity of small cell carcinoma to high-dose local radiotherapy and to the chemotherapeutic vulnerability of circulating and microscopic metastatic cancer cells. PMID:3012100

  9. Recurrent adult choroid plexus carcinoma treated with high-dose chemotherapy and syngeneic stem cell (bone marrow) transplant.

    PubMed

    Samuel, Thomas A; Parikh, Jigarkumar; Sharma, Suash; Giller, Cole A; Sterling, Kristen; Kapoor, Suraj; Pirkle, Christen; Jillella, Anand

    2013-12-01

    Choroid plexus carcinomas (CPCs) are rare epithelial central nervous system tumors. CPC occurs mainly in infants and young children, comprising ≈ 1 to 4% of all pediatric brain neoplasms. There is very limited information available regarding tumor biology and CPC treatment due to its rarity. There have been various case reports and meta-analyses of reported cases with CPC. Surgical resection is often challenging but remains a well-established treatment option. Chemotherapy is often reserved for recurrent or refractory cases, but the goal of treatment is usually palliative. We present a case of recurrent, adult CPC with disseminated leptomeningeal involvement treated with salvage chemotherapy including high-dose ifosfamide, carboplatin, and etoposide; once a remission was achieved, this response was consolidated with a syngeneic stem cell (bone marrow) transplant after a preparative regimen of high-dose chemotherapy with carboplatin, etoposide, and thiotepa. Although the patient tolerated the transplant well and remained disease-free for 12 months, she subsequently succumbed to relapsed disease 18 months posttransplant. We believe that this is the first report of using syngeneic stem cell transplant in CPC to consolidate a remission achieved by salvage chemotherapy. PMID:23427033

  10. Role of Maintenance Therapy after High-Dose Chemotherapy and Autologous Hematopoietic Cell Transplantation in Aggressive Lymphomas: A Systematic Review.

    PubMed

    Taverna, Josephine A; Yun, Seongseok; Jonnadula, Jayasree; Saleh, Ahlam; Riaz, Irbaz Bin; Abraham, Ivo; Yeager, Andrew M; Persky, Daniel O; McBride, Ali; Haldar, Subrata; Anwer, Faiz

    2016-07-01

    Significant uncertainty exists in regard to the efficacy of maintenance therapy after high-dose chemotherapy (HDC) as well as autologous stem cell transplantation (ASCT) for the treatment of patients with aggressive lymphoma. A systematic review was performed to evaluate the effectiveness of post-ASCT maintenance therapy in patients with relapsed/refractory lymphoma. A comprehensive literature search yielded 4476 studies and a total of 42 studies (11 randomized controlled trials [RCT], 9 retrospective comparative studies, and 22 single-arm studies) were included in the systematic review. There was significant heterogeneity in study design, chemotherapeutic regimens, post-ASCT maintenance strategies, patient enrollment criteria, and study endpoints. Our findings suggest that post-ASCT maintenance immune-targeting strategies, including PD-1/PD-L1 blocking antibodies, rituximab, and brentuximab, may improve progression-free survival but not overall survival. Collectively, the results indicate a need for testing new strategies with well-designed and adequately powered RCTs to better address the role of post-ASCT maintenance in relapsed/refractory lymphomas. PMID:26899562

  11. Simultaneous bilateral spontaneous pneumothorax following high-dose chemotherapy and bone marrow transplantation for mantle cell lymphoma without evidence of pulmonary disease.

    PubMed

    Schneider, Ashley E; Talmon, Geoffrey A

    2010-12-01

    Simultaneous bilateral spontaneous pneumothorax (SBSP) during high-dose chemotherapy has been described in patients with pulmonary involvement by malignancy, including sarcoma, trophoblastic tumor, non-seminomatous testicular cancer, and non-Hodgkin lymphoma. We present a case of SBSP developing in a patient 11 days after a high-dose chemotherapy preparative regimen and stem cell transplantation without underlying pulmonary disease or evidence of lung lesions. It is important to recognize spontaneous pneumothorax as a potential complication of high-dose chemotherapy, especially in patients with known pulmonary lesions. PMID:20589405

  12. Phase II study of central nervous system (CNS)-directed chemotherapy including high-dose chemotherapy with autologous stem cell transplantation for CNS relapse of aggressive lymphomas

    PubMed Central

    Korfel, Agnieszka; Elter, Thomas; Thiel, Eckhard; Hänel, Matthias; Möhle, Robert; Schroers, Roland; Reiser, Marcel; Dreyling, Martin; Eucker, Jan; Scholz, Christian; Metzner, Bernd; Röth, Alexander; Birkmann, Josef; Schlegel, Uwe; Martus, Peter; Illerhaus, Gerard; Fischer, Lars

    2013-01-01

    The prognosis of patients with central nervous system relapse of aggressive lymphoma is very poor with no therapy established so far. In a prospective multicenter phase II study, we evaluated a potentially curative chemotherapy-only regimen in these patients. Adult immunocompetent patients 65 years of age or under received induction chemotherapy with MTX/IFO/DEP (methotrexate 4 g/m2 intravenously (i.v.) Day 1, ifosfamide 2 g/m2 i.v. Days 3– 5 and liposomal cytarabine 50 mg intrathecally (i.th) Day 6) and AraC/TT/DEP (cytarabine 3g/m2 i.v. Days 1–2, thiotepa 40 mg/m2 i.v. Day 2 and i.th. liposomal cytarabine 50 mg i.th. Day 3) followed by high-dose chemotherapy with carmustine 400 mg/m2 i.v. Day −5, thiotepa 2×5 mg/kg i.v. Days −4 to −3 and etoposide 150 mg/m2 i.v. Days −5 to −3, and autologous stem cell transplantation Day 0 (HD-ASCT). Thirty eligible patients (median age 58 years) were enrolled. After HD-ASCT (n=24), there was a complete remission in 15 (63%), partial remission in 2 (8%) and progressive disease in 7 (29%) patients. Myelotoxicity was the most adverse event with CTC grade 3/4 infections in 12% of MTX/IFO/DEP courses, 21% of AraC/TT/DEP courses and 46% of HD-ASCT courses. The 2-year time to treatment failure was 49%±19 for all patients and 58%±22 for patients completing HD-ASCT. The protocol assessed proved feasible and highly active with long-lasting remissions in a large proportion of patients. (ClinicalTrials.govIdentifier NCT01148173) PMID:23242601

  13. Phase II study of central nervous system (CNS)-directed chemotherapy including high-dose chemotherapy with autologous stem cell transplantation for CNS relapse of aggressive lymphomas.

    PubMed

    Korfel, Agnieszka; Elter, Thomas; Thiel, Eckhard; Hänel, Matthias; Möhle, Robert; Schroers, Roland; Reiser, Marcel; Dreyling, Martin; Eucker, Jan; Scholz, Christian; Metzner, Bernd; Röth, Alexander; Birkmann, Josef; Schlegel, Uwe; Martus, Peter; Illerhaus, Gerard; Fischer, Lars

    2013-03-01

    The prognosis of patients with central nervous system relapse of aggressive lymphoma is very poor with no therapy established so far. In a prospective multicenter phase II study, we evaluated a potentially curative chemotherapy-only regimen in these patients. Adult immunocompetent patients 65 years of age or under received induction chemotherapy with MTX/IFO/DEP (methotrexate 4 g/m(2) intravenously (i.v.) Day 1, ifosfamide 2 g/m(2) i.v. Days 3- 5 and liposomal cytarabine 50 mg intrathecally (i.th) Day 6) and AraC/TT/DEP (cytarabine 3g/m(2) i.v. Days 1-2, thiotepa 40 mg/m(2) i.v. Day 2 and i.th. liposomal cytarabine 50 mg i.th. Day 3) followed by high-dose chemotherapy with carmustine 400 mg/m(2) i.v. Day -5, thiotepa 2×5 mg/kg i.v. Days -4 to -3 and etoposide 150 mg/m(2) i.v. Days -5 to -3, and autologous stem cell transplantation Day 0 (HD-ASCT). Thirty eligible patients (median age 58 years) were enrolled. After HD-ASCT (n=24), there was a complete remission in 15 (63%), partial remission in 2 (8%) and progressive disease in 7 (29%) patients. Myelotoxicity was the most adverse event with CTC grade 3/4 infections in 12% of MTX/IFO/DEP courses, 21% of AraC/TT/DEP courses and 46% of HD-ASCT courses. The 2-year time to treatment failure was 49%±19 for all patients and 58%±22 for patients completing HD-ASCT. The protocol assessed proved feasible and highly active with long-lasting remissions in a large proportion of patients. (ClinicalTrials.govIdentifier NCT01148173). PMID:23242601

  14. Different doses of prophylactic platelet transfusion for preventing bleeding in people with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation

    PubMed Central

    Estcourt, Lise J; Stanworth, Simon; Doree, Carolyn; Trivella, Marialena; Hopewell, Sally; Blanco, Patricia; Murphy, Michael F

    2015-01-01

    methodological procedures expected by The Cochrane Collaboration. Main results We included seven trials (1814 participants) in this review; six were conducted during one course of treatment (chemotherapy or HSCT). Overall the methodological quality of studies was low to moderate across different outcomes according to GRADE methodology. None of the included studies were at low risk of bias in every domain, and all the included studies had some threats to validity. Five studies reported the number of participants with at least one clinically significant bleeding episode within 30 days from the start of the study. There was no difference in the number of participants with a clinically significant bleeding episode between the low-dose and standard-dose groups (four studies; 1170 participants; risk ratio (RR) 1.04, 95% confidence interval (CI) 0.95 to 1.13; moderate-quality evidence); low-dose and high-dose groups (one study; 849 participants; RR 1.02, 95% CI 0.93 to 1.11; moderate-quality evidence); or high-dose and standard-dose groups (two studies; 951 participants; RR 1.02, 95% CI 0.93 to 1.11; moderate-quality evidence). Three studies reported the number of days with a clinically significant bleeding event per participant. There was no difference in the number of days of bleeding per participant between the low-dose and standard-dose groups (two studies; 230 participants; mean difference −0.17, 95% CI −0.51 to 0.17; low quality evidence). One study (855 participants) showed no difference in the number of days of bleeding per participant between high-dose and standard-dose groups, or between low-dose and high-dose groups (849 participants). Three studies reported the number of participants with severe or life-threatening bleeding. There was no difference in the number of participants with severe or life-threatening bleeding between a low-dose and a standard-dose platelet transfusion policy (three studies; 1059 participants; RR 1.33, 95% CI 0.91 to 1.92; low-quality evidence

  15. High-dose chemotherapy and autologous stem cell support followed by posttransplantation doxorubicin as initial therapy for metastatic breast cancer.

    PubMed

    deMagalhaes-Silverman, M; Bloom, E; Lembersky, B; Lister, J; Pincus, S; Rybka, W; Voloshin, M; Wilson, J; Ball, E

    1997-02-01

    High-dose chemotherapy is associated with a high complete response rate and possibly some survival advantage in patients with metastatic breast cancer. We designed a clinical trial consisting of a two-step high-dose chemotherapy regimen followed by posttransplantation doxorubicin as the first chemotherapy treatment for metastatic disease. Twenty-one patients with metastatic breast cancer and no previous chemotherapy for metastatic disease were treated with high-dose cyclophosphamide (Cy; 5000 mg/m2), followed by granulocyte colony-stimulating factor. Peripheral blood stem cells were collected. Subsequently, patients received Cy (6000 mg/m2), thiotepa (500 mg/m2), and carboplatin (800 mg/m2) (CTCb) with hematopoietic rescue. Upon recovery of hematopoietic and gastrointestinal toxicity, three cycles of doxorubicin (Dox; 60 mg/m2) were delivered. After Cy, nine patients (45%) developed neutropenic fevers. There were no episodes of bacteremia. Patients received CTCb 37 days after starting Cy and had a hospital stay of 19 days. After CTCb, the median number of days to an absolute neutrophil count >5 x 10(9)/liter was 8, and the median number of days to a platelet count >20 x 10(9)/liter was 9. Neutropenic fevers occurred in 12 patients. There were no hemorrhagic complications. Fifty-five of the 63 planned courses of Dox were delivered. The median time from peripheral blood stem cell infusion to the first Dox cycle was 38 days. The median time to the second Dox cycle was 28 days, and to the last cycle was 30 days. Three episodes of neutropenic fevers were observed. Two patients developed herpes zoster. This regimen is feasible, with acceptable toxicity. PMID:9815672

  16. Parathyroid hormone linked to a collagen binding domain promotes hair growth in a mouse model of chemotherapy-induced alopecia in a dose-dependent manner.

    PubMed

    Katikaneni, Ranjitha; Ponnapakkam, Tulasi; Seymour, Andrew; Sakon, Joshua; Gensure, Robert

    2014-08-01

    Chemotherapy-induced alopecia is a major source of psychological stress in patients undergoing cancer chemotherapy, and it can influence treatment decisions. Although there is currently no therapy for alopecia, a fusion protein of parathyroid hormone and collagen binding domain (PTH-CBD) has shown promise in animal models. The aim of this study was to determine whether there are dose-dependent effects of PTH-CBD on chemotherapy-induced alopecia in a mouse model. C57BL/6J mice were waxed to synchronize hair follicles; treated on day 7 with vehicle or PTH-CBD (100, 320, and 1000 mcg/kg subcutaneous injection); and treated on day 9 with vehicle or cyclophosphamide (150 mg/kg intraperitoneally). Mice were photographed every 3-4 days and killed on day 63 for histological analysis. Photographs were quantified by gray scale analysis to assess hair content. Mice not receiving chemotherapy showed regrowth of hair 2 weeks after waxing and normal histology after 2 months. Mice receiving chemotherapy alone showed marked hair loss after chemotherapy, which was sustained for 10 days and was followed by rapid regrowth of a normal coat. Histological analysis revealed rapid cycling dystrophic anagen/catagen follicles. Animals receiving chemotherapy and PTH-CBD showed decreased hair loss and more rapid regrowth of hair than that seen with chemotherapy alone (increased hair growth by gray scale analysis, P<0.05), and the effects were dose dependent. Histologically, hair follicles in animals receiving the highest dose of PTH-CBD were in a quiescent phase, similar to that in mice that did not receive chemotherapy. Single-dose subcutaneous administration of PTH-CBD showed dose-dependent effects in minimizing hair loss and speeding up recovery from chemotherapy-induced alopecia. PMID:24710191

  17. Review of oral fixed-dose combination netupitant and palonosetron (NEPA) for the treatment of chemotherapy-induced nausea and vomiting.

    PubMed

    Lorusso, Vito; Karthaus, Meinolf; Aapro, Matti

    2015-01-01

    Current guidelines recommend the combination of a neurokinin-1 (NK1) receptor antagonist (RA) and a 5-hydroxytryptamine-3 (5-HT3) RA, together with corticosteroids, in order to prevent chemotherapy-induced nausea and vomiting with anthracycline-cyclophosphamide and highly emetogenic chemotherapy, and it is to be considered with moderately emetogenic chemotherapy. Netupitant and palonosetron (NEPA) is a fixed-dose combination of netupitant, a novel, highly selective NK1 RA, and palonosetron, a new-generation 5-HT3 RA, targeting two major emetic pathways in a single oral capsule. In clinical trials, NEPA administered on day 1 together with dexamethasone was highly effective and well tolerated in the prevention of chemotherapy-induced nausea and vomiting in patients with solid tumors undergoing moderately emetogenic chemotherapy or highly emetogenic chemotherapy. NEPA offers maximal convenience, and as a simple guideline-based regimen, has the potential to improve adherence to guidelines. PMID:25360998

  18. Proposed strategy for the use of high-dose chemotherapy with stem cell rescue and intrathecal topotecan without whole-brain irradiation for infantile classic medulloblastoma.

    PubMed

    Yamada, Ai; Moritake, Hiroshi; Kamimura, Sachiyo; Yamashita, Shinji; Takeshima, Hideo; Nunoi, Hiroyuki

    2014-12-01

    We describe a 6-month-old infant with classic medulloblastoma. Gross total resection of the left cerebellar tumor was performed; however, relapse occurred during the administration of intrathecal and intravenous methotrexate-based chemotherapy. After undergoing resection, high-dose chemotherapy was administered consisting of topotecan, melphalan, and cyclophosphamide with autologous peripheral stem cell rescue followed by local irradiation and intrathecal topotecan, which resulted in a complete response for more than two years. The administration of high-dose chemotherapy followed by intrathecal topotecan as maintenance therapy is an effective strategy, without losses in the cognitive function, for avoiding the use of whole-brain irradiation for infantile classic medulloblastoma. PMID:25174961

  19. Prognostic impact of progression to induction chemotherapy and prior paclitaxel therapy in patients with germ cell tumors receiving salvage high-dose chemotherapy in the last 10 years: a study of the European Society for Blood and Marrow Transplantation Solid Tumors Working Party.

    PubMed

    Necchi, A; Miceli, R; Bregni, M; Bokemeyer, C; Berger, L A; Oechsle, K; Schumacher, K; Kanfer, E; Bourhis, J H; Massard, C; Laszlo, D; Montoro, J; Flechon, A; Arpaci, F; Secondino, S; Wuchter, P; Dreger, P; Crysandt, M; Worel, N; Kruger, W; Ringhoffer, M; Unal, A; Nagler, A; Campos, A; Wahlin, A; Michieli, M; Sucak, G; Donnini, I; Schots, R; Ifrah, N; Badoglio, M; Martino, M; Raggi, D; Giannatempo, P; Rosti, G; Pedrazzoli, P; Lanza, F

    2016-03-01

    Little is known about the prognostic impact of prior paclitaxel therapy and response to induction chemotherapy defined as the regimen preceding high-dose chemotherapy (HDCT) for the salvage therapy of advanced germ cell tumors. Twenty European Society for Blood and Marrow Transplantation centers contributed data on patients treated between 2002 and 2012. Paclitaxel used in either prior lines of therapy or in induction-mobilization regimens was considered. Multivariable Cox analyses of prespecified factors were undertaken on PFS and overall survival (OS). As of October 2013, data for 324 patients had been contributed to this study. One hundred and ninety-two patients (59.3%) had received paclitaxel. Sixty-one patients (19%) had a progression to induction chemotherapy, 234 (72%) a response (29 (9%) missing or granulocyte colony-stimulating factor without chemotherapy). Both progression to induction chemotherapy and prior paclitaxel were significantly associated with shorter OS univariably (P<0.001 and P=0.032). On multivariable analysis from the model with fully available data (N=216) progression to induction was significantly prognostic for PFS and OS (P=0.003), but prior paclitaxel was not (P=0.674 and P=0.739). These results were confirmed after multiple imputation of missing data. Progression to induction chemotherapy could be demonstrated as an independent prognostic factor, in contrast to prior paclitaxel. PMID:26642334

  20. Phase I Dose-Escalation Study of Docetaxel, Cisplatin, and 5-Fluorouracil Combination Chemotherapy in Patients With Advanced Esophageal Carcinoma

    PubMed Central

    Satomura, Hitoshi; Nakajima, Masanobu; Sasaki, Kinro; Yamaguchi, Satoru; Domeki, Yasushi; Takahashi, Masakazu; Muroi, Hiroto; Kubo, Tsukasa; Kikuchi, Maiko; Otomo, Haruka; Ihara, Keisuke; Kato, Hiroyuki

    2015-01-01

    A dose-escalation study of docetaxel (DOC), cisplatin (CDDP), and 5-fluorouracil (5-FU; DCF combination regimen) was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD) and dose-limiting toxicities (DLT) in advanced esophageal carcinoma. Eighteen patients with esophageal carcinoma were enrolled and received DCF combination therapy at different dose levels. DLTs included febrile neutropenia and oral mucositis. DLT occurred in 2 out of 6 patients at level 2 and 3. The study proceeded to level 4, according to the protocol. The level 4 dose was defined as the MTD and the level 3 dose was defined as the RD. The RD for DCF combination chemotherapy for advanced esophageal carcinoma in the present study was 70 mg/m2 DOC plus 70 mg/m2 CDDP on day 1 plus 700 mg/m2 5-FU on days 1–5 at 4-week intervals. This regimen was tolerable and highly active. A phase II study has been started. PMID:26414837

  1. Neoadjuvant dose-dense chemotherapy for locally advanced breast cancer: a meta-analysis of published studies.

    PubMed

    Petrelli, Fausto; Coinu, Andrea; Lonati, Veronica; Cabiddu, Mary; Ghilardi, Mara; Borgonovo, Karen; Barni, Sandro

    2016-08-01

    Large operable or locally advanced breast cancers (BCs) are usually treated with neoadjuvant chemotherapy (CT) before surgery. However, there is no evidence to support an improvement in efficacy with dose-dense (DD) CT in this setting. We, therefore, carried out a meta-analysis to investigate whether DD-CT was more effective than the reference (every 3 weeks anthracyclines±taxanes) standard-dose CT as neoadjuvant treatment for BC. We searched Pubmed, SCOPUS, EMBASE, the Web of Science, CINAHL, and the Cochrane Central Register of Controlled Trials for randomized trials comparing conventional versus DD neoadjuvant CT for BC. Odds ratios (ORs) for pathologic complete responses (ypT0N0M0: pCR) and hazard ratios (HRs) of death and recurrence [overall survival (OS), and disease-free survival (DFS)] were estimated and pooled. A QUADAS-2 report for all studies included in the final analysis was tabulated for the risk of bias and applicability. A total of six randomized trials fulfilled the inclusion criteria. The pooled rates of the pCR were 13.5 and 9.2% in the experimental and control arms. A significant increase in the pCR [OR=1.55, 95% confidence interval (CI) 1.18-2.02, P=0.001] was noted with neoadjuvant DD-CT. However, the patients who received DD-CT did not have significantly better DFS and OS rates (DFS: HR=0.88, 95% CI 0.76-1.01, P=0.06; OS: HR=0.89, 95% CI 0.78-1.02, P=0.08). Even with the limitation of a relatively short follow-up period, this meta-analysis shows that DD neoadjuvant CT, despite not leading to a significant increase in survival, increases by 46.7% the possibility of achieving a pCR in operable and locally advanced BC. This treatment should thus be considered one of the backbone treatments of choice when neoadjuvant therapy is planned. PMID:27058707

  2. Dose-intensified CHOP with rituximab (R-Double-CHOP) followed by consolidation high-dose chemotherapies for patients with advanced diffuse large B-cell lymphoma.

    PubMed

    Kurita, Daisuke; Miura, Katsuhiro; Nakagawa, Masaru; Ohtake, Shimon; Sakagami, Masashi; Uchino, Yoshihito; Takahashi, Hiromichi; Kiso, Satomi; Hojo, Atsuko; Kodaira, Hitomi; Yagi, Mai; Hirabayashi, Yukio; Kobayashi, Yujin; Iriyama, Noriyoshi; Kobayashi, Sumiko; Hatta, Yoshihiro; Kura, Yoshimasa; Sugitani, Masahiko; Takei, Masami

    2015-06-01

    Even after the advent of rituximab, clinical outcomes of conventional immuno-chemotherapy for high-risk diffuse large B-cell lymphoma (DLBCL) remain unsatisfactory. We retrospectively evaluated the efficacy and safety of R-Double-CHOP (R-D-CHOP), consisting of rituximab (375 mg/m(2), day -2), cyclophosphamide (750 mg/m(2), day 1, 2), doxorubicin (50 mg/m(2), day 1, 2), vincristine [1.4 mg/m(2) (maximum 2.0 mg/body), day 1], and prednisolone (50 mg/m(2), day 1-5), followed by consolidation high-dose chemotherapy. This treatment was given to 51 de novo DLBCL patients with a median age of 54 (range 19-65), who were categorized as high/high-intermediate risk by the age-adjusted International Prognostic Index. Treatment was given every 3 weeks up to three courses. The overall response and the complete response rate for R-D-CHOP were 94 and 78 %, respectively. A total of 30 responders proceeded to high-dose chemotherapy followed by autologous stem cell transplantation (HDC/ASCT), whereas 16 received high-dose methotrexate (HD-MTX) alternatively. The 3-year overall survival and the event-free survival for all patients were 78 and 61 %, respectively. Major adverse events included hematological toxicities, but there were no treatment-related deaths during the observation period. We conclude that the R-D-CHOP regimen followed by HDC/ASCT or HD-MTX is a promising treatment option for younger patients with highly advanced DLBCL. PMID:25776837

  3. Reduced cerebral glucose metabolism and increased brain capillary permeability following high-dose methotrexate chemotherapy: a positron emission tomographic study

    SciTech Connect

    Phillips, P.C.; Dhawan, V.; Strother, S.C.; Sidtis, J.J.; Evans, A.C.; Allen, J.C.; Rottenberg, D.A.

    1987-01-01

    Regional glucose metabolic rate constants and blood-to-brain transport of rubidium were estimated using positron emission tomography in an adolescent patient with a brain tumor, before and after chemotherapy with intravenous high-dose methotrexate. Widespread depression of cerebral glucose metabolism was apparent 24 hours after drug administration, which may reflect reduced glucose phosphorylation, and the influx rate constant for /sup 82/Rb was increased, indicating a drug-induced alteration in blood-brain barrier function. Associated changes in neuropsychological performance, electroencephalogram, and plasma amino acid concentration were identified in the absence of evidence of systemic methotrexate toxicity, suggesting primary methotrexate neurotoxicity.

  4. Stage 4 neuroblastoma: sequential hemi-body irradiation or high-dose chemotherapy plus autologous haemopoietic stem cell transplantation to consolidate primary treatment

    PubMed Central

    Luksch, R; Podda, M; Gandola, L; Polastri, D; Piva, L; Castellani, R; Collini, P; Massimino, M; Cefalo, G; Terenziani, M; Ferrari, A; Casanova, M; Spreafico, F; Meazza, C; Bozzi, F; Marchianò, A; Ravagnani, F; Fossati-Bellani, F

    2005-01-01

    The aim of the present study was to evaluate the effectiveness of two consecutive nonrandomised treatment programs applied between 1989 and 1999 at the Istituto Nazionale Tumori of Milan in an unselected cohort of 59 children over the age of one with stage 4 neuroblastoma. Both treatment programs consisted of two phases, the induction of the remission phase and the consolidation phase. The induction of the remission phase consisted of intensive chemotherapy, and remained the same throughout the study period. The consolidation phase consisted of sequential hemi-body irradiation (HBI) (10 Gy per session, 6 weeks apart) in the first period (1988–June 1994) and sequential high-dose cyclophosphamide, etoposide, mitoxantrone+L-PAM and autologous haemopoietic stem cell transplantation in the second (July 1994–1999). Intention-to-treat analysis revealed a significantly better outcome for patients treated with the second program, the 5-year event-free survival probability being 0.12 for program 1 and 0.31 for program 2 (P=0.03). This finding led us to conclude that sequential HBI is useless as consolidation treatment. The high-dose chemotherapy adopted in the second program enabled a proportion of patients to obtain long-term survival but, since the clinical results remain unsatisfactory, new treatment strategies are warranted. PMID:15900298

  5. A study to investigate dose escalation of doxorubicin in ABVD chemotherapy for Hodgkin lymphoma incorporating biomarkers of response and toxicity

    PubMed Central

    Gibb, A; Greystoke, A; Ranson, M; Linton, K; Neeson, S; Hampson, G; Illidge, T; Smith, E; Dive, C; Pettitt, A; Lister, A; Johnson, P; Radford, J

    2013-01-01

    Background: Myelotoxicity during initial cycles of chemotherapy for Hodgkin lymphoma is associated with better outcome, supporting the concept of individualised dosing based on pharmacodynamic end points to optimise results. This study was performed to identify the maximum tolerated dose (MTD) of doxorubicin within cycles 1–3 ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine). Circulating biomarkers of response (nucleosomal DNA, nDNA) and epithelial toxicity (Cytokeratin 18, CK18) were also measured. Methods: Dose escalation of doxorubicin in cycles 1–3 ABVD supported by pegfilgrastim was performed on a six-patient cohort basis (35, 45 and 55 mg m–2) with doxorubicin reduced to 25 mg m–2 or omitted in cycles 4–6 to maintain cumulative exposure of 103–130% standard ABVD. BVD was given at standard doses throughout. Six additional subjects were recruited at the MTD. Results: Twenty-four subjects were recruited. Dose-limiting toxicities (DLTs) of grade 3 neuropathy, pneumonitis, palmar-plantar erythema and neutropenic infection were observed at 55 mg m–2, so 45 mg m–2 was declared the MTD. In patients who subsequently experienced DLT at any time, large increases in CK18 were seen on day 3 of cycle 1 ABVD. Conclusion: Escalated ABVD incorporating doxorubicin at 45 mg m–2 in cycles 1–3 can be delivered safely with pegfilgrastim support. Circulating cell death biomarkers may assist in the development of future individualised dosing strategies. PMID:24136151

  6. Female fertility following dose-adjusted EPOCH-R chemotherapy in primary mediastinal B-cell lymphomas.

    PubMed

    Gharwan, Helen; Lai, Catherine; Grant, Cliona; Dunleavy, Kieron; Steinberg, Seth M; Shovlin, Margaret; Fojo, Tito; Wilson, Wyndham H

    2016-07-01

    We assessed fertility/gonadal function in premenopausal women treated with dose-adjusted EPOCH-Rituximab for untreated primary mediastinal B-cell lymphoma (PMBL). Eligible patents were ≤ 50 years and premenopausal. Serial reproductive histories were obtained and hormonal assays were performed on serum samples before, at the end of treatment and 4-18 months later. Twenty-eight eligible women had a median age (range) of 31 (21-50) years and were followed a median of 7.3 years. Of 23 patients who completed a questionnaire, 19 (83%) were and four were not menstruating prior to chemotherapy. Amenorrhea developed in 12 patients during chemotherapy. At > 1-year follow-up, 14/19 (74%) patients were menstruating, all < 35 years old, and six (43%) of these patients delivered healthy children. Hormonal assays showed ovarian dysfunction during chemotherapy in all patients with varying recovery at 4-18 months after treatment. Fertility was preserved in most women with ovarian failure confined to patients > 40 years old. PMID:27183887

  7. Neutrophil-guided dosing of anthracycline-cyclophosphamide-containing chemotherapy in patients with breast cancer: a feasibility study.

    PubMed

    Drooger, Jan C; van Pelt-Sprangers, Johanna M; Leunis, Corry; Jager, Agnes; de Jongh, Felix E

    2015-04-01

    The aim of this study was to investigate whether neutrophil-guided dose escalation of anthracycline-cyclophosphamide-containing chemotherapy (ACC) for breast cancer is feasible, in order to optimize outcome. Breast cancer patients planned for 3-weekly ACC were enrolled in this study. The first treatment cycle was administered in a standard BSA-adjusted dose. The absolute neutrophil count was measured at baseline and at day 8, 11 and 15 after administration of ACC. For patients with none or mild (CTC grade 0-2) neutropenia and no other dose-limiting toxicity, we performed a 10-25 % dose escalation of the second cycle with the opportunity to a further 10-25 % dose escalation of the third cycle. Thirty patients were treated in the adjuvant setting with either FE100C (n = 23) or AC (n = 4), or in the palliative setting with FAC (n = 3). Two out of 23 patients (9 %) treated with FEC did not develop grade 3-4 neutropenia after the first treatment cycle. Dose escalation was performed in these two patients (30 % in one and 15 % in the other patient). During dose escalation, there were no complications like febrile neutropenia. No patients treated with FAC or AC could be escalated, since all of them developed grade 3-4 neutropenia. We conclude that asymptomatic grade 3-4 neutropenia is likely to be achieved in the majority of patients with breast cancer treated with ACC according to presently advocated BSA-based dose levels. Escalation of currently advocated ACC doses without G-CSF, with a target of grade 3-4 neutropenia, is feasible, but only possible in a small proportion of patients. EudraCT 2010-020309-33. PMID:25772511

  8. IMRT may increase pneumonitis risk relative to 3D-CRT in patients receiving combined chemotherapy and radiation therapy: a modeling study of dose dumping

    PubMed Central

    Vogelius, Ivan S.; Westerly, David C.; Cannon, George M.; Mackie, Thomas R.; Mehta, Minesh P.; Sugie, Chikao; Bentzen, Søren M.

    2011-01-01

    Purpose To model the possible interaction between cytotoxic chemotherapy and radiation dose distribution with respect to the risk of radiation pneumonitis (RP). Methods and materials Eighteen non-small cell lung cancer patients previously treated with helical tomotherapy at the University of Wisconsin were selected for this modeling study. Three treatment plans were considered in the study: (1) the delivered tomotherapy plans; (2) a 3D conformal radiotherapy (3D-CRT) plan; and (3) a fixed field intensity modulated radiotherapy (IMRT) plan. The IMRT and 3D-CRT plans were generated specifically for this study. Plans were optimized without adjusting for the chemotherapy effect. The effect of chemotherapy was modeled as an independent cell killing process by considering a uniform chemotherapy equivalent radiation dose (CERD) added to all voxels of the organ at risk. Risk of radiation pneumonitis was estimated for all plans using the Lyman and the Critical Volume models. Results For radiation therapy alone, the Critical Volume model predicts that the two IMRT plans are associated with a lower risk of RP than the 3D-CRT plan. However, when the CERD exceeds a certain threshold, the RP risk after IMRT is higher than after 3D-CRT. This threshold dose is in the range estimated from clinical chemo-radiation data sets. Conclusions Cytotoxic chemotherapy may affect the relative merit of competing radiation therapy plans. More work is needed to improve our understanding of the interaction between chemotherapy and radiation dose distribution in clinical settings. PMID:21477946

  9. Mutation of Escherichia coli cytosine deaminase significantly enhances molecular chemotherapy of human glioma.

    PubMed

    Kaliberov, S A; Market, J M; Gillespie, G Y; Krendelchtchikova, V; Della Manna, D; Sellers, J C; Kaliberova, L N; Black, M E; Buchsbaum, D J

    2007-07-01

    Combined treatment using adenoviral (Ad)-directed enzyme/prodrug therapy and radiation therapy has the potential to become a powerful method of cancer therapy. We have developed an Ad vector encoding a mutant bacterial cytosine deaminase (bCD) gene (AdbCD-D314A), which has a higher affinity for cytosine than wild-type bCD (bCDwt). The purpose of this study was to evaluate cytotoxicity in vitro and therapeutic efficacy in vivo of the combination of AdbCD-D314A with the prodrug 5-fluorocytosine (5-FC) and ionizing radiation against human glioma. The present study demonstrates that AdbCD-D314A infection resulted in increased 5-FC-mediated cell killing, compared with AdbCDwt. Furthermore, a significant increase in cytotoxicity following AdbCD-D314A and radiation treatment of glioma cells in vitro was demonstrated as compared to AdbCDwt. Animal studies showed significant inhibition of subcutaneous or intracranial tumor growth of D54MG glioma xenografts by the combination of AdbCD-D314A/5-FC with ionizing radiation as compared with either agent alone, and with AdbCDwt/5-FC plus radiation. The results suggest that the combination of AdbCD-D314A/5-FC with radiation produces markedly increased cytotoxic effects in cancer cells in vitro and in vivo. These data indicate that combined treatment with this novel mutant enzyme/prodrug therapy and radiotherapy provides a promising approach for cancer therapy. PMID:17495948

  10. High-dose chemotherapy and autologous bone marrow transplant in relapsed Hodgkin's disease--a pragmatic prognostic index.

    PubMed Central

    O'Brien, M. E.; Milan, S.; Cunningham, D.; Jones, A. L.; Nicolson, M.; Selby, P.; Hickish, T.; Hill, M.; Gore, M. E.; Viner, C.

    1996-01-01

    High-dose chemotherapy with autologous bone marrow transplantation is used in the treatment of relapsed or high-risk Hodgkin's disease. As prospective randomised studies have proved difficult to accrue to, current recommendations are based on the reports of large series of prospectively collected data. We have looked at the outcome of 89 patients treated in this way at a single institution and have developed an index to predict outcome. Of 89 patients, with a median age of 29 years (range 15-51 years), eight patients were in first complete remission/partial remission (CR/PR), 17 in second or later CR, 37 were responding relapses, 13 resistant relapses, 11 primary refractory and three untested relapses. Combinations of melphalan, BCNU and etoposide were given in all cases except in ten patients who received melphalan alone. The median follow-up was 43 months (range 6-77 months). A total of 24 patients were in CR at the time of autologous bone marrow transplantation (ABMT), 33 achieved CR with ABMT, 16 PR, to give a response rate to ABMT of 49/65 = 74% (95% CI 60-83%) with a CR rate of 51% (CI 36-62%). In a Cox's multivariate analysis the most important factors in predicting outcome after ABMT were response to treatment before entry, number of previous treatments and previous chemosensitivity. Using these factors we devised a prognostic index which reliably selects a group of patients (65%) with at least a 70% chance of being progression free from 1 year onwards. Patients who have never achieved a CR and have received three or more chemotherapy regimens do not benefit from high-dose chemotherapy as used in this study. PMID:8630292

  11. Dose intensity and toxicity associated with Taxotere formulation: a retrospective study in a population of breast cancer patients treated with docetaxel as an adjuvant or neoadjuvant chemotherapy.

    PubMed

    Chanat, Cédric; Delbaldo, Catherine; Denis, Jennifer; Bocaccio, François; Cojean-Zelek, Isabelle; Le Guyader, Nathalie

    2015-10-01

    Docetaxel is an antineoplastic drug from the taxane family that inhibits tubulin polymerization. Its brand name is Taxotere. In mid-2010, the formulation of Taxotere changed from a two-vial preparation needing a predilution (T2V) to a one-vial ready-to-use preparation (T1V). The aim of this study was to compare the toxicity profile of these two formulations. This retrospective observational and monocentric study included all patients who received Taxotere-based chemotherapy (100 mg/m) as an adjuvant or a neoadjuvant treatment for localized breast cancer, following initial treatment with anthracycline-based chemotherapy. Patients received either T2V or T1V Taxotere depending on the period of treatment. The main endpoint was the ratio of the dose of Taxotere received to that scheduled (R=docetaxel dose received/docetaxel dose scheduled). The secondary endpoint was tolerance. A total of 97 patients were included: 39 in the T2V group and 58 in the T1V group. The ratio of docetaxel received/docetaxel scheduled was significantly lower in the T1V than in the T2V group (0.83 vs. 0.95, respectively; P=0.028). A higher proportion of patients did not receive the totality of the scheduled dose in the T1V than in the T2V group (28 vs. 8%, respectively; P=0.03). Furthermore, the proportion of patients experiencing cutaneous toxicity was significantly higher in the T1V than in the T2V group (50 vs. 15%, respectively; P<0.001) as well as for neurological toxicity (31 vs. 15%, respectively; P=0.03). The frequency of grade 3 toxicities was higher in the T1V than in the T2V group (50 vs. 8%, P=0.016). The frequency of idiosyncratic toxicities was not affected by the change of formulation (4.7 vs. 5.4%, P=0.98). This study shows that patients treated with the T1V formulation received a significantly smaller dose of Taxotere than patients treated with T2V. In this small retrospective study, no conclusions can be drawn as to why a change in formulation would be associated with

  12. Dose Escalation of Total Marrow Irradiation With Concurrent Chemotherapy in Patients With Advanced Acute Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation

    SciTech Connect

    Wong, Jeffrey Y.C.; Forman, Stephen; Somlo, George; Liu An; Schultheiss, Timothy; Radany, Eric; Palmer, Joycelynne; Stein, Anthony

    2013-01-01

    Purpose: We have demonstrated that toxicities are acceptable with total marrow irradiation (TMI) at 16 Gy without chemotherapy or TMI at 12 Gy and the reduced intensity regimen of fludarabine/melphalan in patients undergoing hematopoietic cell transplantation (HCT). This article reports results of a study of TMI combined with higher intensity chemotherapy regimens in 2 phase I trials in patients with advanced acute myelogenous leukemia or acute lymphoblastic leukemia (AML/ALL) who would do poorly on standard intent-to-cure HCT regimens. Methods and Materials: Trial 1 consisted of TMI on Days -10 to -6, etoposide (VP16) on Day -5 (60 mg/kg), and cyclophosphamide (CY) on Day -3 (100 mg/kg). TMI dose was 12 (n=3 patients), 13.5 (n=3 patients), and 15 (n=6 patients) Gy at 1.5 Gy twice daily. Trial 2 consisted of busulfan (BU) on Days -12 to -8 (800 {mu}M min), TMI on Days -8 to -4, and VP16 on Day -3 (30 mg/kg). TMI dose was 12 (n=18) and 13.5 (n=2) Gy at 1.5 Gy twice daily. Results: Trial 1 had 12 patients with a median age of 33 years. Six patients had induction failures (IF), and 6 had first relapses (1RL), 9 with leukemia blast involvement of bone marrow ranging from 10%-98%, 5 with circulating blasts (24%-85%), and 2 with chloromas. No dose-limiting toxicities were observed. Eleven patients achieved complete remission at Day 30. With a median follow-up of 14.75 months, 5 patients remained in complete remission from 13.5-37.7 months. Trial 2 had 20 patients with a median age of 41 years. Thirteen patients had IF, and 5 had 1RL, 2 in second relapse, 19 with marrow blasts (3%-100%) and 13 with peripheral blasts (6%-63%). Grade 4 dose-limiting toxicities were seen at 13.5 Gy (stomatitis and hepatotoxicity). Stomatitis was the most frequent toxicity in both trials. Conclusions: TMI dose escalation to 15 Gy is possible when combined with CY/VP16 and is associated with acceptable toxicities and encouraging outcomes. TMI dose escalation is not possible with BU/VP16 due to

  13. Evolving concepts in the management of drug resistant ovarian cancer: dose dense chemotherapy and the reversal of clinical platinum resistance.

    PubMed

    Pinato, David J; Graham, Janet; Gabra, Hani; Sharma, Rohini

    2013-04-01

    Despite the initially high response rate to standard front-line debulking surgery followed by platinum-based chemotherapy, the relapse rate in ovarian cancer is high and many patients will recur within 6 months of completing platinum based treatment. These patients may still require further chemotherapy despite being considered "platinum resistant". In this setting, response rates to conventionally scheduled second line platinum and non-platinum agents is low, ranging between 5% and 15%. There is an emerging body of evidence that in this scenario, chemotherapeutic activity can be enhanced using unconventionally scheduled "dose-dense" platinum and non-platinum based regimens with improved response rates of up to 65%. Randomised studies to evaluate the impact of this approach on survival in recurrent, platinum resistant disease are urgently required to confirm the promising phase II findings if there is to be a change in the standard of care of patients with platinum resistant disease. In this review we discuss the evolving strategies to overcome resistance in patients with platinum resistant ovarian cancer with a particular focus on alterations in dose schedule as a means of reversing platinum resistance. PMID:22595680

  14. DAFODIL: A novel liposome-encapsulated synergistic combination of doxorubicin and 5FU for low dose chemotherapy.

    PubMed

    Camacho, Kathryn M; Menegatti, Stefano; Vogus, Douglas R; Pusuluri, Anusha; Fuchs, Zoë; Jarvis, Maria; Zakrewsky, Michael; Evans, Michael A; Chen, Renwei; Mitragotri, Samir

    2016-05-10

    PEGylated liposomes have transformed chemotherapeutic use of doxorubicin by reducing its cardiotoxicity; however, it remains unclear whether liposomal doxorubicin is therapeutically superior to free doxorubicin. Here, we demonstrate a novel PEGylated liposome system, named DAFODIL (Doxorubicin And 5-Flurouracil Optimally Delivered In a Liposome) that inarguably offers superior therapeutic efficacies compared to free drug administrations. Delivery of synergistic ratios of this drug pair led to greater than 90% reduction in tumor growth of murine 4T1 mammary carcinoma in vivo. By exploiting synergistic ratios, the effect was achieved at remarkably low doses, far below the maximum tolerable drug doses. Our approach re-invents the use of liposomes for multi-drug delivery by providing a chemotherapy vehicle which can both reduce toxicity and improve therapeutic efficacy. This methodology is made feasible by the extension of the ammonium-sulfate gradient encapsulation method to nucleobase analogues, a liposomal entrapment method once conceived useful only for anthracyclines. Therefore, our strategy can be utilized to efficiently evaluate various chemotherapy combinations in an effort to translate more effective combinations into the clinic. PMID:27034194

  15. Metformin decreases the dose of chemotherapy for prolonging tumor remission in mouse xenografts involving multiple cancer cell types

    PubMed Central

    Iliopoulos, Dimitrios; Hirsch, Heather A.; Struhl, Kevin

    2011-01-01

    Metformin, the first-line drug for treating diabetes, selectively kills the chemotherapy-resistant, sub-population of cancer stem cells in genetically distinct types of breast cancer cell lines. In mouse xenografts, injection of metformin and the chemotherapeutic drug doxorubicin near the tumor is more effective than either drug alone in blocking tumor growth and preventing relapse. Here, we show that metformin is equally effective when given orally together with paclitaxel, carboplatin, and doxorubicin indicating that metformin works together with a variety of standard chemotherapeutic agents. In addition, metformin has comparable effects on tumor regression and preventing relapse when metformin combined with a 4-fold reduced dose of doxorubicin that is not effective as a monotherapy. Lastly, the combination of metformin and doxorubicin prevents relapse in xenografts generated with prostate and lung cancer cell lines. These observations provide further evidence for the cancer stem cell hypothesis for cancer relapse, as well as an experimental rationale for using metformin as part of combinatorial therapy in a variety of clinical settings and for reducing the chemotherapy dose in cancer patients. PMID:21415163

  16. Safety and efficacy of pegfilgrastim compared to granulocyte colony stimulating factor (G-CSF) supporting a dose-intensive, rapidly cycling anti-metabolite containing chemotherapy regimen (Hyper-CVAD) for lymphoid malignancy.

    PubMed

    Lane, Steven W; Crawford, Julie; Kenealy, Melita; Cull, Gavin; Seymour, John F; Prince, H Miles; Marlton, Paula; Gill, Devinder; Mollee, Peter N

    2006-09-01

    Pegfilgrastim (Neulasta) has proven efficacy as supportive therapy in a variety of 21-day chemotherapy regimens, but has not been studied in dose intensive, rapidly cycling regimens utilising cell-cycle active drugs (e.g. anti-metabolites) such as hyper-CVAD. This study examined whether pegfilgrastim was safe and lead to similar kinetics of neutrophil recovery as daily granulocyte colony stimulating factor (G-CSF). Using retrospective analysis, patients receiving pegfilgrastim (6 mg) were matched with controls (G-CSF 5 microg kg-1 per day) for a cycle of chemotherapy, prior chemotherapy, dose of cytarabine received, age (<60 or >60 years), diagnosis and bone marrow involvement. The primary endpoint was duration of grade IV neutropenia (absolute neutrophil count, ANC < 500 microl-1). Secondary endpoints included time to neutrophil recovery, incidence of febrile neutropenia, positive blood cultures and delay in subsequent chemotherapy. This study identified 124 pegfilgrastim supported cycles in 43 patients and successfully matched them to 124 G-CSF supported cycles from 38 patients treated between January 1999 and July 2005. There were no significant differences between pegfilgrastim and G-CSF groups in baseline or treatment-related variables. The median duration of grade IV neutropenia was 4 days in both groups (P = 0.55). Time to neutrophil recovery, incidence of febrile neutropenia, positive blood cultures and delay in subsequent chemotherapy were similar in both groups. Once per cycle dosing of pegfilgrastim appears safe and as effective as daily G-CSF for supporting the hyper-CVAD chemotherapy regimen. PMID:17064993

  17. Full dose paclitaxel plus vinorelbine as salvage chemotherapy in anthracycline-resistant advanced breast cancer: a phase II study.

    PubMed

    Polyzos, A; Tsavaris, N; Kosmas, C; Gogas, H; Toufexi, H; Kosmidis, C; Markopoulos, C; Giannopoulos, A; Papadopoulos, O; Stamatiadis, D; Kouraklis, G

    2003-12-01

    This phase II trial studied the efficacy and toxicity of full dose paclitaxel plus vinorelbine, as salvage chemotherapy in patients with metastatic breast cancer resistant to anthracyclines. Patients received vinorelbine (30 mg/m2) followed 1 hour later by full dose paclitaxel (175 mg/m2) every 3 weeks for a maximum of 8 cycles or until disease progression. Because of the heavy pretreatment of the patients, prophylactic granulocyte-colony stimulating factor (5 microg/kg) was administered daily for 5-10 days. To minimize potentially cumulative neurotoxicity due to both agents, amifostine was given prior to chemotherapy. Thirty-four patients: 8 with tumors primary resistant and 26 with tumors recurring within 3-6 months after anthracycline treatment, were evaluable for efficacy and toxicity. Objective responses occurred in 11 patients [32%; 95% confidence interval (CI): 16.3-47.7%), all partial responses. Responses were observed in lung and liver. The median response duration was 4 months (range 3-7), median time to progression was 5 months (range 3-9) and median overall survival was 8 months (range 4-24). Neutropenia was dose limiting (35% grade 3-4 toxicity). The left ventricular ejection fraction, measured and followed in 18 patients, fell less than 20% below baseline level in 9 patients (50%), but only one patient developed congestive cardiac failure. The paclitaxel-vinorelbine regimen was moderately tolerated and moderately effective in poor prognosis breast cancer patients with visceral metastases and tumors resistant to anthracyclines. The combination at these doses and schedules should be considered in the design of regimens for advanced breast cancer. PMID:14998089

  18. Predictive value of early 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) during salvage chemotherapy in relapsing/refractory Hodgkin lymphoma (HL) treated with high-dose chemotherapy.

    PubMed

    Castagna, Luca; Bramanti, Stefania; Balzarotti, Monica; Sarina, Barbara; Todisco, Elisabetta; Anastasia, Antonella; Magagnoli, Massimo; Mazza, Rita; Nozza, Andrea; Giordano, Laura; Rodari, Marcello; Rinifilo, Eva; Chiti, Arturo; Santoro, Armando

    2009-05-01

    This retrospective study evaluated whether early 2-[fluorine-18]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) after two cycles of salvage chemotherapy (PET2) could predict survival after high-dose chemotherapy (HDC). Twenty-four Hodgkin lymphoma (HL) patients were included. PET2 was negative in 58% and positive in 42% of patients. Ninety per cent of patients (9/10) with positive PET2 relapsed after HDC while all but one patient with negative PET2 maintained a complete remission. The 2-year progression-free survival was 93% vs. 10% for patients with negative and positive PET2, respectively (P < 0.001). This study shows that interim PET can predict the outcome after high-dose chemotherapy in HL patients. PMID:19344403

  19. Antiangiogenic agents significantly improve survival in tumor-bearing mice by increasing tolerance to chemotherapy-induced toxicity

    PubMed Central

    Zhang, Danfang; Hedlund, Eva-Maria E.; Lim, Sharon; Chen, Fang; Zhang, Yin; Sun, Baocun; Cao, Yihai

    2011-01-01

    Chemotherapy-induced broad toxicities are the leading cause of the drug-induced mortality in cancer patients. Antiangiogenic drugs (ADs) in combination with chemotherapy are widely used as front-line therapy for the treatment of various human cancers. However, the beneficial mechanisms underlying combination therapy are poorly understood. Here we show that, in several murine tumor models, administration of sunitinib markedly reduced chemotherapy-induced bone marrow toxicity. Intriguingly, in a sequential treatment regimen, delivery of ADs followed by chemotherapy demonstrated superior survival benefits compared with simultaneous administration of two drugs. In murine tumor models, we show that VEGF increased chemotoxicity by synergistically suppressing bone marrow hematopoiesis with cytostatic drugs. These findings shed light on molecular mechanisms by which ADs in combination with chemotherapy produce survival benefits in cancer patients and provide conceptual information guiding future designs of clinical trials, current practice, and optimization of ADs for the treatment of cancer. PMID:21367692

  20. Intensity-Modulated Radiotherapy Might Increase Pneumonitis Risk Relative to Three-Dimensional Conformal Radiotherapy in Patients Receiving Combined Chemotherapy and Radiotherapy: A Modeling Study of Dose Dumping

    SciTech Connect

    Vogelius, Ivan S.; Westerly, David C.; Cannon, George M.; Mackie, Thomas R.; Mehta, Minesh P.; Sugie, Chikao; Bentzen, Soren M.

    2011-07-01

    Purpose: To model the possible interaction between cytotoxic chemotherapy and the radiation dose distribution with respect to the risk of radiation pneumonitis. Methods and Materials: A total of 18 non-small-cell lung cancer patients previously treated with helical tomotherapy at the University of Wisconsin were selected for the present modeling study. Three treatment plans were considered: the delivered tomotherapy plans; a three-dimensional conformal radiotherapy (3D-CRT) plan; and a fixed-field intensity-modulated radiotherapy (IMRT) plan. The IMRT and 3D-CRT plans were generated specifically for the present study. The plans were optimized without adjusting for the chemotherapy effect. The effect of chemotherapy was modeled as an independent cell killing process by considering a uniform chemotherapy equivalent radiation dose added to all voxels of the organ at risk. The risk of radiation pneumonitis was estimated for all plans using the Lyman and the critical volume models. Results: For radiotherapy alone, the critical volume model predicts that the two IMRT plans are associated with a lower risk of radiation pneumonitis than the 3D-CRT plan. However, when the chemotherapy equivalent radiation dose exceeds a certain threshold, the radiation pneumonitis risk after IMRT is greater than after 3D-CRT. This threshold dose is in the range estimated from clinical chemoradiotherapy data sets. Conclusions: Cytotoxic chemotherapy might affect the relative merit of competing radiotherapy plans. More work is needed to improve our understanding of the interaction between chemotherapy and the radiation dose distribution in clinical settings.

  1. Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapy: results of a randomized, double-blind phase III trial†

    PubMed Central

    Weinstein, C.; Jordan, K.; Green, S. A.; Camacho, E.; Khanani, S.; Beckford-Brathwaite, E.; Vallejos, W.; Liang, L. W.; Noga, S. J.; Rapoport, B. L.

    2016-01-01

    Background To establish the role of antiemetic therapy with neurokinin-1 (NK1) receptor antagonists (RAs) in nonanthracycline and cyclophosphamide (AC)-based moderately emetogenic chemotherapy (MEC) regimens, this study evaluated single-dose intravenous (i.v.) fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting (CINV) associated with non-AC MEC. Patients and methods In this international, phase III, double-blind trial, adult cancer subjects scheduled to receive ≥1 non-AC MEC on day 1 were randomized to a regimen comprising single-dose i.v. fosaprepitant 150 mg or placebo along with ondansetron and dexamethasone on day 1; control regimen recipients received ondansetron on days 2 and 3. Primary end points were the proportion of subjects achieving a complete response (CR; no vomiting and no use of rescue medication) in the delayed phase (25–120 h after MEC initiation) and safety. Secondary end points included CR in the overall and acute phases (0–120 and 0–24 h after MEC initiation, respectively) and no vomiting in the overall phase. Nausea and the Functional Living Index-Emesis were assessed as exploratory end points. Results The fosaprepitant regimen improved CR significantly in the delayed (78.9% versus 68.5%; P < 0.001) and overall (77.1% versus 66.9%; P < 0.001) phases, but not in the acute phase (93.2% versus 91.0%; P = 0.184), versus control. In the overall phase, the proportion of subjects with no vomiting (82.7% versus 72.9%; P < 0.001) and no significant nausea (83.2% versus 77.9%; P = 0.030) was also significantly improved with the fosaprepitant regimen. The fosaprepitant regimen was generally well tolerated. Conclusion Single-dose fosaprepitant added to a 5-HT3 RA and dexamethasone was well tolerated and demonstrated superior control of CINV (primary end point achieved) associated with non-AC MEC. This is the first study to evaluate NK1 RA therapy as an i.v. formulation in a well-defined non-AC MEC population. Clinical

  2. Is there a role for high dose chemotherapy and blood stem cell rescue in childhood hepatoblastoma presenting with lung metastases? A case report and literature review.

    PubMed

    Provenzi, Massimo; Saettini, Francesco; Conter, Valentino; Giraldi, Eugenia; Foglia, Carlo; Cavalleri, Laura; Colledan, Michele; D'Antiga, Lorenzo; Perilongo, Giorgio; Da Dalt, Liviana

    2013-01-01

    We report the use of high dose chemotherapy with peripheral blood stem cell rescue as a consolidation treatment for a 3-year-old child affected by metastatic hepatoblastoma, who achieved complete lung response only after conventional treatment. The patient is presently alive 27 months after high dose chemotherapy with blood stem cell rescue with no evidence of disease.The role of high dose chemotherapy with blood stem cell rescue to consolidate the complete clearing of lung disease in metastatic hepatoblastoma remains controversial; the data available in the literature and our experience seems to suggest to keep this treatment option open to further consideration in the clinical setting of high-risk patients. PMID:24148885

  3. A multicenter, randomized trial of flat dosing versus intrapatient dose escalation of single-agent carboplatin as first-line chemotherapy for advanced ovarian cancer: an SGCTG (SCOTROC 4) and ANZGOG study on behalf of GCIG

    PubMed Central

    Banerjee, S.; Rustin, G.; Paul, J.; Williams, C.; Pledge, S.; Gabra, H.; Skailes, G.; Lamont, A.; Hindley, A.; Goss, G.; Gilby, E.; Hogg, M.; Harper, P.; Kipps, E.; Lewsley, L-A; Hall, M.; Vasey, P.; Kaye, S. B.

    2015-01-01

    Background The aim of the study is to demonstrate that intrapatient dose escalation of carboplatin would improve the outcome in ovarian cancer compared with flat dosing. Patients and methods Patients with untreated stage IC-IV ovarian cancer received six cycles of carboplatin area under the curve 6 (AUC 6) 3 weekly either with no dose modification except for toxicity (Arm A) or with dose escalations in cycles 2–6 based on nadir neutrophil and platelet counts (Arm B). The primary end-point was progression-free survival (PFS). Results Nine hundred and sixty-four patients were recruited from 71 centers. Dose escalation was achieved in 77% of patients who had ≥1 cycle. The median AUCs (cycle 2–6) received were 6.0 (Arm A) and 7.2 (Arm B) (P < 0.001). Grade 3/4 non-hematological toxicity was higher in Arm B (31% versus 22% P = 0.001). The median PFS was 12.1 months in Arm A and B [hazard ratio (HR) 0.99; 95% confidence interval (CI) 0.85–1.15; P = 0.93]. The median overall survival (OS) was 34.1 and 30.7 months in Arms A and B, respectively (HR 0.98; 95% CI 0.81–1.18, P = 0.82). In multivariate analysis, baseline neutrophil (P < 0.001), baseline platelet counts (P < 0.001) and the difference between white blood cell (WBC) and neutrophil count (P = 0.009) had a significant adverse prognostic value. Conclusions Intrapatient dose escalation of carboplatin based on nadir blood counts is feasible and safe. However, it provided no improvement in PFS or OS compared with flat dosing. Baseline neutrophils over-ride nadir counts in prognostic significance. These data may have wider implications particularly in respect of the management of chemotherapy-induced neutropenia. PMID:23041585

  4. Multi-Institution Prospective Trial of Reduced-Dose Craniospinal Irradiation (23.4 Gy) Followed by Conformal Posterior Fossa (36 Gy) and Primary Site Irradiation (55.8 Gy) and Dose-Intensive Chemotherapy for Average-Risk Medulloblastoma

    SciTech Connect

    Merchant, Thomas E. Kun, Larry E.; Krasin, Matthew J.; Wallace, Dana; Chintagumpala, Murali M.; Woo, Shiao Y.; Ashley, David M.; Sexton, Maree; Kellie, Stewart J.; Ahern, Verity M.B.B.S.; Gajjar, Amar

    2008-03-01

    Purpose: Limiting the neurocognitive sequelae of radiotherapy (RT) has been an objective in the treatment of medulloblastoma. Conformal RT to less than the entire posterior fossa (PF) after craniospinal irradiation might reduce neurocognitive sequelae and requires evaluation. Methods and Materials: Between October 1996 and August 2003, 86 patients, 3-21 years of age, with newly diagnosed, average-risk medulloblastoma were treated in a prospective, institutional review board-approved, multi-institution trial of risk-adapted RT and dose-intensive chemotherapy. RT began within 28 days of definitive surgery and consisted of craniospinal irradiation (23.4 Gy), conformal PF RT (36.0 Gy), and primary site RT (55.8 Gy). The planning target volume for the primary site included the postoperative tumor bed surrounded by an anatomically confined margin of 2 cm that was then expanded with a geometric margin of 0.3-0.5 cm. Chemotherapy was initiated 6 weeks after RT and included four cycles of high-dose cyclophosphamide, cisplatin, and vincristine. Results: At a median follow-up of 61.2 months (range, 5.2-115.0 months), the estimated 5-year event-free survival and cumulative incidence of PF failure rate was 83.0% {+-} 5.3% and 4.9% {+-} 2.4% ({+-} standard error), respectively. The targeting guidelines used in this study resulted in a mean reduction of 13% in the volume of the PF receiving doses >55 Gy compared with conventionally planned RT. The reductions in the dose to the temporal lobes, cochleae, and hypothalamus were statistically significant. Conclusion: This prospective trial has demonstrated that irradiation of less than the entire PF after 23.4 Gy craniospinal irradiation for average-risk medulloblastoma results in disease control comparable to that after treatment of the entire PF.

  5. Clinical results of high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation in children with advanced stage rhabdomyosarcoma.

    PubMed

    Kim, Nam Kyun; Kim, Hyo Sun; Suh, Chang-Ok; Kim, Hyun Ok; Lyu, Chuhl Joo

    2012-09-01

    Regardless of improvement in cure of Rhabdomyosarcoma (RMS), the results in treatment of advanced stage of RMS in children are still dismal. Recently, high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (HDC/APBSCT) has been tried to manage the advanced high-risk RMS patients. We investigated the effectiveness of HDC/APBSCT by reviewing the clinical records of high-risk pediatric RMS patients in single institute database. Over twenty years, 37 patients were diagnosed as RMS with high-risk at the time of first diagnosis. These patients were classified as two groups according to treatment method. The first group was HDC/APBSCT and the other was conventional multi-agent chemotherapy group. Differences of clinical results between the two groups were analyzed. The median age of patients was 5 yr, ranging from 6 months to 15 yr. The 5-yr event free survival rate (EFS) of all patients was 24.8% ± 4.8%. HDC/APBSCT group and conventional multi-agent chemotherapy group were 41.3% ± 17.8% and 16.7% ± 7.6% for 5-yr EFS, respectively (P = 0.023). There was a significant difference in the result of HDC/APBSCT between complete remission or very good partial response group and poor response group (50% ± 20.4% vs 37.5% ± 28.6%, P = 0.018). HDC/APBSCT can be a promising treatment modality in high-risk RMS patients. PMID:22969254

  6. Repeated high-dose chemotherapy followed by purged autologous bone marrow transplantation as consolidation therapy in metastatic neuroblastoma.

    PubMed

    Hartmann, O; Benhamou, E; Beaujean, F; Kalifa, C; Lejars, O; Patte, C; Behard, C; Flamant, F; Thyss, A; Deville, A

    1987-08-01

    Among 62 children over 1 year of age at diagnosis, who were treated for stage IV neuroblastoma, 33 entered complete remission (CR) or good partial remission (GPR) after conventional therapy and received high-dose chemotherapy (HDC) with in vitro purged autologous bone marrow transplantation (ABMT) as consolidation therapy. The HDC was a combination of carmustine (BCNU), teniposide (VM-26), and melphalan. Thirty-three patients received one course of this regimen, and 18 received two courses. At present, 16 of the 33 grafted patients are alive in continuous CR, with a median follow-up of 28 months. Toxicity of this regimen was tolerable, principally marked by bone marrow depression and gastrointestinal (GI) tract complications. Four complication-related deaths were observed. Relapse post-ABMT occurred most often in the bone marrow. Under this treatment, actuarial disease-free survival is improved compared with that observed under conventional therapy. PMID:3305792

  7. Treatment of primary mediastinal large B cell lymphoma with an alternating chemotherapy regimen based on high-dose methotrexate.

    PubMed

    Fietz, T; Knauf, W U; Hänel, M; Franke, A; Freund, M; Thiel, E

    2009-05-01

    Primary mediastinal large B cell lymphomas (MLCL) differ from other diffuse large cell lymphomas, leading to a description as a separate entity in the current World Health Organization classification. Dose intensification improves long-term results, but no standard therapy has been established so far. We investigated the use of a high-dose methotrexate-based alternating chemotherapy regimen (B-ALL protocol of the German ALL study group) followed by consolidative mediastinal radiotherapy first as a single-center trial, then later as a prospective multicenter trial in 44 patients with a median age of 33 years. Response rates exceeded 90% with an overall survival rate of 80% in the single-center group (8.6 years median follow-up) and 82% in the multicenter group (2.5 years follow-up).Short-term toxicity was manageable, but required hospitalization: the rates of grade 3 or 4 toxicity were 20% (for mucositis), 42% (for neutropenia), 29% (for thrombocytopenia), and 9% (for neutropenic fever). No relapse occurred more than 2 years after diagnosis and initiation of treatment, but unfortunately, no patient with overt progression or relapse within these 2 years could be salvaged. Future directions in the treatment of MLCL will not focus on further dose intensification, but rather on the incorporation of (radio)immunotherapy as a therapeutic tool and gene expression profiling as well as positron emission tomography-computed tomography as stratifying tools. PMID:18853160

  8. HIGH-DOSE CHEMOTHERAPY WITH BLOOD OR BONE MARROW TRANSPLANTS FOR RHABDOMYOSARCOMA

    PubMed Central

    Stiff, Patrick J.; Agovi, Manza-A.; Antman, Karen H.; Blaise, Didier; Camitta, Bruce M.; Cairo, Mitchell S.; Childs, Richard W.; Edwards, John R; Gale, Robert Peter; Hale, Gregory A.; Lazarus, Hillard M.; Arora, Mukta

    2009-01-01

    Rhabdomyosarcoma (RMS), the most common soft-tissue sarcoma in children, is cured with conventional therapy in 70%. However, 5 year survival for those who relapse is about 30% and drops to about 15% for those with unfavorable histologies (alveolar/undifferentiated subtypes). We describe outcomes of 62 subjects receiving autologous blood/bone marrow transplants for RMS between 1989 and 2003 and reported to CIBMTR. Histological subtype was confirmed by reviewing pathology reports. Transplant-related mortality (TRM), progression-free survival (PFS) and survival were evaluated. Overall 73% of subjects were < 20 years; 39% had cancer bulk >5cm, 63% had metastasis at diagnosis, 55% had unfavorable histologies, 92% had cancer responsive to chemotherapy pretransplant and 67% were in 1st remission. The 1-year TRM was 5% (95% CI, 1–12%) and the 5 year PFS and survival were 29% (95% CI, 18–41%) and 32% (95% CI, 21–44%) respectively. There was only a 4% relapse rate after the first year. There were no differences in 5 year PFS or survival based on histological subtype, transplant in 1st remission vs. relapse (36% vs. 29%; p=0.5), or transplantation for poor-risk histologies in 1st remission vs. relapse (34% vs. 33%; p=0.9). Our data indicate that autotransplants for RMS disease are typically done in patients with disease responsive to chemotherapy pretransplant, with approximately one-third long-term survivors. Despite high risk factors, we also found a low TRM, perhaps reflecting the migration from marrow to blood stem cells as the graft source. Even when performed after relapse for alveolar/undifferentiated histologies, long-term survivals were seen seemingly better than results with conventional therapies. PMID:19961947

  9. Low-dose decitabine plus all-trans retinoic acid in patients with myeloid neoplasms ineligible for intensive chemotherapy.

    PubMed

    Wu, Wei; Lin, Yan; Xiang, Lili; Dong, Weimin; Hua, Xiaoying; Ling, Yun; Li, Haiqian; Yan, Feng; Xie, Xiaobao; Gu, Weiying

    2016-06-01

    In our previous in vitro trials, decitabine and all-trans retinoic acid (ATRA) demonstrated synergistic effects on growth inhibition, differentiation, and apoptosis in SHI-1 cells; in K562 cells, ATRA enhanced the effect of decitabine on p16 demethylation, and the combination of the two drugs was found to activate RAR-β expression (p16 and RAR-β are two tumor suppressor genes). On the rationale of our in vitro trials, we used low-dose decitabine and ATRA to treat 31 myeloid neoplasms deemed ineligible for intensive chemotherapy. The regimen consisted of decitabine at the dose of 15 mg/m(2) intravenously over 1 h daily for consecutive 5 days and ATRA at the dose of 20 mg/m(2) orally from day 1 to 28 except day 4 to 28 in the first cycle, and the regimen was repeated every 28 days. After 6 cycles, decitabine treatment was stopped, and ATRA treatment was continued for maintenance treatment. Treated with a median of 2 cycles (range 1-6), 7 patients (22.6 %) achieved complete remission (CR), 7 (22.6 %) marrow CR (mCR), and 4 (12.9 %) partial remission (PR). The overall remission (CR, mCR, and PR) rate was 58.1 %, and the best response (CR and mCR) rate was 45.2 %. The median overall survival (OS) was 11.0 months, the 1-year OS rate was 41.9 %, and the 2-year OS rate was 26.6 %. In univariate analyses, age, performance status, comorbidities, white blood cell counts and platelets at diagnosis, percentage of bone marrow blasts, karyotype, and treatment efficacy demonstrated no impacts on OS (P > 0.05, each). Main side effects were tolerable hematologic toxicities. In conclusion, low-dose decitabine plus ATRA is a promising treatment for patients with myeloid neoplasms judged ineligible for intensive chemotherapy. PMID:27116384

  10. Dose-adjusted Chemotherapy for Untreated c-MYC-positive Lymphoma

    Cancer.gov

    In this trial, adult patients with newly diagnosed Burkitt lymphoma or c-MYC-positive DLBCL will be separated into low-risk and high-risk groups; those in the low-risk group will be treated with at least three cycles of dose-adjusted EPOCH-R

  11. A randomised trial of low-dose/high-frequency chemotherapy as palliative treatment of poor-prognosis small-cell lung cancer: a Cancer research Campaign trial.

    PubMed Central

    James, L. E.; Gower, N. H.; Rudd, R. M.; Spiro, S. G.; Harper, P. G.; Trask, C. W.; Partridge, M.; Ruiz de Elvira, M. C.; Souhami, R. L.

    1996-01-01

    We report the results of a randomised trial in extensive small-cell lung cancer (SCLC) of a novel approach to palliative chemotherapy. A widely used 3 weekly regimen was compared with the same drugs given at half the dose but twice the frequency with the same intended overall dose intensity (DI). A total of 167 patients defined as having extensive SCLC with adverse prognostic features were randomised to receive either a 3 weekly regimen of cisplatin 60 mg m-2 i.v. on day 1 and etoposide 120 mg m-2 i.v. on day 1 and 100 mg b.d. orally on days 2 and 3 alternating with cyclophosphamide 600 mg m-2 i.v., doxorubicin 50 mg m-2 i.v. and vincristine 2 mg i.v. all on day 1 for a maximum of six courses (3 weekly); or treatment with the same drugs but with each course consisting of half the 3 weekly dose given every 10 or 11 days for a maximum of 12 courses. In the 10/11 day regimen overall response rate was 58.9% (95% CI, 47.9-69.2%) with 12.8% complete responses (CR). For the 3 weekly treatment the overall response rate was 44.9% (95% CI, 35.0-55.5%) with 10.1% CR. Median survival was similar in the two arms at 6.4 months (95% CI, 4.9-7.3 months) and 5.8 months (95% CI, 4.0-6.6 months) respectively. Survival at 1 year was 9.9% (95% CI, 5.0-18.5%) and 8.9% (95% CI, 4.6-16.6%). The 95% CI for the difference in survival at 1 year is -7.09% to +9.09%. Haematological toxicity and treatment delays owing to infection were more frequent with the 10/11 day regimen but other toxicities were equal in both arms. Other aspects of quality of life were measured in a small representative cohort of patients using a daily diary card (DDC). There was a trend of improved quality of life on the 10/11 day arm, but there was little difference between the two treatments. The trial shows that a low-dose/high-frequency regimen with the same DI as conventionally scheduled chemotherapy gives similar response rates and survival. This and other modifications of the schedule may offer new approaches to

  12. High-dose chemotherapy supported by autologous stem cell transplantation in patients with primary central nervous system lymphoma: facts and opinions.

    PubMed

    Ferreri, Andrés J M; Crocchiolo, Roberto; Assanelli, Andrea; Govi, Silvia; Reni, Michele

    2008-11-01

    The standard approach to primary central nervous system lymphomas (PCNSL), that is high-dose methotrexate (HD-MTX)-based chemotherapy followed by whole-brain irradiation (WBRT), is associated with disappointing outcome. Moreover, this strategy is heavily conditioned by increased risk of disabling neurotoxicity, mostly among elderly patients. Several drugs and strategies have been investigated to improve results and neurotolerability. Among others, some investigators focused on the use of high-dose chemotherapy supported by autologous stem cells transplant (HDC/ASCT) as consolidation after primary chemotherapy. This approach has been used as salvage therapy in patients who experienced progressive disease or relapse after conventional chemo-radiotherapy or as consolidation after primary HD-MTX-based chemotherapy, replacing or preceding WBRT. Evidence supporting the role of HDC/ASCT is growing but several questions are still unanswered. The best conditioning regimen, the role of concomitant intrathecal chemotherapy, the neurotoxicity risk of further WBRT after transplant, the best time for response assessment and late effects both on neurological performance and extraneural organs remain to be characterised. This critical review is focused on the analysis of published experiences on HDC/ASCT in PCNSL in order to provide preliminary answers to the most pressing questions in this field. PMID:19021047

  13. Acute and late toxicity following adjuvant high-dose chemotherapy for high-risk primary operable breast cancer--a quality assessment study.

    PubMed

    Svane, Inge M; Homburg, Keld M; Kamby, Claus; Nielsen, Dorte L; Roer, Ole; Sliffsgaard, Dorte; Johnsen, Hans E; Hansen, Steen W

    2002-01-01

    From 1996 to 2000, high-dose chemotherapy with haematopoietic stem-cell support was used as an adjuvant treatment strategy for management of primary high-risk breast cancer patients with more than five positive nodes. This single institution study included 52 women aged < or = 56 years with primary operable breast cancer and > or = 6 tumour-positive axillary lymph nodes. The treatment regimen consisted of at least three initial courses of FEC (5-fluorouracil, epirubicin, cyclophosphamide) followed by high-dose chemotherapy (cyclophosphamide, thiotepa, carboplatin) supported by autologous peripheral blood stem-cell reinfusion. This study focuses on quality control including evaluation of toxicity, supportive therapy and assessment of the stem-cell products. Cytokeratin 19 positive cells were found in the stem-cell product from 3/37 patients. Data regarding organ toxicity were used for evaluation of short- and long-term side effects. Substantial acute toxicity and frequent catheter-related infections were found. Long-term toxicities included reduced lung diffusion capacity (n = 36), fatigue (n = 14), arthralgia/myalgia (n = 10), neurotoxicity (n = 9) and memory loss (n = 4). However, most toxicities were grade 1-2 and reversible within two years. No treatment-related death occurred. Within a median follow-up of 30 months (range, 11-57), 25% of the patients had relapsed. Recurrence-free survival was 75% and overall survival was 88% three years after the start of treatment. Overall, high-dose chemotherapy was relatively well tolerated, with manageable toxicity and an acceptable requirement of supportive therapy. Until now, high-dose chemotherapy has not proven superior to conventional-dose adjuvant chemotherapy, therefore it is necessary in the future to focus on well-designed randomized studies. PMID:14651213

  14. Health-related quality of life in outpatients with primary central nervous system lymphoma after radiotherapy and high-dose methotrexate chemotherapy

    PubMed Central

    Okita, Yoshiko; Narita, Yoshitaka; Miyakita, Yasuji; Miyahara, Ruriko; Ohno, Makoto; Takahashi, Masamichi; Nonaka, Masahiro; Kanemura, Yonehiro; Nakajima, Shin; Fujinaka, Toshiyuki

    2016-01-01

    Chemoradiotherapy for primary central nervous system lymphoma (PCNSL) is associated with a considerable risk of long-term neurotoxicity. The present study aimed to assess the health-related quality of life (HRQOL) of outpatients with PCNSL who have received radiotherapy and high-dose methotrexate (HDMTX) chemotherapy, and to determine the factors that cause a decline in HRQOL and interfere with home living. A total of 37 patients were surveyed 0.9–14.2 years after their initial diagnosis and treatment. Each patient completed a multi-part HRQOL questionnaire that was used to examine the associations of HRQOL scores with leukoencephalopathy, Karnofsky performance status (KPS) scores, age, history of recurrence and HDMTX-based chemoradiotherapy. The results demonstrated that the history of recurrence, number of cycles of MTX chemotherapy and age affected the development of leukoencephalopathy. Reductions in KPS score were associated with a history of recurrence (P=0.03), but not with leukoencephalopathy (P=0.8). KPS score, leukoencephalopathy and age were significantly associated with a decline in HRQOL score. A decline in the HRQOL associated with a reduction in KPS score was also observed by multivariate analyses. Deterioration of the HRQOL among outpatients with PCNSL post-chemoradiotherapy was significantly associated with older age (≥66 years) and decreased KPS score. Older patients with a history of recurrence had a higher risk for deteriorated QOL due to development of leukoencephalopathy. Therefore, it is recommended that clinicians monitor the KPS score among outpatients with PCNSL. QOL examination for older patients with a lower KPS score was found to be particularly important for identifying any obstacles for home living. PMID:27602217

  15. Relationship of gonadal activity and chemotherapy-induced gonadal damage

    SciTech Connect

    Rivkees, S.A.; Crawford, J.D.

    1988-04-08

    The authors tested the hypothesis that chemotherapy-induced gonadal damage is proportional to the degree of gonadal activity during treatment. Thirty studies that evaluated gonadal function after cyclophosphamide therapy for renal disease or combination chemotherapy for Hodgkin's disease or acute lymphocytic leukemia provided data for analysis. Data were stratified according to sex, illness, chemotherapeutic regimen and dose, and pubertal stage at the time of treatment. Chemotherapy-induced damage was more likely to occur in patients who were treated when sexually mature compared with those who were treated when prepubertal. Males were significantly more frequently affected than females when treated for renal disease of Hodgkin's disease. Chemotherapy-induced damage was also more likely to occur when patients were treated with large doses of alkylating agents. These data suggest that chemotherapy-induced damage is proportional to gonadal activity. Further efforts are needed to test whether induced gonadal quiescence during chemotherapy will reduce the strikingly high incidence of gonadal failure following chemotherapy.

  16. Nutritional status is superior to the ECOG performance status in predicting the dose-intensity of the GEMOX chemotherapy regimen in patients with advanced cancer.

    PubMed

    Cessot, Anatole; Coriat, Romain; Mir, Oliver; Boudou-Rouquette, Pascaline; Giroux, Julie; Durand, Jean-Philippe; Alexandre, Jérôme; Goldwasser, Francois

    2013-01-01

    The increasing number of unfit patients calls for better risk assessment prior to initiating anti-tumor treatment. This is a major concern in the prevention and reduction of treatment-related complications. The aim of our study was to evaluate the nutritional status for the risk assessment of patients qualifying to receive the gemcitabine and oxaliplatin (GEMOX) regimen. This single-center, retrospective study examined baseline clinical and biological characteristics in a cohort of 165 unselected, consecutive cancer patients receiving GEMOX. Malnutrition was defined as either body mass index (BMI) <18.5 kg/m(2), body weight loss >10% over 3 mo, or albuminemia <35 g/L. A total of 165 patients (median age 61 yr, PS 0-1: 71%) were studied. Malnutrition was seen in 43% of PS 0-1 patients, vs. 60% of PS 2 and 66% of PS 3 patients (P > 0.05). Median relative dose-intensity was 0.90 (0.17-1.04). GEMOX dose-intensity correlated negatively with loss of baseline weight (r = -0.24, P < 0.02). In patients who did not complete more than 2 cycles of chemotherapy, median PS (P < 0.01), mean C-reactive protein (CRP; P < 0.01), and mean albuminemia (P < 0.05) were, respectively, significantly higher, higher, and lower. Malnutrition is associated with a high risk of early discontinuance of treatment. Systematic basal evaluation of the nutritional status, including albuminemia and BMI, is recommended. PMID:24099412

  17. Evaluation of the effect of age on treatment-related mortality and relapse in patients with high-risk primary breast cancer receiving high-dose chemotherapy.

    PubMed

    Nieto, Yago; Shpall, Elizabeth J; Bearman, Scott I; Jones, Roy B

    2005-06-01

    There are contradictory results regarding a potential increased responsiveness of younger women with high-risk primary breast cancer to high-dose compared with standard-dose chemotherapy. Observations from some, but not all, randomized trials, suggest that the potential benefit of high-dose treatment may be limited to younger patients. We analyzed, at median follow-up of 8 years, the prognostic effect of age in 264 patients enrolled in prospective phase II and III trials of high-dose chemotherapy, using a uniform regimen. Median age was 49 (range, 36-71). Among patients < or = 49 and > 49 years of age, the relapse rates were 27% and 25%, respectively (P = 0.7). In those age groups, the transplant-related mortality rates were 6.5% and 4%, respectively (P = 0.8). No age differences were observed between patients surviving transplant (median age 49) and those who experienced transplant-related mortality (median 47.5) (P = 0.9). Event-free survival (P = 0.3) and overall survival (P = 0.4) did not differ between patients < or = 49 and > 49 years of age. In conclusion, we did not detect a detrimental effect of older age on transplant-related mortality or relapse after high-dose chemotherapy for high-risk primary breast cancer at long-term follow-up. The debate about the age effect in this population remains unsettled. PMID:15923796

  18. Effect of folate status and methylenetetrahydrofolate reductase genotypes on the complications and outcome of high dose methotrexate chemotherapy in north Indian children with acute lymphoblastic leukemia

    PubMed Central

    Moulik, Nirmalya Roy; Kumar, Archana; Agrawal, Suraksha; Mahdi, Abbas Ali; Kumar, Ashutosh

    2016-01-01

    Purpose: The genes of the folate metabolic pathway have been associated with toxicities during high dose methotrexate therapy for childhood ALL, however, the importance of intrinsic folate status in this regard is unclear. Methods: In the present study the effect of precourse folate levels and MTHFR genotypes on the complications during high dose methotrexate chemotherapy in children with ALL were examined. Results: Twenty-one children were studied. Folate deficiency was associated with higher incidence of neutropenia (P = 0.03) and longer duration of chemotherapy interruption (P = 0.009). Children with MTHFR1298 mutations needed more red cell transfusion (P = 0.03). All 3 deaths encountered were seen in folate deficient children. Conclusions: Folate deficiency was associated with higher complications during high dose methotrexate therapy, the implications of which are important especially in resource poor settings with high prevalence of folate deficiency. PMID:27168705

  19. Immunomodulatory Effects of the Agaricus blazei Murrill-Based Mushroom Extract AndoSan in Patients with Multiple Myeloma Undergoing High Dose Chemotherapy and Autologous Stem Cell Transplantation: A Randomized, Double Blinded Clinical Study

    PubMed Central

    Tierens, Anne; Caers, Jo; Binsfeld, Marilene; Olstad, Ole Kristoffer; Trøseid, Anne-Marie Siebke; Wang, Junbai; Tjønnfjord, Geir Erland; Hetland, Geir

    2015-01-01

    Forty patients with multiple myeloma scheduled to undergo high dose chemotherapy with autologous stem cell support were randomized in a double blinded fashion to receive adjuvant treatment with the mushroom extract AndoSan, containing 82% of Agaricus blazei Murrill (19 patients) or placebo (21 patients). Intake of the study product started on the day of stem cell mobilizing chemotherapy and continued until the end of aplasia after high dose chemotherapy, a period of about seven weeks. Thirty-three patients were evaluable for all study endpoints, while all 40 included patients were evaluable for survival endpoints. In the leukapheresis product harvested after stem cell mobilisation, increased percentages of Treg cells and plasmacytoid dendritic cells were found in patients receiving AndoSan. Also, in this group, a significant increase of serum levels of IL-1ra, IL-5, and IL-7 at the end of treatment was found. Whole genome microarray showed increased expression of immunoglobulin genes, Killer Immunoglobulin Receptor (KIR) genes, and HLA genes in the Agaricus group. Furthermore, AndoSan displayed a concentration dependent antiproliferative effect on mouse myeloma cells in vitro. There were no statistically significant differences in treatment response, overall survival, and time to new treatment. The study was registered with Clinicaltrials.gov NCT00970021. PMID:25664323

  20. Optimal dosing of cancer chemotherapy using model predictive control and moving horizon state/parameter estimation.

    PubMed

    Chen, Tao; Kirkby, Norman F; Jena, Raj

    2012-12-01

    Model predictive control (MPC), originally developed in the community of industrial process control, is a potentially effective approach to optimal scheduling of cancer therapy. The basis of MPC is usually a state-space model (a system of ordinary differential equations), whereby existing studies usually assume that the entire states can be directly measured. This paper aims to demonstrate that when the system states are not fully measurable, in conjunction with model parameter discrepancy, MPC is still a useful method for cancer treatment. This aim is achieved through the application of moving horizon estimation (MHE), an optimisation-based method to jointly estimate the system states and parameters. The effectiveness of the MPC-MHE scheme is illustrated through scheduling the dose of tamoxifen for simulated tumour-bearing patients, and the impact of estimation horizon and magnitude of parameter discrepancy is also investigated. PMID:22739208

  1. Anticancer chemotherapy

    SciTech Connect

    Weller, R.E.

    1988-10-01

    Despite troubled beginnings, anticancer chemotherapy has made significant contribution to the control of cancer in man, particularly within the last two decades. Early conceptual observations awakened the scientific community to the potentials of cancer chemotherapy. There are now more than 50 agents that are active in causing regression of clinical cancer. Chemotherapy's major conceptual contributions are two-fold. First, there is now proof that patients with overt metastatic disease can be cured, and second, to provide a strategy for control of occult metastases. In man, chemotherapy has resulted in normal life expectancy for some patients who have several types of metastatic cancers, including choriocarcinoma, Burkitt's lymphomas, Wilm's tumor, acute lymphocytic leukemia, Hodgkins disease, diffuse histiocytic lymphoma and others. Anticancer chemotherapy in Veterinary medicine has evolved from the use of single agents, which produce only limited remissions, to the concept of combination chemotherapy. Three basic principles underline the design of combination chemotherapy protocols; the fraction of tumor cell killed by one drug is independent of the fraction killed by another drug; drugs with different mechanisms of action should be chosen so that the antitumor effects will be additive; and since different classes of drugs have different toxicities the toxic effects will not be additive.

  2. High-dose Extended-Field Irradiation and High-Dose-Rate Brachytherapy With Concurrent Chemotherapy for Cervical Cancer With Positive Para-Aortic Lymph Nodes

    SciTech Connect

    Kim, Young Seok; Kim, Jong Hoon; Ahn, Seung Do; Lee, Sang-wook; Shin, Seong Soo; Nam, Joo-Hyun; Kim, Young-Tak; Kim, Yong-Man; Kim, Jong-Hyeok; Choi, Eun Kyung

    2009-08-01

    Purpose: To determine the efficacy and toxicity of extended-field radiotherapy (RT) with concurrent platinum-based chemotherapy in patients with uterine cervical carcinoma and positive para-aortic nodes. Methods and Materials: We retrospectively reviewed the results for 33 women with Stage IB-IVB cervical cancer. Each patient had received 59.4 Gy, including a three-dimensional conformal boost to the para-aortic lymph nodes and 41.4-50.4 Gy of external beam radiotherapy to the pelvis. Each patient also underwent six or seven applications of high-dose-rate brachytherapy (median, 5 Gy to point A at each session). Results: The median follow-up period of surviving patients was 39 months. The most common acute toxicity was hematologic, observed in 23 women. Severe acute and late gastrointestinal toxicity was observed in 3 and 4 patients, respectively. More than three-quarters of patients showed a complete response, encompassing the primary mass, metastatic pelvic, and para-aortic lymph nodes. Of the 33 women, 15 had no evidence of disease, 6 had persistent disease, 4 developed in-field failures, and 6 developed distant failures. The 5-year overall and disease-free survival rate was 47% and 42%, respectively. Conclusion: Concurrent chemoradiotherapy with extended-field radiotherapy is feasible in women with uterine cervical carcinoma and positive para-aortic lymph nodes, with acceptable late morbidity and a high survival rate, although it was accompanied by substantial acute toxicity.

  3. Allogeneic stem cell transplantation as initial salvage for patients with acute myeloid leukemia refractory to high-dose cytarabine-based induction chemotherapy.

    PubMed

    Jabbour, Elias; Daver, Naval; Champlin, Richard; Mathisen, Michael; Oran, Betul; Ciurea, Stefan; Khouri, Issa; Cornelison, A Megan; Ghanem, Hady; Cardenas-Turanzas, Marylou; Popat, Uday; Ravandi, Farhad; Giralt, Sergio; Garcia-Manero, Guillermo; Cortes, Jorge; Kantarjian, Hagop; de Lima, Marcos

    2014-04-01

    Outcomes of patients with acute myeloid leukemia (AML) who are refractory to high-dose Cytarabine (HiDAC)-based induction are dismal. Allogeneic hematopoietic stem cell transplantation (AHSCT) as initial salvage may be effective and potentially superior to conventional salvage chemotherapy. Eighteen percent (285 of 1597) of AML patients were primary refractory to HiDAC-based regimens at the MD Anderson Cancer Center between 1995 and 2009. AHSCT was the initial salvage in 28 cases. These patients were compared against 149 patients who received salvage chemotherapy, but never received AHSCT. Patients receiving salvage chemotherapy were older, had higher bone marrow blasts percentage, and higher incidence of unfavorable cytogenetics (P < 0.001). Median time from induction to AHSCT was 76 days. Objective response was achieved in 23 of 28 patients (82%) undergoing AHSCT. The incidence of grade III/IV acute and chronic graft versus-host-disease was 11% and 29%, respectively. Median follow up for living patients is 80 months. Median overall survival (OS) was 15.7 months and 2.9 months for AHSCT and chemotherapy, respectively (P < 0.001); the 3-year OS rates were 39% and 2%, respectively. ASHCT as initial salvage therapy was identified as an independent prognostic factor for survival in multivariate analysis (HR = 3.03; P < 0.001). Initial salvage therapy with AHSCT in patients with primary HiDAC refractory AML is feasible and may yield superior outcomes to salvage chemotherapy. PMID:24375514

  4. Allogeneic Stem Cell transplantation as Initial Salvage for Patients with Acute Myeloid Leukemia Refractory to High-Dose Cytarabine-Based Induction Chemotherapy

    PubMed Central

    Jabbour, Elias; Daver, Naval; Champlin, Richard; Mathisen, Michael; Oran, Betul; Ciurea, Stefan; Khouri, Issa; Cornelison, A Megan; Ghanem, Hady; Cardenas-Turanzas, Marylou; Popat, Uday; Ravandi, Farhad; Giralt, Sergio; Garcia-Manero, Guillermo; Kantarjian, Hagop; de Lima, Marcos

    2014-01-01

    Purpose Outcomes of patients with acute myeloid leukemia (AML) who are refractory to high-dose Cytarabine (HiDAC)-based induction are dismal. Allogeneic hematopoietic stem cell transplantation (AHSCT) as initial salvage may be effective and potentially superior to conventional salvage chemotherapy. Methods Eighteen percent (285 of 1597) of AML patients were primary refractory to HiDAC-based regimens at the MD Anderson Cancer Center between 1995 and 2009. AHSCT was the initial salvage in 28 cases. These patients were compared against 149 patients who received salvage chemotherapy, but never received AHSCT. Results Patients receiving salvage chemotherapy were older, had higher bone marrow blasts percentage, and higher incidence of unfavorable cytogenetics (P<0.001). Median time from induction to AHSCT was 76 days. Objective response was achieved in 23 of 28 patients (82%) undergoing AHSCT. The incidence of grade III/IV acute and chronic graft versus-host-disease was 11% and 29%, respectively. Median follow up for living patients is 80 months. Median overall survival (OS) was 15.7 months and 2.9 months for AHSCT and chemotherapy, respectively (P<0.001); the 3-year OS rates were 39% and 2%, respectively. ASHCT as initial salvage therapy was identified as an independent prognostic factor for survival in multivariate analysis (HR = 3.03; P < 0.001). Conclusion Initial salvage therapy with AHSCT in patients with primary HiDAC refractory AML is feasible and may yield superior outcomes to salvage chemotherapy. PMID:24375514

  5. Semagacestat pharmacokinetics are not significantly affected by formulation, food, or time of dosing in healthy participants.

    PubMed

    Willis, Brian A; Zhang, Wei; Ayan-Oshodi, Mosun; Lowe, Stephen L; Annes, William F; Sirois, Paul J; Friedrich, Stuart; de la Peña, Amparo

    2012-06-01

    Semagacestat, a γ-secretase inhibitor, reduces formation of amyloid beta peptide. Two single-dose (140 mg), open-label, randomized, 3-period, crossover studies evaluated the effect of formulation, food, and time of dosing on the pharmacokinetics and pharmacodynamics of semagacestat in healthy participants. The first study (n = 14) compared tablet to capsules. For all formulations, the median time to maximum plasma concentration (t(max)) was generally 1.0 hour. Plasma elimination was rapid, with a half-life of approximately 2.5 hours. Tablet form II bioavailability (F) relative to capsule was approximately 100% (F = 1.03 [90% confidence interval (CI), 0.96-1.10]). In the second study, participants (n = 27) received semagacestat either fed or fasting in the morning or fasting in the evening. No significant change in exposure (AUC(0-∞) [area under the concentration-time curve from 0 to infinity] ratio = 1.02, [90% CI, 0.990-1.05]) occurred with food, whereas maximum plasma concentration (C(max)) declined approximately 15%, and median t(max) was delayed to 1.5 hours. Time of dosing made no significant difference in AUC(0-∞), C(max), or t(max) (AUC(0-∞) ratio 1.01, [90% CI, 0.975-1.04]). No clinically significant safety concerns occurred in either study. Accordingly, semagacestat may be dosed without regard to formulation, food, or time of administration. PMID:21724950

  6. Prognostic and Predictive Significance of MYC and KRAS Alterations in Breast Cancer from Women Treated with Neoadjuvant Chemotherapy

    PubMed Central

    de Souza, Carolina Rosal Teixeira; Montenegro, Raquel Carvalho; Rey, Juan Antonio; Carvalho, Antônio Alberto; Assumpção, Paulo Pimentel; Khayat, André Salim; Pinto, Giovanny Rebouças; Demachki, Sâmia; de Arruda Cardoso Smith, Marília; Burbano, Rommel Rodríguez

    2013-01-01

    Breast cancer is a complex disease, with heterogeneous clinical evolution. Several analyses have been performed to identify the risk factors for breast cancer progression and the patients who respond best to a specific treatment. We aimed to evaluate whether the hormone receptor expression, HER2 and MYC genes and their protein status, and KRAS codon 12 mutations may be prognostic or predictive biomarkers of breast cancer. Protein, gene and mutation status were concomitantly evaluated in 116 breast tumors from women who underwent neoadjuvant chemotherapy with doxorubicin plus cyclophosphamide. We observed that MYC expression was associated with luminal B and HER2 overexpression phenotypes compared to luminal A (p<0.05). The presence of MYC duplication or polysomy 8, as well as KRAS mutation, were also associated with the HER2 overexpression subtype (p<0.05). MYC expression and MYC gain were more frequently observed in early-onset compared to late-onset tumors (p<0.05). KRAS mutation was a risk factor of grade 3 tumors (p<0.05). A multivariate logistic regression demonstrated that MYC amplification defined as MYC/nucleus ratio of ≥2.5 was a protective factor for chemotherapy resistance. On the other hand, age and grade 2 tumors were a risk factor. Additionally, luminal B, HER2 overexpression, and triple-negative tumors presented increased odds of being resistant to chemotherapy relative to luminal A tumors. Thus, breast tumors with KRAS codon 12 mutations seem to present a worse prognosis. Additionally, MYC amplification may help in the identification of tumors that are sensitive to doxorubicin plus cyclophosphamide treatment. If confirmed in a large set of samples, these markers may be useful for clinical stratification and prognosis. PMID:23555992

  7. Treatment of recurrent primitive neuroectodermal tumors (PNET) in children and adolescents with high-dose chemotherapy (HDC) and stem cell support: results of the HITREZ 97 multicentre trial.

    PubMed

    Bode, U; Zimmermann, M; Moser, O; Rutkowski, S; Warmuth-Metz, M; Pietsch, T; Kortmann, R D; Faldum, A; Fleischhack, G

    2014-12-01

    Early studies with high-dose chemotherapy for treatment of relapsed cerebral PNET had shown modest efficacy but considerable toxicity. The HIT97 national trial tested a nonrandomized but stratified relapse protocol using either intensive chemotherapy, potentially high dose, or oral chemotherapy. 72 patients (59 disseminated) whose primary treatment had been surgery (97 %), radiotherapy (88 %), and/or chemotherapy (95 %) were enrolled in the intensive chemotherapy arm at diagnosis of relapse or resistance. As a window for this study they received two courses of a 96-hour infusion with carboplatin and etoposide. A response (complete or partial remission) was documented by MRI. Responders received two more cycles of this therapy and stem cell collection, before they received HDC (carboplatin, etoposide, thiotepa) and stem cell support. All possibilities of local therapy were to be explored and applied. After two courses of chemotherapy there was a 52 % response rate (41/72 patients). The median PFS and OS for all 72 patients were 11.6 and 21.1 months. Patients with medulloblastoma had a longer PFS and OS (12.6 and 22.6 months) than those with other PNETs (3.1 and 12.3 months). Favourable prognostic features were no new signs of clinical impairment and localised disease at relapse diagnosis. For the 27 patients who received HDC the median PFS and OS were 8.4 and 20.2 months, respectively. HDC did not benefit patients with resistant cerebral PNET and was associated with profound haematological and mucosal toxicity (90-100 % grade III, IV), infections (50 % grade III and IV) and severe ototoxicity (50 % grade III, 12.5 % grade IV). Treatment related mortality was 8 %. There was low long-term survival and only 2/72 patients are in continuous remission. Adding HDC in patients who responded to the initial courses of chemotherapy did not improve survival. Patients with relapsed cerebral PNET who respond to conventional chemotherapy do not profit from further

  8. 16S rRNA gene pyrosequencing reveals shift in patient faecal microbiota during high-dose chemotherapy as conditioning regimen for bone marrow transplantation.

    PubMed

    Montassier, Emmanuel; Batard, Eric; Massart, Sébastien; Gastinne, Thomas; Carton, Thomas; Caillon, Jocelyne; Le Fresne, Sophie; Caroff, Nathalie; Hardouin, Jean Benoit; Moreau, Philippe; Potel, Gilles; Le Vacon, Françoise; de La Cochetière, Marie France

    2014-04-01

    Gastrointestinal disturbances are a side-effect frequently associated with haematological malignancies due to the intensive cytotoxic treatment given in connection with bone marrow transplantation (BMT). However, intestinal microbiota changes during chemotherapy remain poorly described, probably due to the use of culture-based and low-resolution molecular methods in previous studies. The objective of our study was to apply a next generation DNA sequencing technology to analyse chemotherapy-induced changes in faecal microbiota. We included eight patients with non-Hodgkin's lymphoma undergoing one course of BMT conditioning chemotherapy. We collected a prechemotherapy faecal sample, the day before chemotherapy was initiated, and a postchemotherapy sample, collected 1 week after the initiation of chemotherapy. Total DNA was extracted from faecal samples, denaturing high-performance liquid chromatography based on amplification of the V6 to V8 region of the 16S ribosomal RNA (rRNA) gene, and 454-pyrosequencing of the 16 S rRNA gene, using PCR primers targeting the V5 and V6 hypervariable 16S rRNA gene regions were performed. Raw sequence data were screened, trimmed, and filtered using the QIIME pipeline. We observed a steep reduction in alpha diversity and significant differences in the composition of the intestinal microbiota in response to chemotherapy. Chemotherapy was associated with a drastic drop in Faecalibacterium and accompanied by an increase of Escherichia. The chemotherapy-induced shift in the intestinal microbiota could induce severe side effects in immunocompromised cancer patients. Our study is a first step in identifying patients at risk for gastrointestinal disturbances and to promote strategies to prevent this drastic shift in intestinal microbiota. PMID:24402367

  9. Pattern of employment and associated factors in long-term lymphoma survivors 10 years after high-dose chemotherapy with autologous stem cell transplantation.

    PubMed

    Kiserud, C E; Fagerli, U-M; Smeland, K B; Fluge, Ø; Bersvendsen, H; Kvaløy, S; Holte, H; Dahl, A A

    2016-05-01

    Background This study examined employment patterns and associated factors in lymphoma survivors treated with high-dose chemotherapy with autologous stem cell transplantation (HDT-ASCT) from diagnosis to a follow-up survey at a mean of 10 years after HDT-ASCT. Patients and methods All lymphoma survivors aged ≥18 years at HDT-ASCT in Norway from 1987 to 2008, and alive at the end of 2011 were eligible for this cross-sectional study performed in 2012/2013. Participants completed a mailed questionnaire. Job status was dichotomized as either employed (paid work) or not-employed (disability and retirement pension, on economic support, home-makers, or students). Results The response rate was 78%, and the sample (N = 312) contained 60% men. Mean age at HDT-ASCT was 44.3 and at survey 54.0 years. At diagnosis 85% of survivors were employed, 77% before and 77% after HDT-ASCT, and 58% at follow-up. Forty seven percent of the survivors were employed at all time points. The not-employed group at survey was significantly older and included significantly more females than the employed group. No significant between-group differences were observed for lymphoma-related variables. Fatigue, mental distress and type D personality were significantly higher among those not-employed, while quality of life was significantly lower compared to the employed group. Older age at survey, being female, work ability and presence of type D personality remained significantly related to being not-employed at survey in the multivariable analysis. Conclusions Our findings show that not-employed long-term survivors after HDT-ASCT for lymphoma have more comorbidity, cognitive problems and higher levels of anxiety/depression than employed survivors. These factors should be checked and eventually treated in order to improve work ability. PMID:27123741

  10. Significance of certain rustler aquifer parameters for predicting long-term radiation doses from WIPP

    SciTech Connect

    Wofsy, C

    1980-09-01

    This report considers some aspects of the radionuclide transport modeling presented in documents published by the US Department of Energy (DOE) regarding the Waste Isolation Pilot Plant (WIPP) nuclear waste repository proposed for development in Southeastern New Mexico. The radionuclide transport modeling is used to predict worst possible consequences of a WIPP repository breach event in which waste enters groundwater. The aim of this report is to determine whether plausible changes in the parameters used by DOE to describe the flow of groundwater near the WIPP site could result in: (a) significantly faster radionuclide movement in groundwater; and (b) significantly higher concentrations of radionuclides in Pecos River water and correspondingly higher radiation doses than predicted by DOE. The conclusion reached is that while plausible changes in hydrologic conditions and waste-rock interactions might result in a significant reduction in the time it takes for radionuclides to reach the Pecos River, the shorter travel times do not result in significant increases in the estimated concentrations of radionuclides in the Pecos River nor in the radiation doses associated with the use of such water. Other ways in which parameter changes might affect these concentrations and doses are mentioned in the Conclusions section of the report, but are not the subject of this analysis.

  11. Docetaxel in combination with 5-fluorouracil in patients with metastatic breast cancer previously treated with anthracycline-based chemotherapy: a phase I, dose-finding study.

    PubMed

    Lortholary, A; Maillard, P; Delva, R; Boisdron-Celle, M; Perard, D; Vernillet, L; Besenval, M; Gamelin, E

    2000-09-01

    This phase I study evaluated the maximum tolerated dose, dose-limiting toxicity and recommended dose of docetaxel in combination with 5-fluorouracil (5-FU) in patients with metastatic breast cancer previously treated with anthracycline-based chemotherapy. 32 patients received docetaxel at 60, 75, 85 or 100 mg/m(2) by 1-h intravenous (i.v.) infusion, followed, after a 1-h interval, by 5-FU at 250, 350, 500 or 750 mg/m(2)/day by continuous infusion over 5 days every 3 weeks. Dose-limiting stomatitis defined the maximum tolerated dose at a docetaxel dose of 100 mg/m(2) with 5-FU 750 mg/m(2)/day. None of 5 patients treated at the previous dose level (docetaxel 85 mg/m(2) with 5-FU 750 mg/m(2)/day) had a dose-limiting toxicity in the first cycle, and this was, therefore, considered the recommended dose. The combination was generally well tolerated. Grade 4 neutropenia was common (29 patients; 91%), but no patient experienced febrile neutropenia of duration >3 days requiring i.v. antibiotics. An objective response was achieved by 18 patients overall (56%), and in 4 out of 5 patients treated with the determined recommended dose. No pharmacokinetic interaction between docetaxel and 5-fluorouracil was apparent. The activity of docetaxel 85 mg/m(2) with 5-fluorouracil 750 mg/m(2)/day will be explored more extensively in phase II studies of patients with metastatic breast cancer previously treated with anthracycline-based chemotherapy. PMID:10974625

  12. Does the Addition of Involved Field Radiotherapy to High-Dose Chemotherapy and Stem Cell Transplantation Improve Outcomes for Patients With Relapsed/Refractory Hodgkin Lymphoma?

    SciTech Connect

    Kahn, Shannon; Flowers, Christopher; Xu Zhiheng; Esiashvili, Natia

    2011-09-01

    Purpose: To evaluate the value of adding involved field radiotherapy (IFRT) to patients with relapsed/refractory Hodgkin lymphoma (HL) undergoing high-dose chemotherapy (HDCT) and stem cell transplantation (SCT). Methods and Materials: Ninety-two patients with relapsed/refractory HL undergoing HDCT and SCT from 1995 to 2008 were analyzed in a case-control design. Forty-six HL patients treated with IFRT within 2 months of SCT were matched to 46 HL patients who did not receive IFRT based on age, stage at relapse, timing of relapse, histology, and year of SCT. All were evaluated for response, survival, and toxicity with a median followup of 63.5 months. Results: There was a trend for better disease control in patients receiving IFRT. Specifically, 10/46 IFRT patients (22%) relapsed/progressed after SCT compared with 17/46 control patients (37%). Of the failures after IFRT, 70% were inside the radiation field, all in sites of bulky disease. In patients with nonbulky disease, IFRT also resulted in significantly improved outcomes (failure rate 6% vs. 33%, respectively). When stratified by disease bulk, the use of IFRT was found to significantly improve DFS (p = 0.032), but did not affect OS. In addition, IFRT and nonbulky disease were found to be positive prognostic indicators for DFS with hazard ratios of 0.357 (p = 0.032) and 0.383 (p = 0.034), respectively. Grade IV/V toxicities were significantly higher in the IFRT vs. non-IFRT group (28% vs. 2%; p < 0.001), observed only in patients receiving a busulfan-based conditioning regimen. Conclusion: Patients with refractory or relapsed HL undergoing HDCT and SCT have a high risk of relapse in sites of prior disease involvement, especially in sites of bulky disease. The use of IFRT is associated with a lower risk of disease progression in these sites; however bulky disease sites are still difficult to control. Toxicity risk is significant, particularly when busulfan-based conditioning is combined with IFRT, and alternative

  13. Significantly reduced radiation dose to operators during percutaneous vertebroplasty using a new cement delivery device

    PubMed Central

    2014-01-01

    Background Percutaneous vertebroplasy (PVP) might lead to significant radiation exposure to patients, operators, and operating room personnel. Therefore, radiaton exposure is a concern. The aim of this study was to present a remote control cement delivery device and study whether it can reduce dose exposue to operators. Methods After meticulous preoperative preparation, a series of 40 osteoporosis patients were treated with unilateral approach PVP using the new cement delivery divice. We compared levels of fluoroscopic exposure to operator standing on different places during operation. group A: operator stood about 4 meters away from X-ray tube behind the lead sheet. group B: operator stood adjacent to patient as using conventional manual cement delivery device. Results During whole operation process, radiation dose to the operator (group A) was 0.10 ± 0.03 (0.07-0.15) μSv, group B was 12.09 ± 4.67 (10–20) μSv. a difference that was found to be statistically significant (P < 0.001) between group A and group B. Conclusion New cement delivery device plus meticulous preoperative preparation can significantly decrease radiation dose to operators. PMID:25084860

  14. Predictive significance of DNA damage and repair biomarkers in triple-negative breast cancer patients treated with neoadjuvant chemotherapy: An exploratory analysis

    PubMed Central

    Ercolani, Cristiana; Pizzuti, Laura; Lauro, Luigi Di; Sergi, Domenico; Sperati, Francesca; Terrenato, Irene; Dattilo, Rosanna; Botti, Claudio; Fabi, Alessandra; Ramieri, Maria Teresa; Mentuccia, Lucia; Marinelli, Camilla; Iezzi, Laura; Gamucci, Teresa; Natoli, Clara; Vitale, Ilio; Barba, Maddalena; Mottolese, Marcella; De Maria, Ruggero; Maugeri-Saccà, Marcello

    2015-01-01

    Response of cancer cells to chemotherapy-induced DNA damage is regulated by the ATM-Chk2 and ATR-Chk1 pathways. We investigated the association between phosphorylated H2AX (γ-H2AX), a marker of DNA double-strand breaks that trigger the ATM-Chk2 cascade, and phosphorylated Chk1 (pChk1), with pathological complete response (pCR) in triple-negative breast cancer (TNBC) patients treated with neoadjuvant chemotherapy. γ-H2AX and pChk1 were retrospectively assessed by immunohistochemistry in a series of pretreatment biopsies related to 66 patients. In fifty-three tumors hormone receptor status was negative in both the diagnostic biopsies and residual cancers, whereas in 13 cases there was a slight hormone receptor expression that changed after chemotherapy. Internal validation was carried out. In the entire cohort elevated levels of γ-H2AX, but not pChk1, were associated with reduced pCR rate (p = 0.009). The association tested significant in both uni- and multivariate logistic regression models (OR 4.51, 95% CI: 1.39–14.66, p = 0.012, and OR 5.07, 95% CI: 1.28–20.09, p = 0.021, respectively). Internal validation supported the predictive value of the model. The predictive ability of γ-H2AX was further confirmed in the multivariate model after exclusion of tumors that underwent changes in hormone receptor status during chemotherapy (OR 7.07, 95% CI: 1.39–36.02, p = 0.018). Finally, in residual diseases a significant decrease of γ-H2AX levels was observed (p < 0.001). Overall, γ-H2AX showed ability to predict pCR in TNBC and deserves larger, prospective studies. PMID:26544894

  15. Fatal hyperammonemia and carbamoyl phosphate synthetase 1 (CPS1) deficiency following high-dose chemotherapy and autologous hematopoietic stem cell transplantation.

    PubMed

    Laemmle, Alexander; Hahn, Dagmar; Hu, Liyan; Rüfenacht, Véronique; Gautschi, Matthias; Leibundgut, Kurt; Nuoffer, Jean-Marc; Häberle, Johannes

    2015-03-01

    Fatal hyperammonemia secondary to chemotherapy for hematological malignancies or following bone marrow transplantation has been described in few patients so far. In these, the pathogenesis of hyperammonemia remained unclear and was suggested to be multifactorial. We observed severe hyperammonemia (maximum 475 μmol/L) in a 2-year-old male patient, who underwent high-dose chemotherapy with carboplatin, etoposide and melphalan, and autologous hematopoietic stem cell transplantation for a neuroblastoma stage IV. Despite intensive care treatment, hyperammonemia persisted and the patient died due to cerebral edema. The biochemical profile with elevations of ammonia and glutamine (maximum 1757 μmol/L) suggested urea cycle dysfunction. In liver homogenates, enzymatic activity and protein expression of the urea cycle enzyme carbamoyl phosphate synthetase 1 (CPS1) were virtually absent. However, no mutation was found in CPS1 cDNA from liver and CPS1 mRNA expression was only slightly decreased. We therefore hypothesized that the acute onset of hyperammonemia was due to an acquired, chemotherapy-induced (posttranscriptional) CPS1 deficiency. This was further supported by in vitro experiments in HepG2 cells treated with carboplatin and etoposide showing a dose-dependent decrease in CPS1 protein expression. Due to severe hyperlactatemia, we analysed oxidative phosphorylation complexes in liver tissue and found reduced activities of complexes I and V, which suggested a more general mitochondrial dysfunction. This study adds to the understanding of chemotherapy-induced hyperammonemia as drug-induced CPS1 deficiency is suggested. Moreover, we highlight the need for urgent diagnostic and therapeutic strategies addressing a possible secondary urea cycle failure in future patients with hyperammonemia during chemotherapy and stem cell transplantation. PMID:25639153

  16. Is Intermediate Radiation Dose Escalation With Concurrent Chemotherapy for Stage III Non–Small-Cell Lung Cancer Beneficial? A Multi-Institutional Propensity Score Matched Analysis

    SciTech Connect

    Rodrigues, George; Oberije, Cary; Senan, Suresh; Tsujino, Kayoko; Wiersma, Terry; Moreno-Jimenez, Marta; Kim, Tae Hyun; Marks, Lawrence B.; Rengan, Ramesh; De Petris, Luigi; Ramella, Sara; DeRuyck, Kim; De Dios, Núria Rodriguez; Warner, Andrew; Bradley, Jeffrey D.; Palma, David A.

    2015-01-01

    Purpose: The clinical benefits and risks of dose escalation (DE) for stage III non–small-cell lung cancer (NSCLC) remain uncertain despite the results from Radiation Therapy Oncology Group (RTOG) protocol 0617. There is significant heterogeneity of practice, with many clinicians prescribing intermediate dose levels between the 0617 study arms of 60 and 74 Gy. This study investigated whether this strategy is associated with any survival benefits/risks by analyzing a large multi-institutional database. Methods and Materials: An individual patient database of stage III NSCLC patients treated with radical intent concurrent chemoradiation therapy was created (13 institutions, n=1274 patients). Patients were divided into 2 groups based on tumor Biological Effective Dose at 10 Gy (BED 10): those receiving standard dose (SD; n=552), consisting of 72Gy ≤ BED 10 ≤ 76.8 Gy (eg 60-64 Gy/30-32 fractions [fr]), and those receiving intermediate dose (ID; n=497), consisting of 76.8Gy < BED 10 < 100.8 Gy (eg >64 Gy/32 fr and <74 Gy/37 fr), with lower-dose patients (n=225) excluded from consideration. Patients were then matched using propensity scores, leading to 2 matched groups of 196 patients. Outcomes were compared using various statistics including interquartile range (IQR), Kaplan-Meier curves, and adjusted Cox regression analysis. Results: Matched groups were found to be balanced except for N stage (more N3 disease in SD), median treatment year (SD in 2003; ID in 2007), platinum and taxane chemotherapy (SD in 28%; ID in 39%), and median follow-up (SD were 89 months; ID were 40 months). Median dose fractionation was 60 Gy/30 fr in SD (BED 10 IQR: 72.0-75.5 Gy) and 66 Gy/33 fr (BED 10 IQR: 78.6-79.2 Gy) in ID. Survival curves for SD and ID matched cohorts were statistically similar (P=.27); however, a nonstatistically significant trend toward better survival for ID was observed after 15 months (median survival SD: 19.3 months; ID: 21.0

  17. Post-chemotherapy surgery in advanced non-seminomatous germ-cell testicular tumours: the significance of histology with particular reference to differentiated (mature) teratoma.

    PubMed Central

    Tait, D.; Peckham, M. J.; Hendry, W. F.; Goldstraw, P.

    1984-01-01

    Of a total of 307 patients treated with chemotherapy for advanced non-seminomatous germ-cell testicular tumours between 1976 and 1983, 73 (23.8%) had masses excised after treatment. Resected tissue showed residual malignancy in 16 (22%), fibrosis and necrosis in 25 (34%) and differentiated (mature teratoma) in 32 (44%). Of the 16 patients with tumour only 7 (44%) are alive and disease-free compared with 21/25 (84%) and 27/32 (84%) for fibrosis/necrosis and differentiated teratoma respectively. In addition to histological evidence of residual tumour, elevated serum markers at the time of surgery and/or incomplete excision of residual masses were adverse prognostic features. Of 12 patients with differentiated teratoma or fibrosis who had incomplete resections or densely adherent masses excised with difficulty, 7 subsequently relapsed. The majority of differentiated teratoma patients (75%) had evidence of differentiation in their primary tumours; 88% showed cystic change in metastases and almost one-third showed an increase in the size of metastases during chemotherapy. The data suggest that post-chemotherapy surgery may have a therapeutic as well as a diagnostic role and that complete excision of residual disease should be attempted even if resection at one site has shown either fibrosis or differentiated teratoma. The significance of these findings in relation to treatment induced differentiation is discussed. PMID:6093838

  18. A phase I clinical trial of dose escalation of lobaplatin in combination with fixed-dose docetaxel for the treatment of human solid tumours that had progressed following chemotherapy.

    PubMed

    Peng, Yu; Liu, Yue-E; Ren, Xiao-Can; Chen, Xue-Ji; Su, Hui-Ling; Zong, Jie; Feng, Zeng-Li; Wang, Dong-Ying; Lin, Qiang; Gao, Xian-Shu

    2015-01-01

    In this study, the maximum tolerated dose (MTD) of lobaplatin (LBP) when it was combined with docetaxel (TXT) for the treatment of solid tumours that had progressed following chemotherapy was determined, and toxicities to this regimen were evaluated. A modified Fibonacci method was used for the dose escalation of LBP. The patients received TXT (at a fixed dose of 60 mg/m(2)) on day one (d1) and LBP (at an initial tested dose of 30 mg/m(2)) on day two (d2) of a treatment cycle that was repeated every 21 days. Each dose group consisted of at least three cases. In the absence of dose-limiting toxicity (DLT), we proceeded to the next dose group, with a dose increment of 5 mg/m(2) between groups, until DLT occurred. The dose immediately below the dose that produced DLT was regarded as the MTD. The 17 patients examined in this study completed a total of 58 cycles of chemotherapy, and a total of three dose-escalation groups (30 mg/m(2) LBP, 35 mg/m(2) LBP, and 40 mg/m(2) LBP) were established. The main adverse event that was observed was myelosuppression. DLT occurred in four patients, including three patients in the 40 mg/m(2) LBP group and one patient in the 35 mg/m(2) LBP group. In total, three out of the four patients in the 40 mg/m(2) LBP group exhibited DLT. We determined that the treatment administered to the 35 mg/m(2) LBP group represented the MTD. Thus, our phase I trial revealed that the MTD for the tested LBP combination regimen was 35 mg/m(2) LBP and 60 mg/m(2) TXT. This regimen resulted in mild adverse reactions and favourable patient tolerance. Therefore, we recommend the use of these dosages in phase II clinical trials. PMID:25435935

  19. Parathyroid hormone linked to a collagen binding domain (PTH-CBD) promotes hair growth in a mouse model of chemotherapy-induced alopecia in a dose-dependent manner

    PubMed Central

    Katikaneni, Ranjitha; Ponnapakkam, Tulasi; Seymour, Andrew; Sakon, Joshua; Gensure, Robert

    2014-01-01

    Chemotherapy-induced alopecia is a major source of psychological stress in patients undergoing cancer chemotherapy, and can influence treatment decisions. While there is currently no therapy, PTH-CBD, a fusion protein of parathyroid hormone and collagen binding domain, has shown promise in animal models. Objective To determine if there are dose-dependent effects of PTH-CBD on chemotherapy-induced alopecia in a mouse model. Methods C57BL/6J mice were waxed to synchronize hair follicles; treated on day 7 with vehicle or PTH-CBD (100, 320 and 1000 mcg/kg subcutaneous injection); treated on day 9 with vehicle or cyclophosphamide (150 mg/kg i.p.). Mice were photographed every 3–4 days and sacrificed on day 63 for histological analysis. Photographs were quantified by grey scale analysis to assess hair content. Results Mice not receiving chemotherapy showed regrowth of hair 2 weeks following waxing, and normal histology after 2 months. Mice receiving chemotherapy alone showed marked hair loss after chemotherapy, which was sustained for 10 days and was followed by rapid regrowth of a normal coat. Histology revealed rapid cycling dystrophic anagen/catagen follicles. Animals receiving chemotherapy and PTH-CBD showed decreased hair loss and more rapid regrowth of hair than that seen with chemotherapy alone (increased hair growth by grey scale analysis, p<0.05), and the effects were dose dependent. Histologically, hair follicles in animals receiving the highest dose of PTH-CBD were in a quiescent phase, similar to mice which did not receive chemotherapy. Conclusions Single dose subcutaneous administration of PTH-CBD showed dose-dependent effects in minimizing hair loss and speeding recovery from chemotherapy-induced alopecia. PMID:24710191

  20. Salvage therapy with high-dose chemotherapy and peripheral blood stem cell transplant in patients with primary mediastinal nonseminomatous germ cell tumors.

    PubMed

    Suleiman, Yaman; Siddiqui, Bilal K; Brames, Mary J; Abonour, Rafat; Einhorn, Lawrence H

    2013-01-01

    Salvage therapy with high-dose chemotherapy (HDCT) and bone marrow transplant (BMT) or peripheral blood stem cell transplant (PBSCT) has curative potential in patients with recurrent germ cell tumor. However, patients with primary mediastinal nonseminomatous germ cell tumors (PMNSGCTs) have had poor results with any form of salvage chemotherapy including HDCT. We switched from BMT to PBSCT in 1996. One hundred sixteen of 184 patients (63%) with recurrent or refractory germ cell tumors treated from 1996 to 2004 were alive and continuously disease-free. PMNSGCTs were excluded from that study because of poor results in the patient population with HDCT and BMTs. In 2006, we resumed treating patients with recurrent PMNSGCT with 2 consecutive courses of HDCT consisting of carboplatin 700 mg/m(2) × 3 plus etoposide 750 mg/m(2) × 3 and each followed by an infusion of autologous peripheral-blood hematopoietic stem cells with a second course 3 to 4 weeks later. Twelve patients were treated: 11 as initial salvage chemotherapy and 1 as fourth-line therapy. Eight of the 12 patients had major thoracic resections at the time of the relapse after initial chemotherapy. Three of the 12 patients achieved complete remission (CR; 10, 15, and 50 months' duration). One patient remains continuously with no evidence of disease (NED) at 50 months. An additional patient is currently NED at 52 months with HDCT and subsequent surgery. Median survival for the 12 patients was 11 months (range, 4-52 months). Results with tandem transplant for recurrent PMNSGCT remain poor compared to primary testis cancer, but durable CR and probable cure can be achieved in a small subset of patients with PMNSGCT. In our opinion, salvage surgical resection if anatomically feasible is the preferred option for patients with PMNSGT progressing after initial chemotherapy. PMID:22892555

  1. Feasibility of radiotherapy after high-dose dense chemotherapy with epirubicin, preceded by dexrazoxane, and paclitaxel for patients with high-risk Stage II-III breast cancer

    SciTech Connect

    De Giorgi, Ugo . E-mail: ugo_degiorgi@yahoo.com; Giannini, Massimo; Frassineti, Luca; Kopf, Barbara; Palazzi, Silvia; Giovannini, Noemi; Zumaglini, Federica; Rosti, Giovanni; Emiliani, Ermanno; Marangolo, Maurizio

    2006-07-15

    Purpose: To verify the feasibility of, and quantify the risk of, pneumonitis from locoregional radiotherapy (RT) after high-dose dense chemotherapy with epirubicin and paclitaxel with peripheral blood progenitor cell support in patients with high-risk Stage II-III breast cancer. Methods and Materials: Treatment consisted of a mobilizing course of epirubicin 150 mg/m{sup 2}, preceded by dexrazoxane (Day 1), paclitaxel 175 mg/m{sup 2} (Day 2), and filgrastim; followed by three courses of epirubicin 150 mg/m{sup 2}, preceded by dexrazoxane (Day 1), paclitaxel 400 mg/m{sup 2} (Day 2), and peripheral blood progenitor cell support and filgrastim, every 16-19 days. After chemotherapy, patients were treated with locoregional RT, which included the whole breast or the chest wall, axilla, and supraclavicular area. Results: Overall, 64 of 69 patients were evaluable. The interval between the end of chemotherapy and the initiation of RT was at least 1.5-2 months (mean 2). No treatment-related death was reported. After a median follow-up of 27 months from RT (range 5-77 months), neither clinically relevant radiation pneumonitis nor congestive heart failure had been reported. Minor and transitory lung and cardiac toxicities were observed. Conclusion: Sequential high doses of epirubicin, preceded by dexrazoxane, and paclitaxel did not adversely affect the tolerability of locoregional RT in breast cancer patients. The risk of pneumonitis was not affected by the use of sequential paclitaxel with an interval of at least 1.5-2 months between the end of chemotherapy and the initiation of RT. Long-term follow-up is needed to define the risk of cardiotoxicity in these patients.

  2. Serum alpha-fetoprotein surge after the initiation of chemotherapy for non-seminomatous testicular cancer has an adverse prognostic significance.

    PubMed Central

    de Wit, R.; Collette, L.; Sylvester, R.; de Mulder, P. H.; Sleijfer, D. T.; ten Bokkel Huinink, W. W.; Kaye, S. B.; van Oosterom, A. T.; Boven, E.; Stoter, G.

    1998-01-01

    It has been recognized that the tumour markers alpha-fetoprotein (AFP) and human chorionic gonadotrophin (HCG) may show a transient elevation after the initiation of chemotherapy in non-seminomatous testicular cancer. We investigated the prognostic importance of these so-called marker surges in a cohort of patients treated with cisplatin combination chemotherapy between 1983 and 1991. A total of 669 patients were studied. Of 352 patients who had an elevated AFP at the start of treatment and for whom we had data at both day 1 and day 8, 101 (29%) had a surge. Of 317 patients for whom we had data for HCG, 80 patients (25%) had a surge. It was found that an AFP surge was a strong adverse prognostic factor for progression [hazard ratio (HR) 2.28, P=0.005]. There was no statistically significant difference in survival (HR 1.65, P=0.13). There was no prognostic significance of a HCG surge, either for progression or for survival. To investigate whether a surge was an independent prognostic factor for progression and survival, multivariate Cox regression models were fitted using the independent prognostic factors for progression and survival and the surge/decline variable. An AFP surge was retained in the final model for progression. A HCG surge was of no prognostic importance for progression or survival. We conclude that an AFP surge has an adverse prognostic significance, independent of pretreatment characteristics. PMID:9823978

  3. Pigment epithelium-derived factor expression prolongs survival and enhances the cytotoxicity of low-dose chemotherapy in castration-refractory prostate cancer

    PubMed Central

    Nelius, T; Martinez-Marin, D; Hirsch, J; Miller, B; Rinard, K; Lopez, J; de Riese, W; Filleur, S

    2014-01-01

    as possible mechanism and marker, respectively. As well, both PEDF–CTX-10 mg/kg and PEDF–DTX-5 mg/kg prolonged significantly the survival of tumor-bearing mice compared with single treatments. Metastases were reduced in PEDF–DTX-5 mg/kg compared with other treatments, suggesting that PEDF–DTX delayed metastases formation. Our results advocate that PEDF/low-dose chemotherapy may represent a new therapeutic alternative for CRPC. PMID:24810046

  4. Longitudinal effects of high-dose chemotherapy and autologous stem cell transplantation on quality of life in the treatment of metastatic breast cancer.

    PubMed

    Carlson, L E; Koski, T; Glück, S

    2001-05-01

    This study determined the effects of high-dose chemotherapy (HDCT) with autologous blood stem cell transplantation (ASCT) on quality of life (QL) in women with metastatic breast cancer prior to, and during treatment, and up to 1-year post-ASCT. Thirty-three women diagnosed with metastatic breast cancer participated in a phase 1 clinical trial of a new combination of cyclophosphamide (CTX) and mitoxantrone (MXT), with dose escalation of paclitaxel. Longitudinal QL data were collected using the functional living index-cancer (FLIC) and symptom scales at seven time periods: pre-induction chemotherapy (CT), post-induction CT, post-high dose CT (HDCT), and at 3, 6, 9 and 12 months post-ASCT. FLIC scores indicated that the worst problems for patients were feelings of hardship on themselves and their families, followed by psychological functioning and physical functioning problems. The time around diagnosis of the metastatic disease and following HDCT were the worst times for all levels of quality of life, but anxiety and depression symptoms continued to increase in severity across the entire follow-up period. The symptoms that were most problematic were worry about the future, loss of sexual interest, anxiety about the treatment, general worrying, and joint pain. These data highlight the problems that women with metastatic breast cancer encounter at different stages of the disease and treatment process, and can be used to tailor psychosocial interventions appropriate for treating the relevant issues at different points in time. PMID:11436111

  5. Tandem high-dose chemotherapy strategy as first-line treatment of primary disseminated multifocal Ewing sarcomas in children, adolescents and young adults.

    PubMed

    Loschi, S; Dufour, C; Oberlin, O; Goma, G; Valteau-Couanet, D; Gaspar, N

    2015-08-01

    The prognosis of primary disseminated multifocal metastatic Ewing's sarcoma (PDMES) is poor even if a slight improvement has been achieved with high-dose alkylating agent-containing chemotherapy. To enhance treatment efficacy, we assessed the feasibility, safety and efficacy of a tandem high-dose chemotherapy (HDC) regimen. In a single institution, patients with PDMES received six courses of vincristine/ifosfamide/doxorubicin/etoposide induction therapy, followed by high-dose thiotepa, and then melphalan-busulfan, 8 weeks apart. Surgical resection of primary tumour was carried out between the two HDC regimens and 70 days after the last HDC regimen for post-operative radiotherapy or irradiation alone. From October 2002 to 2009, 13 of the 18 consecutive patients with PDMES (72%) received the full treatment programme. The other five patients experienced early progression and died. Among the 13 patients, 11 relapsed after the end of the treatment programme within 6 months (2.2-11.9) from end of therapy. Only two patients are still alive in first complete remission after 9 years. The 3-year event-free survival (EFS) and overall survival (OS) rates were 11 and 22%, respectively. The median EFS and OS duration from the diagnosis were 13.4 and 17.3 months, respectively. Neither major complications nor treatment-related death occurred. The tandem-HDC regimen was feasible, with expected side effects, but it did not improve the outcome of patients with PDMES. PMID:26030048

  6. 5-Azacitidine Monotherapy Followed by Related Haploidentical Hematopoietic Stem Cell Transplantation Achieves Durable Remission in a Pediatric Patient With Acute Undifferentiated Leukemia Refractory to High-Dose Chemotherapy.

    PubMed

    Polishchuk, Veronika; Khazal, Sajad; Berulava, Giorgi; Roth, Michael; Mahadeo, Kris M

    2016-06-01

    Patients with acute leukemias of undifferentiated lineage (AUL) generally have guarded prognosis. Here, we describe the first reported pediatric patient with AUL refractory to high-dose chemotherapy who achieved clinical remission with ALL maintenance therapy and 5-azacitidine. His induction remission was followed by consolidation with reduced toxicity haploidentical hematopoietic stem cell transplant (HSCT). At 9 months post-HSCT, the patient is alive and in remission. This combination therapy of remission induction with ALL maintenance therapy and 5-azacitidine and consolidation with reduced toxicity haploidentical HSCT is novel and promising for patients who lack conventional donors and are not candidates for myeloablative therapy. PMID:26914221

  7. Adjuvant high-dose chemotherapy with autologous hematopoietic stem cell support for high-risk primary breast cancer: results from the Italian national registry.

    PubMed

    Pedrazzoli, Paolo; Martinelli, Giovanni; Gianni, Alessandro Massimo; Da Prada, Gian Antonio; Ballestrero, Alberto; Rosti, Giovanni; Frassineti, Giovanni Luca; Aieta, Michele; Secondino, Simona; Cinieri, Saverio; Fedele, Roberta; Bengala, Carmelo; Bregni, Marco; Grasso, Donatella; De Giorgi, Ugo; Lanza, Francesco; Castagna, Luca; Bruno, Barbara; Martino, Massimo

    2014-04-01

    The efficacy of high-dose chemotherapy (HDC) and autologous hemopoietic progenitor cell transplantation (AHPCT) for breast cancer (BC) patients has been an area of intense controversy among the medical oncology community. The aim of this study was to assess toxicity and efficacy of this procedure in a large cohort of high-risk primary BC patients who underwent AHPCT in Italy. A total of 1183 patients receiving HDC for high-risk BC (HRBC) (>3 positive nodes) were identified in the Italian registry. The median age was 46 years, 62% of patients were premenopausal at treatment, 60.1% had endocrine-responsive tumors, and 20.7% had a human epidermal growth factor receptor 2 (HER2)-positive tumor. The median number of positive lymph nodes (LN) at surgery was 15, with 71.5% of patients having ≥ 10 positive nodes. Seventy-three percent received an alkylating agent-based HDC as a single procedure, whereas 27% received epirubicin or mitoxantrone-containing HDC, usually within a multitransplantation program. The source of stem cells was peripheral blood in the vast majority of patients. Transplantation-related mortality was .8%, whereas late cardiac and secondary tumor-related mortality were around 1%, overall. With a median follow-up of 79 months, median disease-free and overall survival (OS) in the entire population were 101 and 134 months, respectively. Subgroup analysis demonstrated that OS was significantly better in patients with endocrine-responsive tumors and in patients receiving multiple transplantation procedures. HER2 status did not affect survival probability. The size of the primary tumor and number of involved LN negatively affected OS. Adjuvant HDC with AHPCT has a low mortality rate and provides impressive long-term survival rates in patients with high-risk primary BC. Our results suggest that this treatment modality should be proposed in selected HRBC patients and further investigated in clinical trials. PMID:24374214

  8. Long-Term Follow-Up of Dose-Adapted and Reduced-Field Radiotherapy With or Without Chemotherapy for Central Nervous System Germinoma

    SciTech Connect

    Jensen, Ashley W.; Issa Laack, Nadia N.; Buckner, Jan C.; Schomberg, Paula J.; Wetmore, Cynthia J.; Brown, Paul D.

    2010-08-01

    Purpose: To update our institutional experience with neoadjuvant chemotherapy and minimized radiotherapy vs. radiation monotherapy for intracranial germinoma. Methods and Materials: We retrospectively reviewed records of 59 patients with diagnosis of primary intracranial germinoma between 1977 and 2007. Treatment was irradiation alone or neoadjuvant platinum-based chemotherapy and local irradiation (initial tumor plus margin) for patients with localized complete response and reduced-dose craniospinal irradiation for others. Results: For the chemoradiotherapy group (n = 28), median follow-up was 7 years. No patient died. The freedom from progression (FFP) rate was 88% at 5 years and 80% at 10 years. In 4 patients, disease recurred 1.1 to 6.8 years after diagnosis. All were young male patients who received 30.6 Gy to local fields after complete response to chemotherapy. The FFP rate was 88% for local irradiation vs. 100% for more extensive fields (p = .06). For the radiotherapy-alone group (n = 31), median follow-up was 15 years. Overall and disease-free survival rates were 93% and 93% at 5 years and 90% and 87% at 15 years. In 5 patients, disease recurred 1.1 to 4.9 years after diagnosis. Most patients in this group were young men 18 to 23 years of age with suprasellar primary disease treated with about 50 Gy to local fields. The FFP rate was 44% for local irradiation vs. 100% for more extensive fields (p < .01). Conclusions: The addition of neoadjuvant chemotherapy to local-field radiotherapy reduced central nervous system cancer recurrence when high-risk patients were excluded by thorough pretreatment staging. There was trend toward improved central nervous system tumor control when larger fields (whole brain, whole ventricle, or craniospinal axis) were used.

  9. Chemotherapy-Related Neurotoxicity.

    PubMed

    Taillibert, Sophie; Le Rhun, Emilie; Chamberlain, Marc C

    2016-09-01

    Chemotherapy may have detrimental effects on either the central or peripheral nervous system. Central nervous system neurotoxicity resulting from chemotherapy manifests as a wide range of clinical syndromes including acute, subacute, and chronic encephalopathies, posterior reversible encephalopathy, acute cerebellar dysfunction, chronic cognitive impairment, myelopathy, meningitis, and neurovascular syndromes. These clinical entities vary by causative agent, degree of severity, evolution, and timing of occurrence. In the peripheral nervous system, chemotherapy-induced peripheral neuropathy (CIPN) and myopathy are the two main complications of chemotherapy. CIPN is the most common complication, and the majority manifest as a dose-dependent length-dependent sensory axonopathy. In severe cases of CIPN, the dose of chemotherapy is reduced, the administration delayed, or the treatment discontinued. Few treatments are available for CIPN and based on meta-analysis, duloxetine is the preferred symptomatic treatment. Myopathy due to corticosteroid use is the most frequent cause of muscle disorders in patients with cancer. PMID:27443648

  10. Early discharge after high dose chemotherapy is safe and feasible: a prospective evaluation of 6 years of home care.

    PubMed

    Mank, Arno P M; Schoonenberg, Charlot; Bleeker, Kim; Heijmenberg, Susanne; Heer, Koen de; van Oers, Marinus H J; Kersten, Marie José

    2015-07-01

    A single-center, prospective, non-randomized clinical study was performed to examine the safety and feasibility of early discharge in patients undergoing consolidation chemotherapy for acute leukemia, or autologous stem cell transplant for lymphoma or multiple myeloma. Patients were discharged into ambulatory care the day after the last chemotherapy administration and were subsequently seen at the ambulatory care unit three times a week. One hundred and one of 224 patients were ineligible for the program, mostly because of their medical situation, the lack of a caregiver or the travel time to the hospital. The remaining 123 patients were able to spend more than 70% of the time at home. In 44% of cycles they were never readmitted. This study demonstrates the safety, feasibility and benefits of managing carefully selected patients. Patients and their caregivers felt safe and comfortable at home, and the vast majority preferred home care to in-hospital treatment. PMID:25330445

  11. Clinical Significance of Long Non-Coding RNA CASC8 rs10505477 Polymorphism in Lung Cancer Susceptibility, Platinum-Based Chemotherapy Response, and Toxicity

    PubMed Central

    Hu, Lei; Chen, Shu-Hui; Lv, Qiao-Li; Sun, Bao; Qu, Qiang; Qin, Chong-Zhen; Fan, Lan; Guo, Ying; Cheng, Lin; Zhou, Hong-Hao

    2016-01-01

    Long non-coding RNA (lncRNA) CASC8 rs10505477 polymorphism has been identified to be related to risk of many kinds of cancers, such as colorectal cancer, gastric cancer, and invasive ovarian cancer, and it may be involved in the prognosis of gastric cancer patients who have received platinum-based chemotherapy after surgical treatment. So far, there is no study investigating the clinical significance of lncRNA CASC8 rs10505477 in lung cancer susceptibility and treatment. In this study, we genotyped 498 lung cancer patients and 213 healthy control subjects to explore the correlation between the rs10505477 polymorphism and lung cancer risk in a Chinese population. Among the 498 patients, 467 were selected for the chemotherapy response and toxicity study. We found that the single nucleotide polymorphisms (SNP) rs10505477 was greatly related to lung cancer risk in male and adenocarcinoma subgroups in recessive model (adjusted OR = 0.51, 95%CI = 0.29–0.90, p = 0.02; adjusted OR = 0.52, 95%CI = 0.30–0.89, p = 0.02, respectively). It was also closely correlated with platinum-based chemotherapy response in dominant model (adjusted OR = 1.58, 95%CI = 1.05–2.39, p = 0.03). Additionally, we observed that CASC8 rs10505477 polymorphism was significantly relevant to severe hematologic toxicity in non-small-cell lung cancer (NSCLC) subgroup in dominant model (adjusted OR = 0.59, 95%CI = 0.35–0.98, p = 0.04) and in additive model (adjusted OR = 0.62, 95%CI = 0.43–0.90, p = 0.01). Furthermore, it was found that rs10505477 polymorphism was greatly associated with gastrointestinal toxicity in SCLC and cisplatin subgroups in dominant model (adjusted OR = 7.82, 95%CI = 1.36–45.07, p = 0.02; adjusted OR = 1.94, 95%CI = 1.07–3.53, p = 0.03, respectively). Thus, lncRNA CASC8 rs10505477 could serve as a possible risk marker for diagnosing lung cancer, and could be used to forecast the response and toxicity of platinum-based treatment in lung cancer patients. PMID:27249003

  12. Strategies to eradicate minimal residual disease in small cell lung cancer: high-dose chemotherapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination.

    PubMed

    Krug, L M; Grant, S C; Miller, V A; Ng, K K; Kris, M G

    1999-10-01

    In the last 25 years, treatment for small cell lung cancer (SCLC) has improved with advances in chemotherapy and radiotherapy. Standard chemotherapy regimens can yield 80% to 90% response rates and some cures when combined with thoracic irradiation in limited-stage patients. Nonetheless, small cell lung cancer has a high relapse rate due to drug resistance; this has resulted in poor survival for most patients. Attacking this problem requires a unique approach to eliminate resistant disease remaining after induction therapy. This review will focus on three potential strategies: high-dose chemotherapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination. PMID:10566613

  13. Significant impact on effective doses received during commercial flights calculated using the new ICRP radiation weighting factors.

    PubMed

    Chen, Jing; Mares, Vladimir

    2010-01-01

    This note discusses the significant impact on effective doses received during commercial flights calculated using the new International Commission on Radiological Protection (ICRP) radiation weighting factors. It also provides an update on adult effective doses given in a previous article in Health Physics when the old ICRP radiation weighting factors were used. PMID:19959953

  14. Significant effects of mild endogenous hormonal changes in humans: considerations for low-dose testing.

    PubMed Central

    Brucker-Davis, F; Thayer, K; Colborn, T

    2001-01-01

    We review the significant and adverse health effects that can occur with relatively small endogenous hormonal changes in pubertal and adult humans. We discuss the effects of hormonal changes that occur within normal physiologic ranges--such as the rising levels of estrogen in peripuberty, which cause growth spurts at low levels and then the fusion of epiphyses at higher levels--and the hormonal variations during the menstrual cycle and their relation to genital phenotypic changes and intercurrent disease evolution. We turn next to adaptive changes in gonadal and other functions during aging, exercise, stress, starvation, and chronic diseases, which can serve as models for the effects of exogenous, hormonally active compounds. Then we review the states of borderline hormonal imbalances such as subclinical (having few or very mild symptoms, if any) hypothyroidism or hyperthyroidism, glucose intolerance, and other endocrine conditions. Finally, we review the deleterious systemic effects of gonadal imbalance. Information stemming from clinical observations leads to the concept of "no threshold" within the endocrine system and thus illustrates the importance of considering low-dose testing for chemicals that interfere with hormonal activity. We also urge attention to more sensitive, less visible end points such as osteoporosis, increased risk for cardiovascular disease, or cognitive changes. PMID:11250802

  15. Phase I/II Study of Sorafenib in Combination with Hepatic Arterial Infusion Chemotherapy Using Low-Dose Cisplatin and 5-Fluorouracil

    PubMed Central

    Ueshima, Kazuomi; Kudo, Masatoshi; Tanaka, Masatoshi; Kumada, Takashi; Chung, Hobyung; Hagiwara, Satoru; Inoue, Tatsuo; Yada, Norihisa; Kitai, Satoshi

    2015-01-01

    We conducted a phase I/II study in patients with advanced hepatocellular carcinoma (HCC) to determine the recommended dose, as well as the safety and efficacy, of combination therapy of sorafenib with hepatic arterial infusion chemotherapy (HAIC) using low dose cisplatin (CDDP) and 5-fluorouracil (5FU). Cohorts consisting of 3-6 patients with HCC received an escalated dose of CDDP and 5-FU until a maximum-tolerated dose was achieved. The treatment regimen was as follows: oral administration of sorafenib (400 mg twice daily for 28 days) combined with HAIC using CDDP (14-20 mg/m2, on days 1 and 8) and 5-FU (170-330 mg/m2, continuously on days 1-5 and 8-12) via an implanted catheter system). Each treatment cycle consisted of 28 days and three cycles of combination therapy. At the end of the first cycle, adverse events were evaluated and future dose escalation was determined. Eighteen patients with advanced HCC were enrolled. Dose-limiting toxicity was observed in two patients from cohort 1 (erythema multiforme and grade 4 thrombocytopenia) and in one patient from cohort 2 (erythema multiforme). Seven of the 18 patients achieved a partial response, seven showed stable disease, two were diagnosed as progressive disease, and two were not assessable. The response rate was 38.9% and the disease control rate was 77.8%. The time-to-progression was 9.7 months and the 1-year survival rate was 88.2%. Oral administration of 400 mg of sorafenib twice daily, 20 mg/m2 of intra-arterial infusion of CDDP, and 5-FU at 330 mg/m2 are the recommended doses for combination therapy, which was well tolerated and efficacious. This combination therapy may be a promising treatment for patients with advanced HCC. A large prospective randomized multicenter study (ClinicalTrials.gov Identifier NCT01214343) is ongoing. PMID:26734580

  16. LINE-1 Methylation Status Correlates Significantly to Post-Therapeutic Recurrence in Stage III Colon Cancer Patients Receiving FOLFOX-4 Adjuvant Chemotherapy

    PubMed Central

    Fan, Yun-Ching; Chang, Wei-Chiao; Lu, Chien-Yu; Wu, I-Chen; Hsu, Wen-Hung; Huang, Ching-Wen; Wang, Jaw-Yuan

    2015-01-01

    .57, p=0.041) Conclusion There was a significantly greater risk of early postoperative recurrence and a shorter period of disease-free survival in Stage III colon cancer patients exhibiting LINE-1 hypomethylation status after being treated with radical resection and FOLFOX chemotherapy. PMID:25919688

  17. Intensified High-Dose Chemoradiotherapy With Induction Chemotherapy in Patients With Locally Advanced Non-Small-Cell Lung Cancer-Safety and Toxicity Results Within a Prospective Trial

    SciTech Connect

    Poettgen, Christoph; Eberhardt, Wilfried E.; Gauler, Thomas; Krbek, Thomas; Berkovic, Katharina; Abu Jawad, Jehad; Korfee, Soenke; Teschler, Helmut; Stamatis, Georgios; Stuschke, Martin

    2010-03-01

    Purpose: To analyze the toxicity profile of an intensified definitive chemoradiotherapy (CRT) schedule in patients with locally advanced non-small-cell lung cancer (Stage IIIA N2/selected IIIB) treated within a prospective multicenter trial. Patients and Methods: After mediastinoscopy and routine staging procedures, three cycles of induction chemotherapy (cisplatin 50 mg/m{sup 2}, Days 1 and 8; paclitaxel 175 mg/m{sup 2} Day 1, every 21 days) were planned, followed by concurrent CRT (accelerated-hyperfractionated regimen, 45 Gy, 2 x 1.5 Gy/d, cisplatin 50 mg/m{sup 2}, Days 64 and 71, vinorelbine 20 mg/m{sup 2}, Days 64 and 71). At 45 Gy, a multidisciplinary panel decision was made regarding operability. Inoperable patients received definitive radiotherapy (total dose 65 or 71 Gy, depending on the mean lung dose) with additional concurrent chemotherapy (cisplatin 40 mg/m{sup 2}, Day 85; vinorelbine 15 mg/m{sup 2}, Days 85 and 92). Results: A total of 28 patients (23 men and 5 women; median age, 58 years; range 41-73; Stage IIIA in 3 and Stage IIIB in 25) were judged ineligible for surgery by the multidisciplinary panel and underwent definitive CRT (75% of the patients received 71 Gy). The maximum toxicity (Grade 3 or greater) during induction chemotherapy included leukopenia (11%) and anemia (4%). During concurrent CRT, leukopenia (Grade 3 or greater) was observed in 39% of the patients. The maximal nonhematologic toxicity during concurrent CRT included esophagitis (Grade 3 or greater) in 18% and pneumonitis (Grade 3 or greater) in 4% of the patients. At 3 years, the locoregional control rate was 52% (95% confidence interval, 29-75%) and the overall survival rate was 31% (95% confidence interval, 12-50%). Conclusion: This intensified treatment protocol with induction chemotherapy and concurrent CRT, including hyperfractionated-accelerated RT, showed only moderate toxicity and proved feasible. This treatment represents the definitive CRT arm of our ongoing

  18. [Chronic irradiation with low doses can be characterized by significant biological efficacy].

    PubMed

    Sorochyns'kyĭ, B V; Kripka, H V; Kuchma, O M

    2004-01-01

    Chromosomal aberrations (ChA) level was analyzed in the onion root meristem after the chronic irradiation with different dose capacities. It was shown that after the chronic irradiation with doses of 0.87 cGy, 2.61 cGy and 4.35 cGy the level of chromosomal aberrations depended on the dose capacity. Its value may also correspond to those which have been induced with accute irradiation. Biological efficacy of chronic irradiation may be from 20 to 1000 time folder in order to compare it with accute irradiation and this value depends on the irradiation regime. PMID:15882027

  19. Paclitaxel and Trastuzumab as Maintenance Therapy in Patients with HER2-Positive Metastatic Breast Cancer Who Underwent High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation.

    PubMed

    Cheng, Yee Chung; Rondón, Gabriela; Anderlini, Paolo; Khouri, Issa F; Champlin, Richard E; Ueno, Naoto T

    2013-01-01

    We examined the feasibility and safety of using paclitaxel and trastuzumab as maintenance therapy after high-dose chemotherapy (HDC) with autologous hematopoietic stem cell transplantation (AHST) for patients with HER2-positive metastatic breast cancer. Ten patients (9 women and 1 man) were enrolled in the study. The median age was 46.5 years (range, 27-65 years). The median follow-up time was 1003 days (range, 216-2526 days). All patients had metastatic disease, but 2 had only bone metastasis. One patient had complete response, 6 had partial response and 3 had stable disease to the standard-dose chemotherapy prior to transplantation. The conditioning regimen consisted of cyclophosphamide, carmustine, and thiotepa. After AHST, patients received weekly paclitaxel for 12 doses and trastuzumab every 3 weeks for 1 year as maintenance therapy. All patients experienced successful engraftment. The only grade 4 toxic effects observed were leukopenia and thrombocytopenia. The most common grade 3 toxic effect was neutropenic fever. No treatment-related deaths were observed. The median progression-free survival time was 441 days, and the median overall survival time was 955 days. Two patients died in accidents while their disease remained in remission. Five patients died with disease progression. At the time of this report, 3 patients are alive with stable disease, 1 of whom has remained free of disease progression for 2526 days since transplantation. Our findings indicate that paclitaxel plus trastuzumab as maintenance therapy after HDC with AHST for patients with HER2-positive metastatic breast cancer not only is feasible and safe but also results in survival outcomes similar to historical results. PMID:24155780

  20. Rituximab as consolidation therapy did not improve outcome in patients with diffuse large B-cell lymphoma at complete response after dose-dense chemotherapy (CHOP-14).

    PubMed

    Avilès, Agustin; Nambo, Maria-Jesùs; Huerta-Guzmàn, Judith; Silva, Luis; Neri, Natividad

    2015-04-01

    The authors started a clinical trial to assess the efficacy and toxicity of rituximab (R) as consolidation in patients with diffuse large B-cell lymphoma, with poor prognostic factors, who were in complete response (CR) after dose-dense chemotherapy (CHOP-14). Four hundred sixty-five untreated patients, with advanced stages (III and IV), older (median age >60 years old), and high clinical risk, were treated with dose-dense CHOP-14 (cyclophosphamide 1500 mg/m(2), i.v., day 1; vincristine 2 mg, i.v., standard dose, day 1; epirubicin 120 mg/m(2), i.v., day 1; and prednisone 60 mg/m(2), p.o., days 1-5) every 14 days for six cycles. If CR was achieved, the patients were allocated to receive R (375 mg/m(2), days 1, 8, 15, and 22) at 3 and 9 months after chemotherapy. Three hundred twenty-five patients achieved CR (70%) and were allocated to receive R (151 patients) or not (174 patients). Actuarial curves at 5 years showed that progression-free survival (PFS) was 51% (95% confidence interval [CI]: 44%-58%) in the R group and 53% (95% CI: 47%-59%) in the observation group (p=0.8). Overall survival (OS) was 65% (95% CI: 58%-71%) and 66% (95% CI: 59%-72%), respectively (p=0.78). Late toxicities were more frequent in the R group. The authors showed that the use of R as a consolidation treatment was not useful to improve PFS and OS and toxicity secondary to R was frequent. They did not recommend the use of R as consolidation in this patient setting. PMID:25871407

  1. Rituximab-CHOP-ESHAP vs CHOP-ESHAP-high-dose therapy vs conventional CHOP chemotherapy in high-intermediate and high-risk aggressive non-Hodgkin's lymphoma.

    PubMed

    Intragumtornchai, Tanin; Bunworasate, Udomsak; Nakorn, Thanyaphong Na; Rojnuckarin, Ponlapat

    2006-07-01

    With currently available combination chemotherapy regimens, the outcome of the patients newly diagnosed with aggressive non-Hodgkin's lymphoma (NHL) identified as 'high' and 'high-intermediate' risk groups according to the international prognostic index (IPI) is still unsatisfactory and a more innovative therapy is urgently required to improve the survival of the patients. The purpose of this study was to compare the efficacy of rituximab given in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and ESHAP (etoposide, methylprednisolone, high-dose Ara-C, cisplatin) vs CHOP-ESHAP and upfront high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) vs standard CHOP in patients aged < or = 65 years old newly diagnosed with 'high' and 'high-intermediate' risk aggressive lymphoma enrolled onto two consecutive treatment trials at the institute. Between May 1995 - July 2002, 84 patients, aged 15 - 65 years old, with newly diagnosed aggressive NHL and an age-adjusted IPI of 2 or 3 were enrolled. The median age of the patients was 38 years (range 15 - 65). The baseline demographic features, in particular the major prognostic variables, were similar between the treatment groups. Patients treated with rituximab-CHOP-ESHAP received eight cycles of rituximab (375 mg m(-2) on day 1 of cycles 1 - 6 and days 21 and 28 of cycle 7) plus CHOP (day 3 of cycles 1, 3 and 5) and ESHAP (day 3 of cycles 2, 4 and 6 and day 1 of cycle 7) at 21-day intervals. Patients enrolled onto the CHOP-ESHAP-HDT arm (n = 23) were treated with three courses of CHOP and then switched to two or four cycles of ESHAP followed by HDT. Patients treated with CHOP alone (n = 25) were treated with the standard eight cycles of CHOP. The rate of complete remission was significantly improved with rituximab-CHOP-ESHAP compared with either CHOP-ESHAP-HDT or CHOP alone (67% compared with 44% and 36%, respectively; p = 0.043). With a median follow-up time of 53 months, the 5

  2. The effects of gemcitabine and capecitabine combination chemotherapy and of low-dose adjuvant GM-CSF on the levels of myeloid-derived suppressor cells in patients with advanced pancreatic cancer.

    PubMed

    Annels, Nicola E; Shaw, Victoria E; Gabitass, Rachel F; Billingham, Lucinda; Corrie, Pippa; Eatock, Martin; Valle, Juan; Smith, David; Wadsley, Jonathan; Cunningham, David; Pandha, Hardev; Neoptolemos, John P; Middleton, Gary

    2014-02-01

    In pre-clinical models, the only two chemotherapy drugs which have been demonstrated to directly reduce the number of myeloid-derived suppressor cells (MDSCs) are gemcitabine and 5-fluorouracil. Here we analyze the dynamics of MDSCs, phenotyped as Lin-DR-CD11b+, in patients with advanced pancreatic cancer receiving the combination of gemcitabine and capecitabine, a 5-FU pro-drug. We found no evidence that gemcitabine and capecitabine directly reduce MDSC% in patients. Gemcitabine and capecitabine reduced MDSCs in 42% of patients (n = 19) and MDSC% fell in only 3/9 patients with above-median baseline MDSCs. In 5/8 patients with minimal tumour volume change on treatment, the MDSC% went up: increases in MDSC% in these patients appeared to correlate with sustained cancer-related inflammatory cytokine upregulation. In a separate cohort of 21 patients treated with gemcitabine and capecitabine together with concurrently administered GV1001 vaccine with adjuvant GM-CSF, the MDSC% fell in 18/21 patients and there was a significant difference in the trajectory of MDSCs between those receiving GV1001 and GM-CSF in combination with chemotherapy and those receiving chemotherapy alone. Thus, there was no evidence that the addition of low-dose adjuvant GM-CSF increased Lin-DR-CD11b+ MDSC in patients receiving combination chemoimmunotherapy. 9/21 patients developed an immune response to GV1001 and the MDSCs fell in 8 of these 9 patients, 6 of whom had above-median pre-vaccination MDSC levels. A high pre-vaccination MDSC% does not preclude the development of immunity to a tumour-associated antigen. PMID:24292263

  3. Outcome analysis of high-dose chemotherapy and autologous stem cell transplantation in adolescent and young adults with relapsed or refractory Hodgkin lymphoma.

    PubMed

    Akhtar, Saad; Rauf, Shahzad M; Elhassan, Tusneem A M; Maghfoor, Irfan

    2016-09-01

    High-dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT) can salvage many patients with relapsed or refractory Hodgkin's lymphoma (HL). We are reporting the outcome of HDC auto-SCT and the impact of 21 prognostic factors in relapsed and refractory adolescent (14-21 years) and young adult (>21-30 years) (AYA) HL patients. We used Fine and Gray's competing risk analysis method and regression model for outcome analysis. From 1996 to 2013, 290 consecutive patients with biopsy-proven HL underwent HDC auto-SCT for relapsed/refractory HL; 216 patients (74.5 %) were AYA at the time of auto-SCT. Male/female were equal, median age at auto-SCT was 22.4 years, and there were 94 adolescent (43.5 %) and 122 young adults (56.5 %). There was refractory disease in 121 (56 %) patients, relapsed in 95 (44 %). Median follow-up was 72.6 months. The Kaplan-Meier method estimated that 5-year overall survival is 62.7 % (adolescents (63.5 %), young adults (62 %)) and event-free survival was 51.3 %. Five-year cumulative incidence of disease-specific death (DS-death) is 33 % and that of DS-event is 45 %. For DS-death, the multivariate analysis identified complete remission (CR) duration of <12 months (hazard ratio (HR) 3.61, P = 0.0009), no CR after salvage (HR: 3.93, P = 0.0002), and nodular sclerosis pathology (HR 3.3, P = 0.016) and positive B symptoms (HR 2, P = 0.028) as negative factors. For DS-event, CR duration of <12 months (HR 1.88, P = 0.02), no CR after salvage (HR 3.47, P = 0.000005) and nodular sclerosis pathology (HR 1.88, P = 0.02) were found significant. The Kaplan-Meier method estimated overall survival (OS) at 36 months with 0-2:3:4 factors being 93.6:54:21 %, respectively (P value <0.001). Kaplan-Meier estimated event-free survival (EFS) at 36 months with 0-1:2:3 factors being 84.6:65:31 %, respectively (P value <0.001). Clinically, adolescents have similar outcomes as young adults. PMID:27376363

  4. Treatment of aggressive multiple myeloma by high-dose chemotherapy and total body irradiation followed by blood stem cells autologous graft

    SciTech Connect

    Fermand, J.P.; Levy, Y.; Gerota, J.; Benbunan, M.; Cosset, J.M.; Castaigne, S.; Seligmann, M.; Brouet, J.C.

    1989-01-01

    Eight patients with stage III aggressive multiple myeloma, refractory to current chemotherapy in six cases, were treated by high-dose chemotherapy (nitrosourea, etoposide, and melphalan) (HDC) and total body irradiation (TBI), followed by autografting with blood stem cells. These cells were previously collected by leukapheresis performed during hematologic recovery following cytotoxic drug-induced bone marrow aplasia. Seven patients were alive 9 to 17 months after HDC-TBI and graft. One died at day 40 from cerebral bleeding. All living patients achieved a 90% or greater reduction in tumor mass. In two cases, a complete remission (CR) has persisted at a follow-up of 15 and 16 months. Three patients have been well and off therapy with stable minimal residual disease (RD) since 10, 11, and 17 months, respectively. A patient in apparent CR and another with RD have relapsed 9 to 12 months posttreatment. Autologous blood-derived hematopoietic stem cells induced successful and sustained engraftment in all living patients. These results, although still preliminary, indicate that HDC and TBI, followed by blood stem cells autograft, which has both practical and theoretical interest over allogeneic or autologous bone marrow transplantation, deserve consideration in selected patients with multiple myeloma.

  5. Significance of PIK3CA Mutations in Patients with Early Breast Cancer Treated with Adjuvant Chemotherapy: A Hellenic Cooperative Oncology Group (HeCOG) Study

    PubMed Central

    Alexopoulou, Zoi; Kalogeras, Konstantine T.; Zagouri, Flora; Timotheadou, Eleni; Gogas, Helen; Pentheroudakis, George; Christodoulou, Christos; Koutras, Angelos; Bafaloukos, Dimitrios; Aravantinos, Gerasimos; Papakostas, Pavlos; Charalambous, Elpida; Papadopoulou, Kyriaki; Varthalitis, Ioannis; Efstratiou, Ioannis; Zaramboukas, Thomas; Patsea, Helen; Scopa, Chrisoula D.; Skondra, Maria; Kosmidis, Paris; Pectasides, Dimitrios; Fountzilas, George

    2015-01-01

    Background The PI3K-AKT pathway is frequently activated in breast cancer. PIK3CA mutations are most frequently found in the helical (exon 9) and kinase (exon 20) domains of this protein. The aim of the present study was to examine the role of different types of PIK3CA mutations in combination with molecular biomarkers related to PI3K-AKT signaling in patients with early breast cancer. Methods Tumor tissue samples from 1008 early breast cancer patients treated with adjuvant chemotherapy in two similar randomized trials of HeCOG were examined. Tumors were subtyped with immunohistochemistry (IHC) and FISH for ER, PgR, Ki67, HER2 and androgen receptor (AR). PIK3CA mutations were analyzed by Sanger sequencing (exon 20) and qPCR (exon 9) (Sanger/qPCR mutations). In 610 cases, next generation sequencing (NGS) PIK3CA mutation data were also available. PIK3CA mutations and PTEN protein expression (IHC) were analyzed in luminal tumors (ER and/or PgR positive), molecular apocrine carcinomas (MAC; ER/PgR negative / AR positive) and hormone receptor (ER/PgR/AR) negative tumors. Results PIK3CA mutations were detected in 235/1008 tumors (23%) with Sanger/qPCR and in 149/610 tumors (24%) with NGS. Concordance between the two methods was good with a Kappa coefficient of 0.76 (95% CI 0.69–0.82). Lobular histology, low tumor grade and luminal A tumors were associated with helical domain mutations (PIK3CAhel), while luminal B with kinase domain mutations (PIK3CAkin). The overall incidence of PIK3CA mutations was higher in luminal as compared to MAC and hormone receptor negative tumors (p = 0.004). Disease-free and overall survival did not significantly differ with respect to PIK3CA mutation presence and type. However, a statistically significant interaction between PIK3CA mutation status and PTEN low protein expression with regard to prognosis was identified. Conclusions The present study did not show any prognostic significance of specific PIK3CA mutations in a large group of

  6. A Contralateral Esophagus-Sparing Technique to Limit Severe Esophagitis Associated With Concurrent High-Dose Radiation and Chemotherapy in Patients With Thoracic Malignancies

    SciTech Connect

    Al-Halabi, Hani; Paetzold, Peter; Sharp, Gregory C.; Olsen, Christine; Willers, Henning

    2015-07-15

    Purpose: Severe (Radiation Therapy Oncology Group [RTOG] grade 3 or greater) esophagitis generally occurs in 15% to 25% of non–small cell lung cancer (NSCLC) patients undergoing concurrent chemotherapy and radiation therapy (CCRT), which may result in treatment breaks that compromise local tumor control and pose a barrier to dose escalation. Here, we report a novel contralateral esophagus-sparing technique (CEST) that uses intensity modulated radiation therapy (IMRT) to reduce the incidence of severe esophagitis. Methods and Materials: We reviewed consecutive patients with thoracic malignancies undergoing curative CCRT in whom CEST was used. The esophageal wall contralateral (CE) to the tumor was contoured as an avoidance structure, and IMRT was used to guide a rapid dose falloff gradient beyond the target volume in close proximity to the esophagus. Esophagitis was recorded based on the RTOG acute toxicity grading system. Results: We identified 20 consecutive patients treated with CCRT of at least 63 Gy in whom there was gross tumor within 1 cm of the esophagus. The median radiation dose was 70.2 Gy (range, 63-72.15 Gy). In all patients, ≥99% of the planning and internal target volumes was covered by ≥90% and 100% of prescription dose, respectively. Strikingly, no patient experienced grade ≥3 esophagitis (95% confidence limits, 0%-16%) despite the high total doses delivered. The median maximum dose, V45, and V55 of the CE were 60.7 Gy, 2.1 cc, and 0.4 cc, respectively, indicating effective esophagus cross-section sparing by CEST. Conclusion: We report a simple yet effective method to avoid exposing the entire esophagus cross-section to high doses. By using proposed CE dose constraints of V45 <2.5 cc and V55 <0.5 cc, CEST may improve the esophagus toxicity profile in thoracic cancer patients receiving CCRT even at doses above the standard 60- to 63-Gy levels. Prospective testing of CEST is warranted.

  7. Hyperthermic intraperitoneal chemotherapy: Rationale and technique

    PubMed Central

    González-Moreno, Santiago; González-Bayón, Luis A; Ortega-Pérez, Gloria

    2010-01-01

    The combination of complete cytoreductive surgery and perioperative intraperitoneal chemotherapy provides the only chance for long-term survival for selected patients diagnosed with a variety of peritoneal neoplasms, either primary or secondary to digestive or gynecologic malignancy. Hyperthermic intraperitoneal chemotherapy (HIPEC) delivered in the operating room once the cytoreductive surgical procedure is finalized, constitutes the most common form of administration of perioperative intraperitoneal chemotherapy. This may be complemented in some instances with early postoperative intraperitoneal chemotherapy (EPIC). HIPEC combines the pharmacokinetic advantage inherent to the intracavitary delivery of certain cytotoxic drugs, which results in regional dose intensification, with the direct cytotoxic effect of hyperthermia. Hyperthermia exhibits a selective cell-killing effect in malignant cells by itself, potentiates the cytotoxic effect of certain chemotherapy agents and enhances the tissue penetration of the administered drug. The chemotherapeutic agents employed in HIPEC need to have a cell cycle nonspecific mechanism of action and should ideally show a heat-synergistic cytotoxic effect. Delivery of HIPEC requires an apparatus that heats and circulates the chemotherapeutic solution so that a stable temperature is maintained in the peritoneal cavity during the procedure. An open abdomen (Coliseum) or closed abdomen technique may be used, with no significant differences in efficacy proven to date. Specific technical training and a solid knowledge of regional chemotherapy management are required. Concerns about safety of the procedure for operating room personnel are expected but are manageable if universal precautions and standard chemotherapy handling procedures are used. Different HIPEC drug regimens and dosages are currently in use. A tendency for concurrent intravenous chemotherapy administration (bidirectional chemotherapy, so-called “HIPEC plus”) has

  8. Defining the dose of gemtuzumab ozogamicin in combination with induction chemotherapy in acute myeloid leukemia: a comparison of 3 mg/m2 with 6 mg/m2 in the NCRI AML17 Trial.

    PubMed

    Burnett, Alan; Cavenagh, Jamie; Russell, Nigel; Hills, Robert; Kell, Jonathan; Jones, Gail; Nielsen, Ove Juul; Khwaja, Asim; Thomas, Ian; Clark, Richard

    2016-06-01

    Arecent source data meta-analysis of randomized trials in adults assessing the immunoconjugate gemtuzumab ozogamicin combined with standard chemotherapy in acute myeloid leukemia showed a significant survival benefit in patients without an adverse karyotype. It is not clear whether the optimal dose should be 3 mg/m(2) or 6 mg/m(2) In this study, we randomized 788 patients to a single dose of gemtuzumab ozogamicin 3 mg/m(2) or 6 mg/m(2) with the first course of induction therapy. We found that the rate of complete remission was higher with 3 mg/m(2) [82% vs 76%; odds ratio 1.46 (1.04-2.06); P=0.03], but this was balanced by a higher rate of complete remission with incomplete peripheral blood count recovery in the 6 mg/m(2) treatment (10% vs 7%) resulting in similar overall response rate [89% vs 86%; hazard ratio 1.34 (0.88-2.04); P=0.17]. There was no overall difference in relapse or survival at four years between the arms: 46% vs 54%; hazard ratio 1.17 (0.94-1.45), P=0.5, and 50% versus 47%; hazard ratio 1.10 (0.90-1.34), P=0.3, respectively. The 30- and 60-day mortality was significantly higher in the 6 mg/m(2) recipients: 7% versus 3%; hazard ratio 2.07 (1.11-3.87), P=0.02, and 9% versus 5%; hazard ratio 1.99 (1.17-3.39), P=0.01, respectively, which in addition was associated with a higher rate of veno-occlusive disease (5.6% vs 0.5%; P<0.0001). Our conclusion from this trial is that there is no advantage in using a single dose of 6 mg/m(2) of gemtuzumab ozogamicin in combination with induction chemotherapy when compared with a 3 mg/m(2) dose, with respect to response, disease-free and overall survival, either overall, or in any disease subgroup. (AML17 was registered as ISRCTN55675535). PMID:26921360

  9. Combination therapy of anti-cancer bioactive peptide with Cisplatin decreases chemotherapy dosing and toxicity to improve the quality of life in xenograft nude mice bearing human gastric cancer

    PubMed Central

    2014-01-01

    Background A great challenge of cancer chemotherapy is to eliminate cancer cells and concurrently maintain the quality of life (QOL) for cancer patients. Previously, we identified a novel anti-cancer bioactive peptide (ACBP), a peptide induced in goat spleen or liver following immunization with human gastric cancer protein extract. ACBP alone exhibited anti-tumor activity without measurable side effects. Thus, we hypothesize that ACBP and combined chemotherapy could improve the efficacy of treatment and lead to a better QOL. Results In this study, ACBP was isolated and purified from immunized goat liver, and designated as ACBP-L. The anti-tumor activity was investigated in a previously untested human gastric cancer MGC-803 cell line and tumor model. ACBP-L inhibited cell proliferation in vitro in a dose and time dependent manner, titrated by MTT assay. The effect of ACBP-L on cell morphology was observed through light and scanning electron microscopy. In vivo ACBP-L alone significantly inhibited MGC-803 tumor growth in a xenograft nude mouse model without measurable side effects. Treatment with the full dosage of Cisplatin alone (5 mg/kg every 5 days) strongly suppressed tumor growth. However, the QOL in these mice had been significantly affected when measured by food intakes and body weight. The combinatory regiment of ACBP-L with a fewer doses of Cisplatin (5 mg/kg every 10 days) resulted in a similar anti-tumor activity with improved QOL. 18F-FDG PET/CT scan was used to examine the biological activity in tumors of live animals and indicated the consistent treatment effects. The tumor tissues were harvested after treatment, and ACBP-L and Cisplatin treatment suppressed Bcl-2, and induced Bax, Caspase 3, and Caspase 8 molecules as detected by RT-PCR and immunohistochemistry. The combinatory regiment induced stronger Bax and Caspase 8 protein expression. Conclusion Our current finding in this gastric cancer xenograft animal model demonstrated that ACBP-L could

  10. Defining the dose of gemtuzumab ozogamicin in combination with induction chemotherapy in acute myeloid leukemia: a comparison of 3 mg/m2 with 6 mg/m2 in the NCRI AML17 Trial

    PubMed Central

    Burnett, Alan; Cavenagh, Jamie; Russell, Nigel; Hills, Robert; Kell, Jonathan; Jones, Gail; Nielsen, Ove Juul; Khwaja, Asim; Thomas, Ian; Clark, Richard

    2016-01-01

    Arecent source data meta-analysis of randomized trials in adults assessing the immunoconjugate gemtuzumab ozogamicin combined with standard chemotherapy in acute myeloid leukemia showed a significant survival benefit in patients without an adverse karyotype. It is not clear whether the optimal dose should be 3 mg/m2 or 6 mg/m2. In this study, we randomized 788 patients to a single dose of gemtuzumab ozogamicin 3 mg/m2 or 6 mg/m2 with the first course of induction therapy. We found that the rate of complete remission was higher with 3 mg/m2 [82% vs. 76%; odds ratio 1.46 (1.04–2.06); P=0.03], but this was balanced by a higher rate of complete remission with incomplete peripheral blood count recovery in the 6 mg/m2 treatment (10% vs. 7%) resulting in similar overall response rate [89% vs. 86%; hazard ratio 1.34 (0.88–2.04); P=0.17]. There was no overall difference in relapse or survival at four years between the arms: 46% vs. 54%; hazard ratio 1.17 (0.94–1.45), P=0.5, and 50% versus 47%; hazard ratio 1.10 (0.90–1.34), P=0.3, respectively. The 30- and 60-day mortality was significantly higher in the 6 mg/m2 recipients: 7% versus 3%; hazard ratio 2.07 (1.11–3.87), P=0.02, and 9% versus 5%; hazard ratio 1.99 (1.17–3.39), P=0.01, respectively, which in addition was associated with a higher rate of veno-occlusive disease (5.6% vs. 0.5%; P<0.0001). Our conclusion from this trial is that there is no advantage in using a single dose of 6 mg/m2 of gemtuzumab ozogamicin in combination with induction chemotherapy when compared with a 3 mg/m2 dose, with respect to response, disease-free and overall survival, either overall, or in any disease subgroup. (AML17 was registered as ISRCTN55675535.) PMID:26921360

  11. Mobilization of peripheral blood stem cells with chemotherapy and recombinant human granulocyte colony-stimulating factor (rhG-CSF): a randomized evaluation of different doses of rhG-CSF.

    PubMed

    Demirer, T; Ayli, M; Ozcan, M; Gunel, N; Haznedar, R; Dagli, M; Fen, T; Genc, Y; Dincer, S; Arslan, O; Gürman, G; Demirer, S; Ozet, G; Uysal, A; Konuk, N; Ilhan, O; Koc, H; Akan, H

    2002-02-01

    To date, no randomized study has compared different doses of recombinant human granulocyte colony-stimulating factor (rhG-CSF) following submyeloablative mobilization chemotherapy. Therefore, we evaluated the effect of different doses of rhG-CSF following mobilization chemotherapy on yields of CD34+ peripheral blood stem cells (PBSC). Fifty patients were randomized to receive 8 (n = 25) versus 16 microg/kg/d (n = 25) of rhG-CSF following mobilization chemotherapy. The median number of CD34+ cells collected after 8 microg/kg/d of rhG-CSF was 2.36 x 10(6)/kg (range, 0.21-7.80), compared with 7.99 (2.76-14.89) after 16 microg/kg/d (P < 0.001). Twenty out of 25 (80%) patients in the low-dose and 23 out of 25 (92%) in the high-dose rhG-CSF arm underwent high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT). Median days to white blood cell engraftment in patients mobilized with 8 microg/kg and 16 microg/kg of rhG-CSF were 12 (10-20) and 9 (8-11) respectively (P < 0.001). There was no difference between the two groups regarding the other parameters of peritransplant morbidity: days to platelet engraftment (P = 0.10), number of red blood cell (P = 0.56) and platelet transfusions (P = 0.22), days of total parenteral nutrition requirement (P = 0.84), fever (P = 0.93) and antibiotics (P = 0.77), and number of different antibiotics used (P = 0.58). These data showed that higher doses of rhG-CSF following submyeloablative mobilization chemotherapy were associated with a clear dose-response effect based on the collected cell yields. Based on the parameters of peritransplant morbidity, 8 microg/kg/d was as effective as 16 microg/kg/d except for a rapid neutrophil engraftment in the high-dose arm. Therefore, in routine clinical practice, despite some advantage in the use of higher doses of rhG-CSF, lower doses may be used for PBSC collections following chemotherapy-based mobilization regimens in this cost-conscious era. PMID:11841454

  12. Optimizing initial chemotherapy for metastatic pancreatic cancer.

    PubMed

    Mantripragada, Kalyan C; Safran, Howard

    2016-05-01

    The two combination chemotherapy regimens FOLFIRINOX and gemcitabine plus nab-paclitaxel represent major breakthroughs in the management of metastatic pancreatic cancer. Both regimens showed unprecedented survival advantage in the setting of front-line therapy. However, their application for treatment of patients in the community is challenging because of significant toxicities, thus limiting potential benefits to a narrow population of patients. Modifications to the dose intensity or schedule of those regimens improve their tolerability, while likely retaining survival advantage over single-agent chemotherapy. Newer strategies to optimize these two active regimens in advanced pancreatic cancer are being explored that can help personalize treatment to individual patients. PMID:26939741

  13. Cancer Chemotherapy

    MedlinePlus

    ... controlled way. Cancer cells keep growing without control. Chemotherapy is drug therapy for cancer. It works by killing the cancer ... It depends on the type and amount of chemotherapy you get and how your body reacts. Some ...

  14. Cancer Chemotherapy

    MedlinePlus

    ... cells grow and die in a controlled way. Cancer cells keep forming without control. Chemotherapy is drug ... Your course of therapy will depend on the cancer type, the chemotherapy drugs used, the treatment goal ...

  15. Management of Mucositis During Chemotherapy: From Pathophysiology to Pragmatic Therapeutics.

    PubMed

    Van Sebille, Ysabella Z A; Stansborough, Romany; Wardill, Hannah R; Bateman, Emma; Gibson, Rachel J; Keefe, Dorothy M

    2015-11-01

    Chemotherapy-induced mucositis is a common condition caused by the breakdown of the mucosal barrier. Symptoms can include pain, vomiting and diarrhoea, which can often necessitate chemotherapy treatment breaks or dose reductions, thus compromising survival outcomes. Despite the significant impact of mucositis, there are currently limited clinically effective pharmacological therapies for the pathology. New emerging areas of research have been proposed to play key roles in the development of mucositis, providing rationale for potential new therapeutics for the prevention, treatment or management of chemotherapy-induced mucositis. This review aims to address these new areas of research and to comment on the therapeutics arising from them. PMID:26384312

  16. The Potential for Bayesian Compressive Sensing to Significantly Reduce Electron Dose in High Resolution STEM Images

    SciTech Connect

    Stevens, Andrew J.; Yang, Hao; Carin, Lawrence; Arslan, Ilke; Browning, Nigel D.

    2014-02-11

    The use of high resolution imaging methods in the scanning transmission electron microscope (STEM) is limited in many cases by the sensitivity of the sample to the beam and the onset of electron beam damage (for example in the study of organic systems, in tomography and during in-situ experiments). To demonstrate that alternative strategies for image acquisition can help alleviate this beam damage issue, here we apply compressive sensing via Bayesian dictionary learning to high resolution STEM images. These experiments successively reduce the number of pixels in the image (thereby reducing the overall dose while maintaining the high resolution information) and show promising results for reconstructing images from this reduced set of randomly collected measurements. We show that this approach is valid for both atomic resolution images and nanometer resolution studies, such as those that might be used in tomography datasets, by applying the method to images of strontium titanate and zeolites. As STEM images are acquired pixel by pixel while the beam is scanned over the surface of the sample, these post acquisition manipulations of the images can, in principle, be directly implemented as a low-dose acquisition method with no change in the electron optics or alignment of the microscope itself.

  17. High-dose chemotherapy and autologous stem cell support followed by post-transplant doxorubicin and taxol as initial therapy for metastatic breast cancer: hematopoietic tolerance and efficacy.

    PubMed

    deMagalhaes-Silverman, M; Hammert, L; Lembersky, B; Lister, J; Rybka, W; Ball, E

    1998-06-01

    A multistep HDC regimen was designed as first-line chemotherapy for MBC. Twenty-four patients with MBC and no previous chemotherapy for metastatic disease were treated with high-dose cyclophosphamide (5000 mg/m2), and etoposide (1000 mg/m2) (CyVP16), followed by granulocyte colony-stimulating factor (G-CSF). Peripheral blood stem cells (PBSCs) were collected. Subsequently patients received cyclophosphamide (6000 mg/m2), thiotepa (500 mg/m2) and carboplatin (800 mg/m2) (CTCb) with hematopoietic rescue. Upon recovery from hematopoietic and gastrointestinal toxicity three cycles of doxorubicin (50 mg/m2) and taxol (150 mg/m2) were delivered. After CyVP16 42% of patients developed neutropenic fevers. There was one documented episode of bacteremia. Patients received CTCb 32 days after starting CyVP16. After CTCb the median number of days to ANC >5 x 10(9)/l was 10 and to a platelet count >20 x 10(9)/l was 14. Neutropenic fevers developed in 16 patients. There were no hemorrhagic episodes. A total of 69 cycles of doxorubicin and taxol were delivered (87% of planned). The median time from PBSC infusion to the first cycle was 38 days. The median time to the second cycle was 27 days and to the last cycle was 24 days. One patient developed congestive heart failure. Two episodes of neutropenic fevers were observed. No toxicity-related deaths were observed. Grafts are stable at 6 months post transplantation. This multistep regimen is feasible with acceptable toxicity. PMID:9674853

  18. A Matter of Timing: Identifying Significant Multi-Dose Radiotherapy Improvements by Numerical Simulation and Genetic Algorithm Search

    PubMed Central

    Angus, Simon D.; Piotrowska, Monika Joanna

    2014-01-01

    Multi-dose radiotherapy protocols (fraction dose and timing) currently used in the clinic are the product of human selection based on habit, received wisdom, physician experience and intra-day patient timetabling. However, due to combinatorial considerations, the potential treatment protocol space for a given total dose or treatment length is enormous, even for relatively coarse search; well beyond the capacity of traditional in-vitro methods. In constrast, high fidelity numerical simulation of tumor development is well suited to the challenge. Building on our previous single-dose numerical simulation model of EMT6/Ro spheroids, a multi-dose irradiation response module is added and calibrated to the effective dose arising from 18 independent multi-dose treatment programs available in the experimental literature. With the developed model a constrained, non-linear, search for better performing cadidate protocols is conducted within the vicinity of two benchmarks by genetic algorithm (GA) techniques. After evaluating less than 0.01% of the potential benchmark protocol space, candidate protocols were identified by the GA which conferred an average of 9.4% (max benefit 16.5%) and 7.1% (13.3%) improvement (reduction) on tumour cell count compared to the two benchmarks, respectively. Noticing that a convergent phenomenon of the top performing protocols was their temporal synchronicity, a further series of numerical experiments was conducted with periodic time-gap protocols (10 h to 23 h), leading to the discovery that the performance of the GA search candidates could be replicated by 17–18 h periodic candidates. Further dynamic irradiation-response cell-phase analysis revealed that such periodicity cohered with latent EMT6/Ro cell-phase temporal patterning. Taken together, this study provides powerful evidence towards the hypothesis that even simple inter-fraction timing variations for a given fractional dose program may present a facile, and highly cost

  19. Chemotherapy and fertility.

    PubMed

    Blumenfeld, Zeev

    2012-06-01

    The overall increase in cancer prevalence and the significant increase in long-term survival have generated worldwide interest in preserving fertility in young women exposed to gonadotoxic chemo- and radiotherapy. Infertility represents one of the main long-term consequences of combination chemotherapy given for lymphoma, leukaemia and other malignancies in young women. The gonadotoxic effect of various chemotherapeutic agents is diverse, may involve a variety of pathophysiologic mechanisms, and is not unequivocally understood. Proliferating cells, such as in tissues with high turnover (i.e. bone marrow, gastrointestinal tract and growing ovarian follicles) are more vulnerable to the toxic effect of alkylating agents. These agents may also be cytotoxic to cells at rest, as they are not cell-cycle specific. Alkylating agents, the most gonadotoxic chemotherapeutic medications, cause dose-dependent, direct destruction of oocytes and follicular depletion, and may bring about cortical fibrosis and ovarian blood-vessel damage. The reported rate of premature ovarian failure after various diseases and chemotherapeutic protocols differ enormously, and depend mainly on the chemotherapeutic protocol used and age range of the woman. Several options have been proposed for preserving female fertility, despite gonadotoxic chemotherapy: ovarian transposition, cryopreservation of embryos, unfertilised metaphase-II oocytes and ovarian tissue, and administration of gonadotropin-releasing hormone agonistic analogs in an attempt to decrease the gonadotoxic effects of chemotherapy by simulating a prepubertal hormonal milieu. None of these methods is ideal and none guarantees future fertility in all survivors; therefore, a combination of methods is recommended for maximising women's chances of future fertility. PMID:22281514

  20. Prognostic significance of SUV on PET/CT in patients with localised oesophagogastric junction cancer receiving neoadjuvant chemotherapy/chemoradiation: a systematic review and meta-analysis

    PubMed Central

    Zhu, W; Xing, L; Yue, J; Sun, X; Sun, X; Zhao, H; Yu, J

    2012-01-01

    Objective The objective of this study was to comprehensively review the evidence for use of pre-treatment, post-treatment and changes in tumour glucose uptake that were assessed by 18-fludeoxyglucose (18F-FDG) positron emission tomography (PET) early, during or immediately after neoadjuvant chemotherapy/chemoradiation to predict prognosis of localised oesophagogastric junction (AEG) cancer. Methods We searched for articles published in English; limited to AEG; 18F-FDG uptake on PET performed on a dedicated device; dealt with the impact of standard uptake value (SUV) on survival. We extracted an estimate of the log hazard ratios (HRs) and their variances and performed meta-analysis. Results 798 patients with AEG were included. And the scan time for 18F-FDG-PET was as follows: prior to therapy (PET1, n=646), exactly 2 weeks after initiation of neoadjuvant therapy (PET2, n=245), and pre-operatively (PET3, n=278). In the two meta-analyses for overall survival, including the studies that dealt with reduction of tumour maximum SUV (SUVmax) (from PET1 to PET2/PET3 and from PET1 to PET2), the results were similar, with the overall HR for non-responders being 1.83 [95% confidence interval (CI), 1.41–2.36] and 2.62 (95% CI, 1.61–4.26), respectively; as for disease-free survival, the combined HR was 2.92 (95% CI, 2.08–4.10) and 2.39 (95% CI, 1.57–3.64), respectively. The meta-analyses did not attribute significant prognostic values to SUVmax before and during therapy in localised AEG. Conclusion Relative changes in FDG-uptake of AEG are better prognosticators. Early metabolic changes from PET1 to PET2 may provide the same accuracy for prediction of treatment outcome as late changes from PET1 to PET3. PMID:22337686

  1. Chemotherapy with or without low-dose interleukin-2 in advanced non-small cell lung cancer: results from a phase III randomized multicentric trial.

    PubMed

    Ridolfi, Laura; Bertetto, Oscar; Santo, Antonio; Naglieri, Emanuele; Lopez, Massimo; Recchia, Francesco; Lissoni, Paolo; Galliano, Marco; Testore, Franco; Porta, Camillo; Maglie, Monica; Dall'agata, Monia; Fumagalli, Luca; Ridolfi, Ruggero

    2011-10-01

    Non-small cell lung cancer (NSCLC) is associated with IL-2-dependent cell-mediated immunodeficiency. As IL-2 is the main lymphocyte growth factor, a phase III randomized multicenter trial was conducted to evaluate the impact of subcutaneous low-dose IL-2 added to standard chemotherapy (CT) on overall survival (OS) in advanced NSCLC patients. Patients (n=241) with histologically confirmed stage IIIb or IV non-operable NSCLC underwent stratified randomization on the basis of center, ECOG PS, stage of disease and percentage of weight loss. Patients received gemcitabine (1000 mg/m2) on days 1 and 8 + cisplatin (100 mg/m2) on day 2 every 21 days for a maximum of 6 cycles [chemotherapy (CT) arm]. In the CT+IL-2 arm, patients also received low-dose subcutaneous IL-2 3,000,000 IU/die on days 3-5, 9-11, 15-17. The study had 90% power to detect a 20% absolute increase in 1-year OS with 118 patients/arm. An overall response (OR) rate of 12.8% (14% in the CT+IL-2 arm and 11.4% in CT arm) was observed. Stable disease was 70 and 66.7%, and progressive disease 16 and 21.8% in the CT+IL-2 and CT arms, respectively. No differences in response were found in any subgroup analysis. At a median follow-up of 32 months, 1-year OS was 45% for the CT+IL-2 arm vs. 51% for the CT arm (p=0.456 log-rank). Median progression-free survival was 6.6 months in the CT+IL-2 arm vs. 6.9 months in the CT arm (p=0.573, log-rank). A higher number of grade 4 toxicities were reported with CT+IL-2. The most common grade ≥3 adverse events were gastrointestinal toxicity (mainly nausea and diarrhea) and myelosuppression. No relevant differences in clinical outcome were observed from the addition of IL-2 to CT. Future studies investigating the role of T-regulators in chemoimmunotherapeutic regimens could be performed. PMID:21720704

  2. The impact of induction duration and the number of high-dose cycles on the long-term survival of women with metastatic breast cancer treated with high-dose chemotherapy with stem cell rescue: an analysis of sequential phase I/II trials from the Dana-Farber/Beth Israel STAMP program.

    PubMed

    Elias, A D; Ibrahim, J; Richardson, P; Avigan, D; Joyce, R; Reich, E; McCauley, M; Wheeler, C; Frei, E

    2002-01-01

    III were 98, 62, and 39 months from the initiation of induction chemotherapy and 92, 55, and 36 months from last high-dose therapy, respectively. The patient characteristics upon entry into these trials were similar. Important differences were that only those patients achieving a partial response or better to induction therapy were enrolled and analyzed for trials I and II, but all patients were analyzed on an intent-to-treat basis for trial III, including those who did not receive intensification. The median event-free survival (EFS) times from induction chemotherapy were 13, 19, and 27 months for trials I, II, and III, respectively (III versus I + II, P = .0004; III versus I, P = .0005; III versus II, P = .005; II versus I, P = .25). The median overall survival (OS) times from induction chemotherapy were 30, 29, and 57 months for trials I, II, and III, respectively (III versus I + II, P = .002; III versus I, P = .003; III versus II, P = .009; II versus I, P = .47). By multivariate Cox regression, participation in the short induction/double transplantation trial III and having no prior adjuvant chemotherapy remained favorable prognostic factors for both EFS and OS. The presence of visceral disease shortened EFS, and hormone sensitivity was of borderline significance. No substantive differences in the characteristics of the patient populations between the 3 trials appeared to interact with outcomes. In conclusion, we found that single transplantation in responding patients after long induction achieves a small cohort of long-term survivors, similar to the results reported by other transplantation centers. Adding a cycle of single-agent high-dose melphalan in this context delayed median time to relapse but did not affect long-term EFS or OS. The double transplantation approach using CTCb and TxM early in the course of treatment was associated with the best EFS and overall survival and was safe, feasible, and tolerable. Treatment duration was only 14 weeks, and this

  3. Prevalence of menstrual cycles and outcome of 50 pregnancies after high-dose chemotherapy and auto-SCT in non-Hodgkin and Hodgkin lymphoma patients younger than 40 years.

    PubMed

    Akhtar, S; Youssef, I; Soudy, H; Elhassan, T A M; Rauf, S M; Maghfoor, I

    2015-12-01

    Data are limited regarding the prevalence of menstrual cycles and pregnancies after high-dose chemotherapy (HDC) and auto-stem cell transplantation (SCT). Female patients who underwent HDC auto-SCT for non-Hodgkin and Hodgkin lymphoma (1997-2012) were reviewed. The selection criteria were as follows: (1) alive without disease 12 and 24 months after auto-SCT for menstrual cycles and pregnancy, respectively, (2) age <40 years at auto-SCT, and (3) no primary infertility. One-hundred and seventy-six females underwent single auto-SCT. Eighty-nine were eligible for menstrual cycles and pregnancy analysis. Median age at auto-SCT was 25 years (14-40 years), at pregnancy 27 years (20-37 years), median follow-up 65 months (range 24-190). Regular menstrual-cycles resumed in 56/89 patients (63%). Increasing age (P=0.02) and number of prior chemotherapy cycles (P=0.02) are associated with higher risk of amenorrhea. Forty patients tried to get pregnant, 26 (65%) became pregnant 50 times: 43 (86%) live birth, 7 (14%) miscarriage and 2/50 had birth defects. Twenty-four patients practiced breastfeeding (median duration 4 months (1-24 months)). Enough breast milk production was reported 62.5% vs 100% in those patients who did or did not receive above the diaphragm radiation therapy, respectively, (P=0.066). Our data highlights significantly higher than perceived incidence of menstrual cycle resumption, successful pregnancies and breastfeeding after HDC auto-SCT. PMID:26237168

  4. Health related quality of life in stem cell transplantation: clinical and psychometric validation of the questionnaire module, High Dose Chemotherapy (HDC-19).

    PubMed

    Andersson, I; Hjermstad, M; Stockelberg, D; Persson, L O

    2008-01-01

    The objective of this study was to assess the psychometric properties of the HDC-19, a module questionnaire for assessing symptoms and problems of patients undergoing stem cell transplantation (SCT) following high-dose chemotherapy (HDC). It consists of 19 questions and was developed for use in conjunction with EORTC QLQ-C30. Psychometric evaluations were performed according to guidelines recommended by the EORTC. The principal component analyses suggested that nine of the HDC-19 items could be reduced to four components (sexual functioning, future health perspectives, skin irritations and joint/muscle pain). Multitrait scaling analysis showed that most item-scale correlation coefficients met the standards of convergent (>0.40) and discriminant validity. Test-retest reliability coefficients between assessments at inclusion and admission were high, indicating that perceived health status remained virtually unchanged during this period. As expected, correlations between admission and one month after transplantation were considerably lower. The internal consistency of the multi-item scales was also satisfactory, (Cronbach's alpha 0.59-0.87). Overall, the known-groups comparisons showed smaller differences between designated groups than expected. As expected, changes in the HDC-19 mirrored changes in QLQ-C30 'global quality of life'. These results lend support to the validity of the HDC-19 as a supplementary questionnaire for assessing specific health-related quality of life (HRQOL) issues relevant for SCT patients. PMID:18210301

  5. Intermediate dose gemcitabine-cisplatin combination chemotherapy without treatment delay for cytopenia followed by autografting--a new standard of care in relapsed or refractory Hodgkin lymphoma?

    PubMed

    Todd, T; Raj, S; Camilleri, D; Stafford, G; Bulusu, R; Follows, G; Williams, M; Marcus, R

    2009-11-01

    Ten percent to 20% of patients with Hodgkin Lymphoma (HL) are refractory to first-line therapy or relapse. Existing salvage regimens have response rates of 60-85%, considerable toxicity and frequent treatment delay or dose reduction. We report a gemcitabine, cisplatin, and dexamethasone regimen (GemCis) with intensive growth factor and platelet support and no treatment delay. Seventeen patients with relapsed or refractory biopsy proven HL were treated. Toxicity, transfusion requirement, stem cell harvesting and engraftment data were collected. Response assessment was by computed tomography and positron emission tomography. Overall and complete response rates were high (94% and 65%, respectively). There were no episodes of febrile neutropenia, treatment delays or hospital admissions. All 15 patients intended for autograft were successfully harvested. All engrafted successfully with a median time for the entire group to neutrophil engraftment of 14 days. With a median follow-up of 22 months, the median survival has not yet been reached, and the estimated 2-year survival is 88%. GemCis is a well-tolerated outpatient regimen for relapsed/ refractory Hodgkin lymphoma which does not inhibit stem cell mobilisation, gives excellent response rates and compares favourably with previously published salvage regimens using these or other chemotherapy agents. PMID:19418054

  6. Tandem high-dose chemotherapy with thiotepa and busulfan-melphalan and autologous stem cell transplantation in very high-risk neuroblastoma patients.

    PubMed

    Pasqualini, C; Dufour, C; Goma, G; Raquin, M-A; Lapierre, V; Valteau-Couanet, D

    2016-02-01

    High-risk neuroblastoma is characterised by poor long-term survival, especially for very high-risk (VHR) patients (poor response of metastases after induction therapy). We report the results of an intensified high-dose chemotherapy (HDC) strategy to improve the prognosis of VHR patients. This strategy was based on tandem HDC with thiotepa and busulfan-melphalan (Bu-Mel) followed by autologous stem cell transplantation (ASCT). All data were prospectively recorded in the Gustave Roussy Paediatric ASCT database. From April 2004 to August 2011, 26 patients were eligible for tandem HDC. The median age at diagnosis was 4.4 years (1-15.9). All patients had metastatic disease. MYCN was amplified in 5/26 tumours. Despite the cumulative toxicity of alkylating agents, the toxicity of the intensified HDC strategy was manageable. Thiotepa-related toxicity was mainly digestive, whereas sinusoidal obstruction syndrome was the main toxicity observed after Bu-Mel. The 3-year event-free survival of this cohort was 37.3% (21.3-56.7). This strategy will be compared with combined (131)I-mIBG/Bu-Mel in the upcoming SIOPEN VHR Neuroblastoma Protocol. PMID:26524264

  7. Infectious Complications during Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Children with High-Risk or Recurrent Solid Tumors.

    PubMed

    Choi, Young Bae; Yi, Eun Sang; Kang, Ji-Man; Lee, Ji Won; Yoo, Keon Hee; Kim, Yae-Jean; Sung, Ki Woong; Koo, Hong Hoe

    2016-01-01

    We retrospectively analyzed infectious complications during tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) in children and adolescents with high-risk or recurrent solid tumors. A total of 324 patients underwent their first HDCT/auto-SCT between October 2004 and September 2014, and 283 of them proceeded to their second HDCT/auto-SCT (a total of 607 HDCT/auto-SCTs). During the early transplant period of 607 HDCT/auto-SCTs (from the beginning of HDCT to day 30 post-transplant), bacteremia, urinary tract infection (UTI), respiratory virus infection, and varicella zoster virus (VZV) reactivation occurred in 7.1%, 2.3%, 13.0%, and 2.5% of HDCT/auto-SCTs, respectively. The early transplant period of the second HDCT/auto-SCT had infectious complications similar to the first HDCT/auto-SCT. During the late transplant period of HDCT/auto-SCT (from day 31 to 1 year post-transplant), bacteremia, UTI, and VZV reactivation occurred in 7.5%, 2.5%, and 3.9% of patients, respectively. Most infectious complications in the late transplant period occurred during the first 6 months post-transplant. There were no invasive fungal infections during the study period. Six patients died from infectious complications (4 from bacterial sepsis and 2 from respiratory virus infection). Our study suggests that infectious complications are similar following second and first HDCT/auto-SCT in children. PMID:27627440

  8. Phase I trial of (90)Y-ibritumomab tiuxetan in patients with relapsed B-cell non-Hodgkin's lymphoma following high-dose chemotherapy and autologous stem cell transplantation.

    PubMed

    Vose, Julie M; Bierman, Philip J; Loberiza, Fausto R; Bociek, Robert G; Matso, Daniel; Armitage, James O

    2007-04-01

    Between January 2001 and September 2005, 19 patients with progressive B-cell non-Hodgkin's lymphoma were treated with a cohort-specific dose of yttrium-90 ibritumomab tiuxetan (0.10 - 0.20 mCi/kg) to determine appropriate dosing in patients who had previously received high-dose chemotherapy and autologous stem cell transplantation (ASCT). Patients were required to have adequate end organ function and bone marrow status. Patients had been treated with a median of three prior therapies (range, 1 - 9). The median time from ASCT to radioimmunotherapy was 28 months. Hematologic toxicities were dose-limiting and included grade 3 - 4 thrombocytopenia (53%), neutropenia (32%), and anemia (21%). The majority of grade 3 - 4 events occurred at the 0.2 mCi/kg dose level. Nine patients responded (complete response, complete response unconfirmed, or partial response) to the therapy. At a median follow-up of 37 months, the 1-year event-free and overall survival rates were 26% and 57%, respectively. A dose of 0.2 mCi/kg ibritumomab tiuxetan is safe and effective for patients with progressive disease after high-dose chemotherapy and ASCT. PMID:17454625

  9. Combination Chemotherapy with Suboptimal Doses of Benznidazole and Pentoxifylline Sustains Partial Reversion of Experimental Chagas' Heart Disease.

    PubMed

    Vilar-Pereira, Glaucia; Resende Pereira, Isabela; de Souza Ruivo, Leonardo Alexandre; Cruz Moreira, Otacilio; da Silva, Andrea Alice; Britto, Constança; Lannes-Vieira, Joseli

    2016-07-01

    Chronic chagasic cardiomyopathy (CCC) progresses with parasite persistence, fibrosis, and electrical alterations associated with an unbalanced immune response such as high plasma levels of tumor necrosis factor (TNF) and nitric oxide (NO). Presently, the available treatments only mitigate the symptoms of CCC. To improve CCC prognosis, we interfered with the parasite load and unbalanced immune response using the trypanocidal drug benznidazole (Bz) and the immunoregulator pentoxifylline (PTX). C57BL/6 mice chronically infected with the Colombian strain of Trypanosoma cruzi and with signs of CCC were treated for 30 days with a suboptimal dose of Bz (25 mg/kg of body weight), PTX (20 mg/kg), or their combination (Bz plus PTX) and analyzed for electrocardiographic, histopathological, and immunological changes. Bz (76%) and Bz-plus-PTX (79%) therapies decreased parasite loads. Although the three therapies reduced myocarditis and fibrosis and ameliorated electrical alterations, only Bz plus PTX restored normal heart rate-corrected QT (QTc) intervals. Bz-plus-PTX-treated mice presented complementary effects of Bz and PTX, which reduced TNF expression (37%) in heart tissue and restored normal TNF receptor 1 expression on CD8(+) T cells, respectively. Bz (85%) and PTX (70%) therapies reduced the expression of inducible nitric oxide synthase (iNOS/NOS2) in heart tissue, but only Bz (58%) reduced NO levels in serum. These effects were more pronounced after Bz-plus-PTX therapy. Moreover, 30 to 50 days after treatment cessation, reductions of the prolonged QTc and QRS intervals were sustained in Bz-plus-PTX-treated mice. Our findings support the importance of interfering with the etiological agent and immunological abnormalities to improve CCC prognosis, opening an opportunity for a better quality of life for Chagas' disease (CD) patients. PMID:27161638

  10. Combination Chemotherapy with Suboptimal Doses of Benznidazole and Pentoxifylline Sustains Partial Reversion of Experimental Chagas' Heart Disease

    PubMed Central

    Vilar-Pereira, Glaucia; Resende Pereira, Isabela; de Souza Ruivo, Leonardo Alexandre; Cruz Moreira, Otacilio; da Silva, Andrea Alice; Britto, Constança

    2016-01-01

    Chronic chagasic cardiomyopathy (CCC) progresses with parasite persistence, fibrosis, and electrical alterations associated with an unbalanced immune response such as high plasma levels of tumor necrosis factor (TNF) and nitric oxide (NO). Presently, the available treatments only mitigate the symptoms of CCC. To improve CCC prognosis, we interfered with the parasite load and unbalanced immune response using the trypanocidal drug benznidazole (Bz) and the immunoregulator pentoxifylline (PTX). C57BL/6 mice chronically infected with the Colombian strain of Trypanosoma cruzi and with signs of CCC were treated for 30 days with a suboptimal dose of Bz (25 mg/kg of body weight), PTX (20 mg/kg), or their combination (Bz plus PTX) and analyzed for electrocardiographic, histopathological, and immunological changes. Bz (76%) and Bz-plus-PTX (79%) therapies decreased parasite loads. Although the three therapies reduced myocarditis and fibrosis and ameliorated electrical alterations, only Bz plus PTX restored normal heart rate-corrected QT (QTc) intervals. Bz-plus-PTX-treated mice presented complementary effects of Bz and PTX, which reduced TNF expression (37%) in heart tissue and restored normal TNF receptor 1 expression on CD8+ T cells, respectively. Bz (85%) and PTX (70%) therapies reduced the expression of inducible nitric oxide synthase (iNOS/NOS2) in heart tissue, but only Bz (58%) reduced NO levels in serum. These effects were more pronounced after Bz-plus-PTX therapy. Moreover, 30 to 50 days after treatment cessation, reductions of the prolonged QTc and QRS intervals were sustained in Bz-plus-PTX-treated mice. Our findings support the importance of interfering with the etiological agent and immunological abnormalities to improve CCC prognosis, opening an opportunity for a better quality of life for Chagas' disease (CD) patients. PMID:27161638

  11. Randomized trials of high-dose chemotherapy in breast cancer: fraud, the press and the data (or lessons learned in medical policy governing clinical research).

    PubMed Central

    Antman, Karen

    2002-01-01

    High dose therapy for breast cancer remains controversial. Of the 15 randomized trials of high dose therapy in breast cancer reported to date, two South African studies have been discredited leaving 13 remaining studies. Mortality was consistently low, in the 0 to 2.5% range, except for the BCNU containing American Intergroup study, which had a 7.4% toxic mortality rate. Seven of the remaining 13 studies randomized fewer than 200 patients. Three of these small studies have significant differences in disease free survival, and a fourth study has a trend in favor of high dose therapy. The other three small studies cannot exclude a survival difference of 20%. Of the 6 remaining moderately large trials of 219 to 885 randomized patients, 5 are adjuvant studies and one included patients with metastatic disease. Of the five adjuvant trials, four have significant differences in relapse rate favoring the high dose arm, and the remaining study has a trend (with a high dose sequential single agent design rather than combination therapy as in the other studies). A planned subset analysis of the first 284 patients in the largest study funded by the Dutch insurance industry showed a significant advantage for high dose therapy. Given the 2-year median time to relapse and an addition 2-year median to death after relapse, the follow up for survival of 3-5 years on these studies is still short. In the only moderately sized metastatic trial from the National Cancer Institute of Canada with a very short median follow-up of 19 months, a significant difference in disease free survival has emerged, with no difference in survival. PMID:12053718

  12. Gonadal damage from chemotherapy and radiotherapy.

    PubMed

    Howell, S; Shalet, S

    1998-12-01

    Treatment with cytotoxic chemotherapy and radiotherapy is associated with significant gonadal damage in men and women. Alkylating agents such as cyclophosphamide and procarbazine are the most common agents implicated. The vast majority of men receiving procarbazine-containing regimens for the treatment of lymphomas become permanently infertile. Cisplatin-based chemotherapy for testicular cancer results in temporary azoospermia in most men, with a recovery of spermatogenesis in about 50% after 2 years and in 80% after 5 years. There is also evidence of Leydig cell impairment in a proportion of these men, although the clinical significance of this is not clear. The germinal epithelium is very sensitive to radiation-induced damage, with changes to spermatogonia occurring following as little as 0.1 Gy and permanent infertility after fractionated doses of 2 Gy and above. Cytotoxic-induced premature ovarian failure is age- and drug-dependent and ensues in approximately half of women treated with procarbazine-containing chemotherapy for lymphomas. High-dose chemotherapy, total body irradiation, and irradiation at an ovarian dose above 6 Gy usually result in permanent ovarian failure. The course of ovarian function after chemotherapy is variable, and late recovery occurs in some patients. Several methods of preserving gonadal function during potentially sterilizing treatment have been considered. Currently, sperm banking remains the only proven method in men, although hormonal manipulation to enhance the recovery of spermatogenesis and cryopreservation of testicular germ cells are possibilities for the future. Transposition of the ovaries to allow better shielding during radiotherapy is of use in some women, and the prospect of cryopreservation and reimplantation of ovarian tissue is promising. PMID:9922915

  13. Multimodal treatment of metastatic thymic carcinoma including high-dose chemotherapy with autologous stem cell transplantation: report of a case with more than 4-year disease-free survival.

    PubMed

    Geffen, D B; Benharroch, D; Yellin, A; Ariad, S; Or, R; Cohen, Y

    2001-12-01

    Thymic carcinoma is a rare epithelial malignancy differentiated from thymoma by the presence of cytologically malignant cells. There are few reports of the treatment of locally advanced or metastatic thymic carcinoma. We describe a patient who sought treatment for thymic carcinoma metastatic to pleura, pericardium, retroperitoneum, and neck nodes. He was treated with neoadjuvant etoposide, ifosfamide, and cisplatin, and underwent resection. We then administered high-dose chemotherapy with autologous stem cell support, followed by radiation therapy. The patient remains in complete remission more than 4 years after diagnosis. To our knowledge, this is the first report of metastatic thymic carcinoma treated with neoadjuvant therapy and postoperative high-dose chemotherapy. Metastatic thymic carcinoma may be curable by aggressive combined therapies. PMID:11801755

  14. [Cases of advanced cholangiocarcinoma showing partial response by the combination chemotherapy including protracted continuous infusion of 5-FU combined with intravenous administration of low-dose leucovorin and intra-arterial administration of MMC and CQ].

    PubMed

    Tsushima, K; Sakata, Y; Shiratori, Y; Sakamoto, J; Koeda, J; Yamada, Y; Soma, N; Tamura, K; Yoshiwara, A; Soma, Y

    1991-12-01

    We treated a patient with advanced cholangiocarcinoma with a new combination chemotherapy (modified MQF). The regimen consisted of intra-arterial administration of MMC (20 mg/body) and CQ (4 mg/body), protracted continuous infusion of 5-FU (500 mg/body) and intravenous administration of low-dose leucovorin (30 mg/body). More than 50% reduction in the liver tumor for over 4 weeks was obtained by the therapy. As for toxicity, diarrhea and stomatitis were observed. PMID:1660702

  15. Preparation and clinical evaluation of a novel lozenge containing polaprezinc, a zinc-L-carnosine, for prevention of oral mucositis in patients with hematological cancer who received high-dose chemotherapy.

    PubMed

    Hayashi, Hiroko; Kobayashi, Ryo; Suzuki, Akio; Yamada, Yuto; Ishida, Masayuki; Shakui, Toshinobu; Kitagawa, Junichi; Hayashi, Hideki; Sugiyama, Tadashi; Takeuchi, Hirofumi; Tsurumi, Hisashi; Itoh, Yoshinori

    2016-08-01

    We previously reported that oral ingestion of polaprezinc, a zinc-L-carnosine, suspended in sodium alginate solution prevents oral mucositis in patients receiving radiotherapy or high-dose chemotherapy. In the present study, we developed a novel preparation of polaprezinc and evaluated clinical effect of the lozenge preparation in patients receiving high-dose chemotherapy for hematopoietic stem cell transplantation. The preparation contained 18.75 mg polaprezinc in a tablet and showed an excellent uniformity and stability up to 24 weeks after storage under room temperature. The incidence rate of grade ≥ 2 oral mucositis was 74 % in patients without premedication, whereas the rate was remarkably reduced in patients receiving the suspension (23 %) or lozenge (13 %) of polaprezinc (P < 0.01). The use of non-opioid analgesic drugs such as anti-inflammatory agents and local anesthetics for oral pain was also greatly reduced by polaprezinc suspension or its lozenge (16 % for suspension and 13 % for lozenge compared with 89 % with no premedication, P < 0.01). These findings suggest that polaprezinc lozenge is simple to apply and highly effective for prevention of oral mucositis associated with high-dose chemotherapy for hematopoietic stem cell transplantation. PMID:27418192

  16. High-Dose Chemotherapy and Autologous Stem Cell Transplantation in Children with High-Risk or Recurrent Bone and Soft Tissue Sarcomas

    PubMed Central

    2016-01-01

    Despite increasing evidence that high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) might improve the survival of patients with high-risk or recurrent solid tumors, therapy effectiveness for bone and soft tissue sarcoma treatment remains unclear. This study retrospectively investigated the feasibility and effectiveness of HDCT/auto-SCT for high-risk or recurrent bone and soft tissue sarcoma. A total of 28 patients (18 high-risk and 10 recurrent) underwent single or tandem HDCT/auto-SCT between October 2004 and September 2014. During follow-up of a median 15.3 months, 18 patients exhibited disease progression and 2 died of treatment-related toxicities (1 veno-occlusive disease and 1 sepsis). Overall, 8 patients remained alive and progression-free. The 3-year overall survival (OS) and event-free survival (EFS) rates for all 28 patients were 28.7% and 26.3%, respectively. In the subgroup analysis, OS and EFS rates were higher in patients with complete or partial remission prior to HDCT/auto-SCT than in those with worse responses (OS, 39.1% vs. 0.0%, P = 0.002; EFS, 36.8% vs. 0.0%, P < 0.001). Therefore, careful selection of patients who can benefit from HDCT/auto-SCT and maximal effort to reduce tumor burden prior to treatment will be important to achieve favorable outcomes in patients with high-risk or recurrent bone and soft tissue sarcomas. PMID:27366002

  17. Dose-intensified chemotherapy alone or in combination with mogamulizumab in newly diagnosed aggressive adult T-cell leukaemia-lymphoma: a randomized phase II study.

    PubMed

    Ishida, Takashi; Jo, Tatsuro; Takemoto, Shigeki; Suzushima, Hitoshi; Uozumi, Kimiharu; Yamamoto, Kazuhito; Uike, Naokuni; Saburi, Yoshio; Nosaka, Kisato; Utsunomiya, Atae; Tobinai, Kensei; Fujiwara, Hiroshi; Ishitsuka, Kenji; Yoshida, Shinichiro; Taira, Naoya; Moriuchi, Yukiyoshi; Imada, Kazunori; Miyamoto, Toshihiro; Akinaga, Shiro; Tomonaga, Masao; Ueda, Ryuzo

    2015-06-01

    This multicentre, randomized, phase II study was conducted to examine whether the addition of mogamulizumab, a humanized anti-CC chemokine receptor 4 antibody, to mLSG15, a dose-intensified chemotherapy, further increases efficacy without compromising safety of patients with newly diagnosed aggressive adult T-cell leukaemia-lymphoma (ATL). Patients were assigned 1:1 to receive mLSG15 plus mogamulizumab or mLSG15 alone. The primary endpoint was the complete response rate (%CR); secondary endpoints included the overall response rate (ORR) and safety. The %CR and ORR in the mLSG15-plus-mogamulizumab arm (n = 29) were 52% [95% confidence interval (CI), 33-71%] and 86%, respectively; the corresponding values in the mLSG15 arm (n = 24) were 33% (95% CI, 16-55%) and 75%, respectively. Grade ≥ 3 treatment-emergent adverse events, including anaemia, thrombocytopenia, lymphopenia, leucopenia and decreased appetite, were observed more frequently (≥10% difference) in the mLSG15-plus-mogamulizumab arm. Several adverse events, including skin disorders, cytomegalovirus infection, pyrexia, hyperglycaemia and interstitial lung disease, were observed only in the mLSG15-plus-mogamulizumab arm. Although the combination strategy showed a potentially less favourable safety profile, a higher %CR was achieved, providing the basis for further investigation of this novel treatment for newly diagnosed aggressive ATL. This study was registered at ClinicalTrials.gov, identifier: NCT01173887. PMID:25733162

  18. Improved outcome of patients with relapsed/refractory Hodgkin lymphoma with a new fotemustine-based high-dose chemotherapy regimen.

    PubMed

    Musso, Maurizio; Messina, Giuseppe; Di Renzo, Nicola; Di Carlo, Paolo; Vitolo, Umberto; Scalone, Renato; Marcacci, Gianpaolo; Scalzulli, Potito R; Moscato, Tiziana; Matera, Rossella; Crescimanno, Alessandra; Santarone, Stella; Orciuolo, Enrico; Merenda, Anxur; Pavone, Vincenzo; Pastore, Domenico; Donnarumma, Daniela; Carella, Angelo M; Ciochetto, Chiara; Cascavilla, Nicola; Mele, Anna; Lanza, Francesco; Di Nicola, Massimo; Bonizzoni, Erminio; Pinto, Antonello

    2016-01-01

    High-dose chemotherapy (HDT) with autologous stem cell transplantation is the standard of care for relapsed/refractory (RR) Hodgkin lymphoma (HL). Given that HDT may cure a sizeable proportion of patients refractory to first salvage, development of newer conditioning regimens remains a priority. We present the results of a novel HDT regimen in which carmustine was substituted by a third-generation chloroethylnitrosourea, fotemustine, with improved pharmacokinetics and safety (FEAM; fotemustine, etoposide, cytarabine, melphalan) in 122 patients with RR-HL accrued into a prospective registry-based study. Application of FEAM resulted in a 2-year progression-free survival (PFS) of 73·8% [95% confidence interval (CI), 0·64-0·81] with median PFS, overall survival and time to progression yet to be reached. The 2-year risk of progression adjusted for the competitive risk of death was 19·4% (95% CI, 0·12-0·27) for the entire patient population. Most previously established independent risk factors, except for fluorodeoxyglucose ((18) (F) FDG)-uptake, were unable to predict for disease progression and survival after FEAM. Although 32% of patients had (18) (F) FDG-positrin emission tomography-positive lesions before HDT, the 2-year risk of progression adjusted for competitive risk of death was 19·4% (95% CI; 0·12-0·27). No unusual acute toxicities or early/late pulmonary adverse events were registered. FEAM emerges as an ideal HDT regimen for RR-HL patients typically pre-exposed to lung-damaging treatments. PMID:26458240

  19. The presence of genomic imbalances is associated with poor outcome in patients with burkitt lymphoma treated with dose-intensive chemotherapy including rituximab.

    PubMed

    Forero-Castro, Maribel; Robledo, Cristina; Lumbreras, Eva; Benito, Rocio; Hernández-Sánchez, Jesús M; Hernández-Sánchez, María; García, Juan L; Corchete-Sánchez, Luis A; Tormo, Mar; Barba, Pere; Menárguez, Javier; Ribera, Jordi; Grande, Carlos; Escoda, Lourdes; Olivier, Carmen; Carrillo, Estrella; García de Coca, Alfonso; Ribera, Josep-María; Hernández-Rivas, Jesús M

    2016-02-01

    The introduction of Rituximab has improved the outcome and survival rates of Burkitt lymphoma (BL). However, early relapse and refractoriness are current limitations of BL treatment and new biological factors affecting the outcome of these patients have not been explored. This study aimed to identify the presence of genomic changes that could predict the response to new therapies in BL. Forty adolescent and adult BL patients treated with the Dose-Intensive Chemotherapy Including Rituximab (Burkimab) protocol (Spanish Programme for the Study and Treatment of Haematological Malignancies; PETHEMA) were analysed using array-based comparative genomic hybridization (CGH). In addition, the presence of TP53, TCF3 (E2A), ID3 and GNA13 mutations was assessed by next-generation sequencing (NGS). Ninety-seven per cent of the patients harboured genomic imbalances. Losses on 11q, 13q, 15q or 17p were associated with a poor response to Burkimab therapy (P = 0·038), shorter progression-free survival (PFS; P = 0·007) and overall survival (OS; P = 0·009). The integrative analysis of array-CGH and NGS showed that 26·3% (5/19) and 36·8% (7/19) of patients carried alterations in the TP53 and TCF3 genes, respectively. TP53 alterations were associated with shorter PFS (P = 0·011) while TCF3 alterations were associated with shorter OS (P = 0·032). Genetic studies could be used for risk stratification of BL patients treated with the Burkimab protocol. PMID:26567765

  20. Effects of Exercise in Combination With Epoetin Alfa During High-Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation for Multiple Myeloma

    PubMed Central

    Coleman, Elizabeth A.; Coon, Sharon K.; Kennedy, Robert L.; Lockhart, Kimberly D.; Stewart, Carol B.; Anaissie, Elias J.; Barlogie, Bart

    2008-01-01

    Purpose/Objectives To determine the effect of aerobic and strength resistance training and epoetin alfa (EPO) therapy on transfusions, stem cell collections, transplantation recovery, and multiple myeloma treatment response. Design Randomized clinical trial. Setting A myeloma research and therapy center in the south central United States. Sample 135 patients with multiple myeloma, 120 evaluable. Methods Random assignment to exercise or usual care groups. All patients received EPO based on an algorithm. Aerobic capacity, using the six-minute walk test, was assessed prior to induction chemotherapy, prior to stem cell mobilization, and following stem cell collection for all patients and before and after transplantation for patients continuing in the study. Data analysis included analysis of variance to compare other outcome variables by groups. Main Research Variables Number of red blood cell and platelet transfusions during transplantation, number of attempts at and total number of days of stem cell collection, time to recovery after transplantation, and response to intensive therapy for multiple myeloma. Findings Recovery and treatment response were not significantly different between groups after transplantation. The exercise group had significantly fewer red blood cell transfusions and fewer attempts at stem cell collection. Serious adverse events were similar in each group. Conclusions Exercise with prophylactic EPO therapy reduces the number of RBC transfusions and attempts at stem cell collection for patients receiving intensive treatment for multiple myeloma. Implications for Nursing Exercise is safe and has many physiologic benefits for patients receiving multiple myeloma treatment. PMID:18467280

  1. Chemotherapy and Your Mouth

    MedlinePlus

    ... Health > Chemotherapy and Your Mouth Chemotherapy and Your Mouth Main Content Are You Being Treated With Chemotherapy ... Back to Top How Does Chemotherapy Affect the Mouth? Chemotherapy is the use of drugs to treat ...

  2. A Phase I/II Radiation Dose Escalation Study With Concurrent Chemotherapy for Patients With Inoperable Stages I to III Non-Small-Cell Lung Cancer: Phase I Results of RTOG 0117

    SciTech Connect

    Bradley, Jeffrey D.; Moughan, Jennifer; Graham, Mary V.; Byhardt, Roger; Govindan, Ramaswamy; Fowler, Jack; Purdy, James A.; Michalski, Jeff M.; Gore, Elizabeth; Choy, Hak

    2010-06-01

    Purpose: In preparation for a Phase III comparison of high-dose versus standard-dose radiation therapy, this Phase I/II study was initiated to establish the maximum tolerated dose of radiation therapy in the setting of concurrent chemotherapy, using three-dimensional conformal radiation therapy for non-small-cell lung cancer. Methods and Materials: Eligibility included patients with histologically proven, unresectable Stages I to III non-small-cell lung cancer. Concurrent chemotherapy consisted of paclitaxel, 50 mg/m{sup 2}, and carboplatin, AUC of 2, given weekly. The radiation dose was to be sequentially intensified by increasing the daily fraction size, starting from 75.25 Gy/35 fractions. Results: The Phase I portion of this study accrued 17 patients from 10 institutions and was closed in January 2004. After the initial 8 patients were accrued to cohort 1, the trial closed temporarily on September 26, 2002, due to reported toxicity. Two acute treatment-related dose-limiting toxicities (DLTs) were reported at the time: a case of grade 5 and grade 3 radiation pneumonitis. The protocol, therefore, was revised to de-escalate the radiation therapy dose (74 Gy/37 fractions). Patients in cohort 1 continued to develop toxicity, with 6/8 (75%) patients eventually developing grade >=3 events. Cohort 2 accrued 9 patients. There was one DLT, a grade 3 esophagitis, in cohort 2 in the first 5 patients (1/5 patients) and no DLTs for the next 2 patients (0/2 patients). Conclusions: The maximum tolerated dose was determined to be 74 Gy/37 fractions (2.0 Gy per fraction) using three-dimensional conformal radiation therapy with concurrent paclitaxel and carboplatin therapy. This dose level in the Phase II portion has been well tolerated, with low rates of acute and late lung toxicities.

  3. A randomized comparative study of antiemetic prophylaxis with ondansentron in a single 32-mg loading dose versus 8 mg every 6 h in patients undergoing cisplatin-based chemotherapy.

    PubMed

    Tsavaris, N; Fountzilas, G; Mylonakis, N; Athanassiadis, A; Kosmas, C; Karakousis, C; Bacoyiannis, C; Kosmidis, P

    1998-01-01

    In several studies a single dose of 32 mg was compared to an ondansentron (OND) administration schedule of every 6 h, yielding no differences in overall efficacy. The aim of this randomized comparative study was to identify differences of these two schedules on an hour-to-hour control of nausea and vomiting, during the first 24 h in patients receiving cisplatin (CDDP)-based chemotherapy. One hundred ten patients were randomly assigned to two groups (A and B); all received combination chemotherapy with CDDP at a dose of 100 mg/m2. OND was administered as follows: group A: 8 mg, 30 min before the infusion of CDDP, and repeated every 6 h after the first dose (totally 4 doses) in the first 24 h, and group B: 32 mg before CDDP, as a loading dose and this was the total dose for the first 24 h. No overall difference was noticed during the first 24 h, as well as the next 3 days from the infusion of CDDP in the intensity of vomits, vomits without gastric content (retches), and nausea. In a more detailed monitoring of the distribution of emetic episodes during the first 24 h, there were important differences between these two antiemetic schedules: for group A an increased vomiting with or without gastric content between midnight and 6 p.m. was observed, and for group B between 6 p.m. and midnight (vomits with p 0.03, and without gastric content p 0.02). Preloading with the total 24-hour dose of OND 32 mg exhibits a more potent antiemetic activity during the initial 18 h, becoming weaker over the last 5 h of the first day, whereas the every-6-hour schedule leaves periods of poor emesis control between dosing intervals. PMID:9778615

  4. [Rectal cancer and adjuvant chemotherapy: which conclusions?].

    PubMed

    Bachet, J-B; Rougier, P; de Gramont, A; André, T

    2010-01-01

    Adenocarcinoma of the rectum represents about a third of cases of colorectal cancer, with an annual incidence of 12,000 cases in France. On the contrary of colon cancer, the benefice of adjuvant chemotherapy in rectal cancer has not been definitively proved, more because this question was assessed in few recent studies than because negative results. Preoperative radiochemotherapy is now the reference treatment for mid and lower rectal cancers, and allow to increase the local control without improvement of progression free survival and overall survival. The data of the "historical studies" of adjuvant treatment in rectal cancer published before 1990, of the meta-analysis of adjuvant trials in rectal cancer and of the QUASAR study suggest that adjuvant chemotherapy with fluoropyrimidines (intravenous or oral), in absence of pre-operative treatment, decrease the risk of metastatic relapse after curative surgery for a rectal cancer of stage II or III. This benefice seems similar to the one observed in colon cancer. In the EORTC radiotherapy group trial 22921, an adjuvant chemotherapy with 5-fluorouracil and low dose of leucovorin was not associated with a significantly improvement of overall survival but, despite the fact that only 42.9% of patients received all planed cycles, the progression free survival was increased (not significantly) in groups receiving adjuvant chemotherapy. The French recommendations are to discuss the indication of adjuvant chemotherapy by fluoropyrimidines in cases of stage III rectal cancer on histopathologic reports and no chemotherapy in case of stade II. Despite the fact that none study have assessed a combination of fluoropyrimidines and oxaliplatin in adjuvant setting in rectal cancer, like in colon cancer, the Folfox4, modified Folfox6 or Xelox regimens are valid options in stage III (experts opinion). In cases of pathologic complete remission or in absence of involved nodes, the benefice of adjuvant chemotherapy is not assessed. In

  5. Discovery and Delivery of Synergistic Chemotherapy Drug Combinations to Tumors

    NASA Astrophysics Data System (ADS)

    Camacho, Kathryn Militar

    Chemotherapy combinations for cancer treatments harbor immense therapeutic potentials which have largely been untapped. Of all diseases, clinical studies of drug combinations are the most prevalent in oncology, yet their effectiveness is disputable, as complete tumor regressions are rare. Our research has been devoted towards developing delivery vehicles for combinations of chemotherapy drugs which elicit significant tumor reduction yet limit toxicity in healthy tissue. Current administration methods assume that chemotherapy combinations at maximum tolerable doses will provide the greatest therapeutic effect -- a presumption which often leads to unprecedented side effects. Contrary to traditional administration, we have found that drug ratios rather than total cumulative doses govern combination therapeutic efficacy. In this thesis, we have developed nanoparticles to incorporate synergistic ratios of chemotherapy combinations which significantly inhibit cancer cell growth at lower doses than would be required for their single drug counterparts. The advantages of multi-drug incorporation in nano-vehicles are many: improved accumulation in tumor tissue via the enhanced permeation and retention effect, limited uptake in healthy tissue, and controlled exposure of tumor tissue to optimal synergistic drug ratios. To exploit these advantages for polychemotherapy delivery, two prominent nanoparticles were investigated: liposomes and polymer-drug conjugates. Liposomes represent the oldest class of nanoparticles, with high drug loading capacities and excellent biocompatibility. Polymer-drug conjugates offer controlled drug incorporations through reaction stoichiometry, and potentially allow for delivery of precise ratios. Here, we show that both vehicles, when armed with synergistic ratios of chemotherapy drugs, significantly inhibit tumor growth in an aggressive mouse breast carcinoma model. Furthermore, versatile drug incorporation methods investigated here can be broadly

  6. Dexa-BEAM: an effective regimen for cytoreduction prior to high-dose chemotherapy with autologous stem cell support for patients with relapsed/refractory mantle-cell lymphoma.

    PubMed

    Josting, A; Reiser, M; Wickramanayake, P D; Rueffer, U; Draube, A; Söhngen, D; Tesch, H; Wolf, J; Diehl, V; Engert, A

    2000-03-01

    Mantle-cell lymphoma (MCL) is not a curable disease using conventional chemotherapy. Patients with MCL have the shortest median time to progression and the shortest median survival of all lymphoma subtypes after first-line treatment. In the present study we determined the efficacy of maximal cytoreductive therapy with up to four cycles of Dexa-BEAM (dexamethasone, carmustine [BCNU], etoposide, cytarabine, and melphalan) followed by high-dose chemotherapy (HDCT) and autologous hematopoietic stem cell support (ASCT) for patients with advanced relapsed or refractory MCL. Nine consecutive patients with relapsed or refractory MCL were included. Three patients had partial remission (PR), three patients progressive disease (PD) upon first line tretment, and three patients first or subsequent relapse. After 2 to four cycles of Dexa-BEAM eight patients achieved complete remission (CR), resulting in a response rate of 88%. Six of 8 patients responding to Dexa-BEAM received high-dose chemotherapy HDCT (BEAM) and autologous hematopoietic stem cell transplantation (ASCT). With a median follow up of 24 months six patients are alive. Five of those six patients are still in contiuous CR (range 13-54 months). PMID:10721785

  7. Phase II Study of Accelerated High-Dose Radiotherapy With Concurrent Chemotherapy for Patients With Limited Small-Cell Lung Cancer: Radiation Therapy Oncology Group Protocol 0239

    SciTech Connect

    Komaki, Ritsuko; Paulus, Rebecca; Ettinger, David S.; Videtic, Gregory M.M.; Bradley, Jeffrey D.; Glisson, Bonnie S.; Sause, William T.; Curran, Walter J.; Choy, Hak

    2012-07-15

    Purpose: To investigate whether high-dose thoracic radiation given twice daily during cisplatin-etoposide chemotherapy for limited small-cell lung cancer (LSCLC) improves survival, acute esophagitis, and local control rates relative to findings from Intergroup trial 0096 (47%, 27%, and 64%). Patients and Methods: Patients were accrued over a 3-year period from 22 US and Canadian institutions. Patients with LSCLC and good performance status were given thoracic radiation to 61.2 Gy over 5 weeks (daily 1.8-Gy fractions on days 1-22, then twice-daily 1.8-Gy fractions on days 23-33). Cisplatin (60 mg/m{sup 2} IV) was given on day 1 and etoposide (120 mg/m{sup 2} IV) on days 1-3 and days 22-24, followed by 2 cycles of cisplatin plus etoposide alone. Patients who achieved complete response were offered prophylactic cranial irradiation. Endpoints included overall and progression-free survival; severe esophagitis (Common Toxicity Criteria v 2.0) and treatment-related fatalities; response (Response Evaluation Criteria in Solid Tumors); and local control. Results: Seventy-two patients were accrued from June 2003 through May 2006; 71 were evaluable (median age 63 years; 52% female; 58% Zubrod 0). Median survival time was 19 months; at 2 years, the overall survival rate was 36.6% (95% confidence interval [CI] 25.6%-47.7%), and progression-free survival 19.7% (95% CI 11.4%-29.6%). Thirteen patients (18%) experienced severe acute esophagitis, and 2 (3%) died of treatment-related causes; 41% achieved complete response, 39% partial response, 10% stable disease, and 6% progressive disease. The local control rate was 73%. Forty-three patients (61%) received prophylactic cranial irradiation. Conclusions: The overall survival rate did not reach the projected goal; however, rates of esophagitis were lower, and local control higher, than projected. This treatment strategy is now one of three arms of a prospective trial of chemoradiation for LSCLC (Radiation Therapy Oncology Group 0538

  8. Pemetrexed had significantly better clinical efficacy in patients with stage IV lung adenocarcinoma with susceptible EGFR mutations receiving platinum-based chemotherapy after developing resistance to the first-line gefitinib treatment

    PubMed Central

    Yang, Chih-Jen; Tsai, Ming-Ju; Hung, Jen-Yu; Liu, Ta-Chih; Chou, Shah-Hwa; Lee, Jui-Ying; Hsu, Jui-Sheng; Tsai, Ying-Ming; Huang, Ming-Shyan; Chong, Inn-Wen

    2016-01-01

    Background Increased evidences show that epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors such as gefitinib could prolong progression-free survival (PFS) compared with cytotoxic chemotherapy for metastatic lung nonsquamous cell carcinoma harboring susceptible EGFR mutation, and gefitinib was served as the first-line therapy. However, acquired resistance is inevitable, but the salvage therapies are still unclear. Patients and methods We designed a retrospective study of the salvage therapy and enrolled patients with stage IV lung adenocarcinoma who had mutated EGFR and developed an acquired resistance to the first-line gefitinib in two university-affiliated hospitals in Taiwan during June 2011 to December 2014. Age, sex, smoking history, EGFR gene mutation, performance statuses, response rate, PFS2 (the PFS in salvage therapy), and overall survival (OS2, the OS in salvage therapy) were recorded. Results Two hundred and nine patients with mutated EGFR and who took gefitinib as first-line therapy were identified in the period, and a total of 98 patients who had been treated with salvage therapy with cytotoxic chemotherapy or erlotinib were eligible for this study. The overall response rate of second salvage therapy is 13%, and none of them received erlotinib. Patients who received chemotherapy had a trend for better PFS2 than those who received erlotinib (4.3 months vs 3.0 months, P=0.1417) but not in OS. Furthermore, patients who received platinum-based doublet had a trend for better PFS2 and a significantly better OS2 than those who received chemotherapy without platinum (PFS2: 4.9 months vs 2.6 months, P=0.0584; OS2: 16.1 months vs 6.7 months, P=0.0007). Analyses of the patients receiving platinum-based doublet showed that patients receiving pemetrexed had a significantly better PFS2 (6.4 months vs 4.1 months, P=0.0083) and a trend for better OS2 than those without pemetrexed treatment. Conclusion Pemetrexed-based platinum chemotherapy may be the

  9. The addition of rituximab to fludarabine and cyclophosphamide chemotherapy results in a significant improvement in overall survival in patients with newly diagnosed mantle cell lymphoma: results of a randomized UK National Cancer Research Institute trial

    PubMed Central

    Rule, Simon; Smith, Paul; Johnson, Peter W.M.; Bolam, Simon; Follows, George; Gambell, Joanne; Hillmen, Peter; Jack, Andrew; Johnson, Stephen; Kirkwood, Amy A; Kruger, Anton; Pocock, Christopher; Seymour, John F.; Toncheva, Milena; Walewski, Jan; Linch, David

    2016-01-01

    Mantle cell lymphoma is an incurable and generally aggressive lymphoma that is more common in elderly patients. Whilst a number of different chemotherapeutic regimens are active in this disease, there is no established gold standard therapy. Rituximab has been used widely to good effect in B-cell malignancies but there is no evidence that it improves outcomes when added to chemotherapy in this disease. We performed a randomized, open-label, multicenter study looking at the addition of rituximab to the standard chemotherapy regimen of fludarabine and cyclophosphamide in patients with newly diagnosed mantle cell lymphoma. A total of 370 patients were randomized. With a median follow up of six years, rituximab improved the median progression-free survival from 14.9 to 29.8 months (P<0.001) and overall survival from 37.0 to 44.5 months (P=0.005). This equates to absolute differences of 9.0% and 22.1% for overall and progression-free survival, respectively, at two years. Overall response rates were similar, but complete response rates were significantly higher in the rituximab arm: 52.7% vs. 39.9% (P=0.014). There was no clinically significant additional toxicity observed with the addition of rituximab. Overall, approximately 18% of patients died of non-lymphomatous causes, most commonly infections. The addition of rituximab to fludarabine and cyclophosphamide chemotherapy significantly improves outcomes in patients with mantle cell lymphoma. However, these regimens have significant late toxicity and should be used with caution. This trial has been registered (ISRCTN81133184 and clinicaltrials.gov:00641095) and is supported by the UK National Cancer Research Network. PMID:26611473

  10. The addition of rituximab to fludarabine and cyclophosphamide chemotherapy results in a significant improvement in overall survival in patients with newly diagnosed mantle cell lymphoma: results of a randomized UK National Cancer Research Institute trial.

    PubMed

    Rule, Simon; Smith, Paul; Johnson, Peter W M; Bolam, Simon; Follows, George; Gambell, Joanne; Hillmen, Peter; Jack, Andrew; Johnson, Stephen; Kirkwood, Amy A; Kruger, Anton; Pocock, Christopher; Seymour, John F; Toncheva, Milena; Walewski, Jan; Linch, David

    2016-02-01

    Mantle cell lymphoma is an incurable and generally aggressive lymphoma that is more common in elderly patients. Whilst a number of different chemotherapeutic regimens are active in this disease, there is no established gold standard therapy. Rituximab has been used widely to good effect in B-cell malignancies but there is no evidence that it improves outcomes when added to chemotherapy in this disease. We performed a randomized, open-label, multicenter study looking at the addition of rituximab to the standard chemotherapy regimen of fludarabine and cyclophosphamide in patients with newly diagnosed mantle cell lymphoma. A total of 370 patients were randomized. With a median follow up of six years, rituximab improved the median progression-free survival from 14.9 to 29.8 months (P<0.001) and overall survival from 37.0 to 44.5 months (P=0.005). This equates to absolute differences of 9.0% and 22.1% for overall and progression-free survival, respectively, at two years. Overall response rates were similar, but complete response rates were significantly higher in the rituximab arm: 52.7% vs. 39.9% (P=0.014). There was no clinically significant additional toxicity observed with the addition of rituximab. Overall, approximately 18% of patients died of non-lymphomatous causes, most commonly infections. The addition of rituximab to fludarabine and cyclophosphamide chemotherapy significantly improves outcomes in patients with mantle cell lymphoma. However, these regimens have significant late toxicity and should be used with caution. This trial has been registered (ISRCTN81133184 and clinicaltrials.gov:00641095) and is supported by the UK National Cancer Research Network. PMID:26611473

  11. γ-Herpesvirus Load as Surrogate Marker of Early Death in HIV-1 Lymphoma Patients Submitted to High Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation

    PubMed Central

    Pratesi, Chiara; Zanussi, Stefania; Tedeschi, Rosamaria; Bortolin, Maria Teresa; Talamini, Renato; Rupolo, Maurizio; Scaini, Chiara; Basaglia, Giancarlo; Di Maso, Matteo; Mazzucato, Mario; Zanet, Ernesto; Tirelli, Umberto; Michieli, Mariagrazia; Carbone, Antonino; De Paoli, Paolo

    2015-01-01

    Autologous stem cell transplantation (ASCT) is a feasible procedure for human immunodeficiency virus-1 (HIV-1) lymphoma patients, whose underlying disease and intrinsic HIV-1- and ASCT-associated immunodeficiency might increase the risk for γ-herpesvirus load persistence and/or reactivation. We evaluated this hypothesis by investigating the levels of Epstein-Barr virus (EBV)- and Kaposi sarcoma-associated herpesvirus (KSHV)-DNA levels in the peripheral blood of 22 HIV-1-associated lymphoma patients during ASCT, highlighting their relationship with γ-herpesvirus lymphoma status, immunological parameters, and clinical events. EBV-DNA was detected in the pre-treatment plasma and peripheral blood mononuclear cells (PBMCs) of 12 (median 12135 copies/mL) and 18 patients (median 417 copies/106 PBMCs), respectively; the values in the two compartments were correlated (r = 0.77, p = 0.0001). Only EBV-positive lymphomas showed detectable levels of plasma EBV-DNA. After debulking chemotherapy, plasma EBV-DNA was associated with lymphoma chemosensitivity (p = 0.03) and a significant higher mortality risk by multivariate Cox analysis adjusted for EBV-lymphoma status (HR, 10.46, 95% CI, 1.11–98.32, p = 0.04). After infusion, EBV-DNA was detectable in five EBV-positive lymphoma patients who died within six months. KSHV-DNA load was positive in only one patient, who died from primary effusion lymphoma. Fluctuations in levels of KSHV-DNA reflected the patient’s therapy and evolution of his underlying lymphoma. Other γ-herpesvirus-associated malignancies, such as multicentric Castleman disease and Kaposi sarcoma, or end-organ complications after salvage treatment were not found. Overall, these findings suggest a prognostic and predictive value of EBV-DNA and KSHV-DNA, the monitoring of which could be a simple, complementary tool for the management of γ-herpesvirus-positive lymphomas in HIV-1 patients submitted to ASCT. PMID:25668032

  12. γ-Herpesvirus load as surrogate marker of early death in HIV-1 lymphoma patients submitted to high dose chemotherapy and autologous peripheral blood stem cell transplantation.

    PubMed

    Pratesi, Chiara; Zanussi, Stefania; Tedeschi, Rosamaria; Bortolin, Maria Teresa; Talamini, Renato; Rupolo, Maurizio; Scaini, Chiara; Basaglia, Giancarlo; Di Maso, Matteo; Mazzucato, Mario; Zanet, Ernesto; Tirelli, Umberto; Michieli, Mariagrazia; Carbone, Antonino; De Paoli, Paolo

    2015-01-01

    Autologous stem cell transplantation (ASCT) is a feasible procedure for human immunodeficiency virus-1 (HIV-1) lymphoma patients, whose underlying disease and intrinsic HIV-1- and ASCT-associated immunodeficiency might increase the risk for γ-herpesvirus load persistence and/or reactivation. We evaluated this hypothesis by investigating the levels of Epstein-Barr virus (EBV)- and Kaposi sarcoma-associated herpesvirus (KSHV)-DNA levels in the peripheral blood of 22 HIV-1-associated lymphoma patients during ASCT, highlighting their relationship with γ-herpesvirus lymphoma status, immunological parameters, and clinical events. EBV-DNA was detected in the pre-treatment plasma and peripheral blood mononuclear cells (PBMCs) of 12 (median 12,135 copies/mL) and 18 patients (median 417 copies/10(6) PBMCs), respectively; the values in the two compartments were correlated (r = 0.77, p = 0.0001). Only EBV-positive lymphomas showed detectable levels of plasma EBV-DNA. After debulking chemotherapy, plasma EBV-DNA was associated with lymphoma chemosensitivity (p = 0.03) and a significant higher mortality risk by multivariate Cox analysis adjusted for EBV-lymphoma status (HR, 10.46, 95% CI, 1.11-98.32, p = 0.04). After infusion, EBV-DNA was detectable in five EBV-positive lymphoma patients who died within six months. KSHV-DNA load was positive in only one patient, who died from primary effusion lymphoma. Fluctuations in levels of KSHV-DNA reflected the patient's therapy and evolution of his underlying lymphoma. Other γ-herpesvirus-associated malignancies, such as multicentric Castleman disease and Kaposi sarcoma, or end-organ complications after salvage treatment were not found. Overall, these findings suggest a prognostic and predictive value of EBV-DNA and KSHV-DNA, the monitoring of which could be a simple, complementary tool for the management of γ-herpesvirus-positive lymphomas in HIV-1 patients submitted to ASCT. PMID:25668032

  13. [A CASE OF ADVANCED BLADDER NEUROENDOCRINE CARCINOMA (SMALL CELL CARCINOMA) SIGNIFICANTLY IMPROVED BY LOW DOSE OF ORAL TEGAFUR-URACIL].

    PubMed

    Nomi, Hayahito; Takahara, Kiyoshi; Minami, Koichiro; Maenosono, Ryoichi; Matsunaga, Tomohisa; Yoshikawa, Yuki; Tsujino, Takuya; Hirano, Hajime; Inamoto, Teruo; Yamamoto, Ikuhisa; Tsuji, Motomu; Kiyama, Satoshi; Azuma, Haruhito

    2015-10-01

    A 81-old-woman underwent a transurethral resection of bladder tumor (TURBT) at a nearby hospital in April 2011. The diagnosis was invasive urothelial carcinoma, G3 with a component of bladder small cell carcinoma, T1 or more. She was recommended to visit our hospital for combined modality therapy of bladder cancer, but she refused the treatment for over one year. In May 2012, she came to our hospital with the chief complaint of pain at urination. Cystoscopy revealed non-papillary sessile tumor in the top of the bladder, and CT scan demonstrated the presence of the right obturator lymph nodes swollen up to 1.2 cm in size. The second TURBT was performed and the diagnosis was bladder small cell carcinoma (pT3N2M0) according to urothelial cancer guidelines of the Japanese Urological Association (JUA). Because she strongly refused hospitalization anymore, we started daily oral intake of low dose Tegafur-Uracil (100 mg) for the treatment. After one month, the serum Neuron-Specific Enolase (NSE; tumor maker of small cell cancer) level was elevated to 27.6 ng/ml and the right obturator lymph node was enlarged up to 1.9 cm. Therefore, the Trgafur-Uracil dose was increased to 200 mg daily. After then, the serum NSE level was decreased to 15.5 ng/ml following reduction in size of the obturator lymph nodes with partial response in December 2013. After two years of follow-up period, her regular urine test showed normal findings, and no apparent recurrence was detected on urinary bladder with MRI and Cystoscopy. This is a case of advanced bladder small cell carcinoma significantly improved by oral administration of Tegafur-Uracil 200 mg/day for over 2 years. PMID:26717786

  14. Neutropenia and Neutropenic Complications in ABVD Chemotherapy for Hodgkin Lymphoma

    PubMed Central

    Vakkalanka, Bhanu; Link, Brian K.

    2011-01-01

    A combination of Adriamycin (a.k.a. Doxorubicin), Bleomycin, Vinblastine, and Dacarbazine (ABVD) is the most commonly used chemotherapy regime for Hodgkin lymphoma. This highly effective treatment is associated with a significant risk of neutropenia. Various strategies are adopted to counter this commonly encountered problem, including dose modification, use of colony stimulating factors, and prophylactic or therapeutic use of antibiotics. Data to support these approaches is somewhat controversial, and in keeping with the paucity of definitive evidence, there is a wide disparity in the management of neutropenia in patients receiving ABVD chemotherapy. This paper summarizes the evidence for managing ABVD-related neutropenia during the treatment of Hodgkin lymphoma. PMID:21687649

  15. [Mobilization and collection of hematopoietic stem cells in children with different neoplastic diseases for autotransplantation to support high dose chemotherapy (single centre experience)].

    PubMed

    Goździk, Jolanta; Czogała, Wojciech; Skoczeń, Szymon; Krasowska-Kwiecień, Aleksandra; Wiecha, Oktawiusz; Stec, Małgorzata; Czogała, Małgorzata

    2011-01-01

    Currently, granulocyte colony stimulating factor (G-CSF) alone or in combination with myelosuppresive chemotherapy remain the standards of CD34+ cells mobilization allows the safe and successful collection of adequate peripheral blood stem cells (PBSC) for autologous transplantation. However, in up to 30% of patients mobilization of PBSC is ineffective. This report presents our experience in mobilization and collection of peripheral blood stem cells in 82 children with different proliferative disease. In mobilization G-CSF was administered alone in steady state (56 patients, pts) or in combination with myelosuppresive chemotherapy (26 pts). The CD34+ cell count at least 10 cells/ml was required to start apheresis procedure, which was repeated, if needed, during following 1-4 days until collection of at least 2 (optimally 3) x106 CD34+ cells/kg b.w. of recipient was obtained. Three pts in each group (3/ 56 and 3/26) failed the first course of mobilization. The median number of CD34+ cells mobilized was 4.8 (0.5-15) x106/kg b.w. The minimal and optimal number of CD34+ cells for transplantation was achieved in 85% and 61% of patients in the G-CSF + chemotherapy group and in 84% and 54% in the G-CSF group, respectively. The efficacy of presented mobilization arms in our group was similar. However, the incidence of infection and total hospitalization time during mobilization were higher in chemotherapy + G-CSF group. PMID:21853671

  16. Impact of high-dose chemotherapy and autologous transplantation as first-line therapy on the survival of high-risk diffuse large B cell lymphoma patients: a single-center study in Japan.

    PubMed

    Inano, Shojiro; Iwasaki, Makoto; Iwamoto, Yoshihiro; Sueki, Yuki; Fukunaga, Akiko; Yanagita, Soshi; Arima, Nobuyoshi

    2014-02-01

    High-dose chemotherapy (HDT), together with autologous stem cell transplantation (ASCT), plays an important role in the treatment of diffuse large B cell lymphoma (DLBCL), especially as second-line therapy. However, its significance in up-front settings remains to be elucidated. In our institute, patients with DLBCL in both the high-intermediate and high international prognostic index (IPI) groups initially underwent CHOP/R-CHOP treatment followed by HDT/ASCT at upfront settings between 2002 and 2011. We retrospectively analyzed 25 patients who were all treated with upfront HDT/ASCT. We excluded one patient who failed to undergo transplantation because of primary refractory disease from the analysis. The median follow-up was 77 months (range 17-110 months). Five-year overall survival (OS) and progression-free survival (PFS) were 91.7 and 79.2 %, respectively, which were higher than the equivalents in previous studies. The OS and PFS in the high-risk group were lower than those in the high-intermediate group. Treatment-related mortalities or fatal complication were not observed. Our results confirm that HDT/ASCT for high-risk aggressive lymphoma is a feasible and promising therapy, but patients with high IPI continued to have poor prognoses; improvements in treatment strategy are clearly needed. Since HDT/ASCT is an aggressive treatment option associated with long-term complications, we need to identify patient groups that will gain the maximum benefit from HDT/ASCT in the upfront setting. PMID:24338743

  17. High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation as Adjuvant Treatment in High-Risk Breast Cancer: Data from the European Group for Blood and Marrow Transplantation Registry.

    PubMed

    Martino, Massimo; Lanza, Francesco; Pavesi, Lorenzo; Öztürk, Mustafa; Blaise, Didier; Leno Núñez, Rubén; Schouten, Harry C; Bosi, Alberto; De Giorgi, Ugo; Generali, Daniele; Rosti, Giovanni; Necchi, Andrea; Ravelli, Andrea; Bengala, Carmelo; Badoglio, Manuela; Pedrazzoli, Paolo; Bregni, Marco

    2016-03-01

    The aim of this retrospective study was to assess toxicity and efficacy of adjuvant high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation (AHSCT) in 583 high-risk breast cancer (BC) patients (>3 positive nodes) who were transplanted between 1995 and 2005 in Europe. All patients received surgery before transplant, and 55 patients (9.5%) received neoadjuvant treatment before surgery. Median age was 47.1 years, 57.3% of patients were premenopausal at treatment, 56.5% had endocrine-responsive tumors, 19.5% had a human epidermal growth factor receptor 2 (HER2)-negative tumor, and 72.4% had ≥10 positive lymph nodes at surgery. Seventy-nine percent received a single HDC procedure. Overall transplant-related mortality was 1.9%, at .9% between 2001 and 2005, whereas secondary tumor-related mortality was .9%. With a median follow-up of 120 months, overall survival and disease-free survival rates at 5 and 10 years in the whole population were 75% and 64% and 58% and 44%, respectively. Subgroup analysis demonstrated that rates of overall survival were significantly better in patients with endocrine-responsive tumors, <10 positive lymph nodes, and smaller tumor size. HER2 status did not affect survival probability. Adjuvant HDC with AHSCT has a low mortality rate and provides impressive long-term survival rates in patients with high-risk BC. Our results suggest that this treatment modality should be considered in selected high-risk BC patients and further investigated in clinical trials. PMID:26723932

  18. Phase I trial of split-dose induction docetaxel, cisplatin, and 5-fluorouracil (TPF) chemotherapy followed by curative surgery combined with postoperative radiotherapy in patients with locally advanced oral and oropharyngeal squamous cell cancer (TISOC-1)

    PubMed Central

    2012-01-01

    Background Induction chemotherapy (ICT) with docetaxel, cisplatin and fluorouracil (TPF) followed by radiotherapy is an effective treatment option for unresectable locally advanced head and neck cancer. This phase I study was designed to investigate the safety and tolerability of a split-dose TPF ICT regimen prior to surgery for locally advanced resectable oral and oropharyngeal cancer. Methods Patients received TPF split on two dosages on day 1 and 8 per cycle for one or three 3-week cycles prior to surgery and postoperative radiotherapy or radiochemotherapy. Docetaxel was escalated in two dose levels, 40 mg/m2 (DL 0) and 30 mg/m2 (DL −1), plus 40 mg/m2 cisplatin and 2000 mg/m2 fluorouracil per week using a 3 +3 dose escalation algorithm. Results Eighteen patients were enrolled and were eligible for toxicity and response. A maximum tolerated dose of 30 mg/m2 docetaxel per week was reached. The most common grade 3+ adverse event was neutropenia during ICT in 10 patients. Surgery reached R0 resection in all cases. Nine patients (50%) showed complete pathologic regression. Conclusions A split-dose regime of TPF prior to surgery is feasible, tolerated and merits additional investigation in a phase II study with a dose of 30 mg/m docetaxel per week. Trial registration number NCT01108042 (ClinicalTrials.gov Identifier) PMID:23083061

  19. Sequential multiagent chemotherapy is not superior to high-dose cytarabine alone as postremission intensification therapy for acute myeloid leukemia in adults under 60 years of age: Cancer and Leukemia Group B Study 9222

    PubMed Central

    Moore, Joseph O.; George, Stephen L.; Dodge, Richard K.; Amrein, Philip C.; Powell, Bayard L.; Kolitz, Jonathan E.; Baer, Maria R.; Davey, Frederick R.; Bloomfield, Clara D.; Larson, Richard A.; Schiffer, Charles A.

    2005-01-01

    The Cancer and Leukemia Group B (CALGB) study 9222 tested the hypothesis that treatment intensification of acute myeloid leukemia (AML) in first remission with multiple chemotherapy agents is superior to high-dose cytarabine (HiDAC) alone. We enrolled 474 patients younger than 60 years old with untreated de novo AML. Daunorubicin and cytarabine resulted in complete remission (CR) in 342 patients (72%), and 309 of these patients were randomized to receive one of 2 different intensification regimens. The first regimen consisted of 3 courses of HiDAC. The second regimen consisted of one course of HiDAC, a second course with etoposide and cyclophosphamide, and a third course with diaziquone and mitoxantrone. After a median follow-up time of 8.3 years, the median survival for all randomized patients was 2.8 years (95% CI, 1.9-6.8 years). There was no difference in disease-free survival (DFS) between the 2 regimens (P = .66). The median DFS was 1.1 years (95% CI, 0.9-1.7 years) for patients receiving HiDAC and 1.0 year (95% CI, 0.9-1.3 years) for those receiving multiagent chemotherapy. Cytogenetics was the only pretreatment characteristic prognostic for DFS, but there was no evidence of a differential treatment effect within cytogenetic risk groups. Toxicity was greater with multiagent chemotherapy. These 2 postremission regimens produced similar outcomes. PMID:15572587

  20. Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

    PubMed Central

    Selle, F.; Gligorov, J.; Richard, S.; Khalil, A.; Alexandre, I.; Avenin, D.; Provent, S.; Soares, D.G.; Lotz, J.P.

    2014-01-01

    Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis. PMID:25493378

  1. Incidence of and significant risk factors for aminoglycoside-associated nephrotoxicity in patients dosed by using individualized pharmacokinetic monitoring.

    PubMed

    Bertino, J S; Booker, L A; Franck, P A; Jenkins, P L; Franck, K R; Nafziger, A N

    1993-01-01

    Incidence of and risk factors for aminoglycoside-associated nephrotoxicity (AAN) were evaluated in 1489 patients prospectively monitored with individualized pharmacokinetic monitoring (IPM). Incidence of AAN was 7.9% with individual (univariate) risk factors including advanced age, decreased albumin, poor nutritional status, pneumonia, concurrent furosemide, amphotericin B, vancomycin, cephalosporin, or piperacillin, intensive care unit treatment, leukemia, rapidly fatal illness, liver or renal disease, reduced aminoglycoside clearance, elevated initial steady-state trough concentration (Cminss), volume of distribution or half-life, duration of therapy, total dose, fever, male gender, shock, pleural effusion, and ascites. Multiple logistic regression revealed that Cminss, concurrent clindamycin, vancomycin, piperacillin, or cephalosporin, ascites, advanced age, male gender, decreased albumin, duration of therapy, and leukemia were significant independent risk factors for AAN. Positive predictive value of the model was 30.8%; negative predictive value was 91.7%. No identifiable risk factor alone or in combination was of sufficient sensitivity to reliably predict AAN, but use of IPM may lower the incidence of AAN. PMID:8418164

  2. Understanding Chemotherapy

    MedlinePlus

    ... you may get chemotherapy before a peripheral blood stem cell transplant. Fill this section in with your doctor or nurse. I am getting chemo ... can be given in these forms: An IV (intravenously) A shot (injection) into a muscle or other part of your body A pill ...

  3. Hospice management of patients receiving cytotoxic chemotherapy: problems and opportunities.

    PubMed

    Hicks, F; Corcoran, G

    1993-12-01

    In Britain, the specialty of palliative medicine continues to develop, encouraging the referral of patients early in the palliative phase of their illness. This had led to an increased number of patients receiving palliative chemotherapy and hospice care concurrently, posing special problems to the professionals involved. In this retrospective study, 52 patients were identified who received chemotherapy and hospice care simultaneously. Case notes were reviewed to reveal problems arising from sharing the duty of care. The poor quality of communication between professionals, perhaps reflecting a limited understanding of the various roles in patient care, we found to cause significant difficulties. The duration and discontinuation of cytotoxic therapy seems to be a particularly difficult matter. Hospice admission often signalled the end of this treatment. In a third of the patients, no decision was taken to stop chemotherapy despite the last dose being an average of just 1 week before death. The value of chemotherapy for patients who are too ill to return home is questioned. Seven patients were diagnosed as suffering from chemotherapy-induced sepsis and neutropenia either by hospice inpatient or home care teams, and were admitted to their acute centres accordingly. Most patients who died during the study period received terminal care in the hospice. Suggestions are made on improving professional education and communication, including the use of a 'chemotherapy card'. PMID:7505105

  4. Impact of High-Dose Chemotherapy on the Ability to Deliver Subsequent Local-Regional Radiotherapy for Breast Cancer: Analysis of Cancer and Leukemia Group B Protocol 9082

    SciTech Connect

    Marks, Lawrence B.; Cirrincione, Constance M.S.; Fitzgerald, Thomas J.; Laurie, Frances; Glicksman, Arvin S.; Vredenburgh, James; Prosnitz, Leonard R.; Shpall, Elizabeth J.; Crump, Michael; Richardson, Paul G.; Schuster, Michael W.; Ma Jinli; Peterson, Bercedis L.; Norton, Larry; Seagren, Steven

    2010-04-15

    Purpose: To report, from Cancer and Leukemia Group B Protocol 9082, the impact of high-dose cyclophosphamide, cisplatin, and BCNU (HD-CPB) vs. intermediate-dose CPB (ID-CPB) on the ability to start and complete the planned course of local-regional radiotherapy (RT) for women with breast cancer involving >=10 axillary nodes. Methods and Materials: From 1991 to 1998, 785 patients were randomized. The HD-CPB and ID-CPB arms were balanced regarding patient characteristics. The HD-CPB and ID-CPB arms were compared on the probability of RT initiation, interruption, modification, or incompleteness. The impact of clinical variables and interactions between variables were also assessed. Results: Radiotherapy was initiated in 82% (325 of 394) of HD-CPB vs. 92% (360 of 391) of ID-CPB patients (p = 0.001). On multivariate analyses, RT was less likely given to patients who were randomized to HD treatment (odds ratio [OR] = 0 .38, p < 0.001), older (p = 0.005), African American (p = 0.003), postmastectomy (p = 0.02), or estrogen receptor positive (p = 0.03). High-dose treatment had a higher rate of RT interruption (21% vs. 12%, p = 0.001, OR = 2.05), modification (29% vs. 14%, p = 0.001, OR = 2.46), and early termination of RT (9% vs. 2%, p = 0.0001, OR = 5.35), compared with ID. Conclusion: Treatment arm significantly related to initiation, interruption, modification, and early termination of RT. Patients randomized to HD-CPB were less likely to initiate RT, and of those who did, they were more likely to have RT interrupted, modified, and terminated earlier than those randomized to ID-CPB. The observed lower incidence of RT usage in African Americans vs. non-African Americans warrants further study.

  5. Dose-dense sequential adjuvant chemotherapy followed, as indicated, by trastuzumab for one year in patients with early breast cancer: first report at 5-year median follow-up of a Hellenic Cooperative Oncology Group randomized phase III trial

    PubMed Central

    2014-01-01

    Background Dose-dense sequential chemotherapy including anthracyclines and taxanes has been established in the adjuvant setting of high-risk operable breast cancer. However, the preferable taxane and optimal schedule of administration in a dose-dense regimen have not been defined yet. Methods From July 2005 to November 2008, 1001 patients (990 eligible) were randomized to receive, every 2 weeks, 3 cycles of epirubicin 110 mg/m2 followed by 3 cycles of paclitaxel 200 mg/m2 followed by 3 cycles of intensified CMF (Arm A; 333 patients), or 3 cycles of epirubicin followed by 3 cycles of CMF, as in Arm A, followed 3 weeks later by 9 weekly cycles of docetaxel 35 mg/m2 (Arm B; 331), or 9 weekly cycles of paclitaxel 80 mg/m2 (Arm C; 326). Trastuzumab was administered for one year to HER2-positive patients post-radiation. Results At a median follow-up of 60.5 months, the 3-year disease-free survival (DFS) rate was 86%, 90% and 88%, for Arms A, B and C, respectively, while the 3-year overall survival (OS) rate was 96% in all arms. No differences were found in DFS or OS between the combined B and C Arms versus Arm A (DFS: HR = 0.81, 95% CI: 0.59-1.11, P = 0.20; OS: HR = 0.84, 95% CI: 0.55-1.30, P = 0.43). Among the 255 patients who received trastuzumab, 189 patients (74%) completed 1 year of treatment uneventfully. In all arms, the most frequently reported severe adverse events were neutropenia (30% vs. 27% vs. 26%) and leucopenia (12% vs. 13% vs. 12%), while febrile neutropenia occurred in fifty-one patients (6% vs. 4% vs. 5%). Patients in Arm A experienced more often severe pain (P = 0.002), neurological complications (P = 0.004) and allergic reactions (P = 0.004), while patients in Arm B suffered more often from severe skin reactions (P = 0.020). Conclusions No significant differences in survival between the regimens were found in the present phase III trial. Taxane scheduling influenced the type of severe toxicities. HER2

  6. High Dose Atorvastatin Associated with Increased Risk of Significant Hepatotoxicity in Comparison to Simvastatin in UK GPRD Cohort

    PubMed Central

    Clarke, Alan T.; Johnson, Paul C. D.; Hall, Gillian C.; Ford, Ian; Mills, Peter R.

    2016-01-01

    Background & Aims Occasional risk of serious liver dysfunction and autoimmune hepatitis during atorvastatin therapy has been reported. We compared the risk of hepatotoxicity in atorvastatin relative to simvastatin treatment. Methods The UK GPRD identified patients with a first prescription for simvastatin [164,407] or atorvastatin [76,411] between 1997 and 2006, but with no prior record of liver disease, alcohol-related diagnosis, or liver dysfunction. Incident liver dysfunction in the following six months was identified by biochemical value and compared between statin groups by Cox regression model adjusting for age, sex, year treatment started, dose, alcohol consumption, smoking, body mass index and comorbid conditions. Results Moderate to severe hepatotoxicity [bilirubin >60μmol/L, AST or ALT >200U/L or alkaline phosphatase >1200U/L] developed in 71 patients on atorvastatin versus 101 on simvastatin. Adjusted hazard ratio [AHR] for all atorvastatin relative to simvastatin was 1.9 [95% confidence interval 1.4–2.6]. High dose was classified as 40–80mg daily and low dose 10–20mg daily. Hepatotoxicity occurred in 0.44% of 4075 patients on high dose atorvastatin [HDA], 0.07% of 72,336 on low dose atorvastatin [LDA], 0.09% of 44,675 on high dose simvastatin [HDS] and 0.05% of 119,732 on low dose simvastatin [LDS]. AHRs compared to LDS were 7.3 [4.2–12.7] for HDA, 1.4 [0.9–2.0] for LDA and 1.5 [1.0–2.2] for HDS. Conclusions The risk of hepatotoxicity was increased in the first six months of atorvastatin compared to simvastatin treatment, with the greatest difference between high dose atorvastatin and low dose simvastatin. The numbers of events in the analyses were small. PMID:26983033

  7. Impact of Drug Therapy, Radiation Dose, and Dose Rate on Renal Toxicity Following Bone Marrow Transplantation

    SciTech Connect

    Cheng, Jonathan C.; Schultheiss, Timothy E. Wong, Jeffrey Y.C.

    2008-08-01

    Purpose: To demonstrate a radiation dose response and to determine the dosimetric and chemotherapeutic factors that influence the incidence of late renal toxicity following total body irradiation (TBI). Methods and Materials: A comprehensive retrospective review was performed of articles reporting late renal toxicity, along with renal dose, fractionation, dose rate, chemotherapy regimens, and potential nephrotoxic agents. In the final analysis, 12 articles (n = 1,108 patients), consisting of 24 distinct TBI/chemotherapy conditioning regimens were included. Regimens were divided into three subgroups: adults (age {>=}18 years), children (age <18 years), and mixed population (both adults and children). Multivariate logistic regression was performed to identify dosimetric and chemotherapeutic factors significantly associated with late renal complications. Results: Individual analysis was performed on each population subgroup. For the purely adult population, the only significant variable was total dose. For the mixed population, the significant variables included total dose, dose rate, and the use of fludarabine. For the pediatric population, only the use of cyclosporin or teniposide was significant; no dose response was noted. A logistic model was generated with the exclusion of the pediatric population because of its lack of dose response. This model yielded the following significant variables: total dose, dose rate, and number of fractions. Conclusion: A dose response for renal damage after TBI was identified. Fractionation and low dose rates are factors to consider when delivering TBI to patients undergoing bone marrow transplantation. Drug therapy also has a major impact on kidney function and can modify the dose-response function.

  8. Phase I Study of Concurrent High-Dose Three-Dimensional Conformal Radiotherapy With Chemotherapy Using Cisplatin and Vinorelbine for Unresectable Stage III Non-Small-Cell Lung Cancer

    SciTech Connect

    Sekine, Ikuo; Sumi, Minako; Ito, Yoshinori; Horinouchi, Hidehito; Nokihara, Hiroshi; Yamamoto, Noboru; Kunitoh, Hideo; Ohe, Yuichiro; Kubota, Kaoru; Tamura, Tomohide

    2012-02-01

    Purpose: To determine the maximum tolerated dose in concurrent three-dimensional conformal radiotherapy (3D-CRT) with chemotherapy for unresectable Stage III non-small-cell lung cancer (NSCLC). Patients and Methods: Eligible patients with unresectable Stage III NSCLC, age {>=}20 years, performance status 0-1, percent of volume of normal lung receiving 20 GY or more (V{sub 20}) {<=}30% received three to four cycles of cisplatin (80 mg/m{sup 2} Day 1) and vinorelbine (20 mg/m{sup 2} Days 1 and 8) repeated every 4 weeks. The doses of 3D-CRT were 66 Gy, 72 Gy, and 78 Gy at dose levels 1 to 3, respectively. Results: Of the 17, 16, and 24 patients assessed for eligibility, 13 (76%), 12 (75%), and 6 (25%) were enrolled at dose levels 1 to 3, respectively. The main reasons for exclusion were V{sub 20} >30% (n = 10) and overdose to the esophagus (n = 8) and brachial plexus (n = 2). There were 26 men and 5 women, with a median age of 60 years (range, 41-75). The full planned dose of radiotherapy could be administered to all the patients. Grade 3-4 neutropenia and febrile neutropenia were noted in 24 (77%) and 5 (16%) of the 31 patients, respectively. Grade 4 infection, Grade 3 esophagitis, and Grade 3 pulmonary toxicity were noted in 1 patient, 2 patients, and 1 patient, respectively. The dose-limiting toxicity was noted in 17% of the patients at each dose level. The median survival and 3-year and 4-year survival rates were 41.9 months, 72.3%, and 49.2%, respectively. Conclusions: 72 Gy was the maximum dose that could be achieved in most patients, given the predetermined normal tissue constraints.

  9. Phase I North Central Cancer Treatment Group Trial-N9923 of escalating doses of twice-daily thoracic radiation therapy with amifostine and with alternating chemotherapy in limited stage small-cell lung cancer

    SciTech Connect

    Garces, Yolanda I. . E-mail: garces.yolanda@Mayo.edu; Okuno, Scott H.; Schild, Steven E.; Mandrekar, Sumithra J.; Bot, Brian M.; Martens, John M.; Wender, Donald B.; Soori, Gamini S.; Moore, Dennis F.; Kozelsky, Timothy F.; Jett, James R.

    2007-03-15

    Purpose: The primary goal was to identify the maximum tolerable dose (MTD) of thoracic radiation therapy (TRT) that can be given with chemotherapy and amifostine for patients with limited-stage small-cell lung cancer (LSCLC). Methods and Materials: Treatment began with two cycles of topotecan (1 mg/m{sup 2}) Days 1 to 5 and paclitaxel (175 mg/m{sup 2}) Day 5 (every 3 weeks) given before and after TRT. The TRT began at 6 weeks. The TRT was given in 120 cGy fractions b.i.d. and the dose escalation (from 4,800 cGy, dose level 1, to 6,600 cGy, dose level 4) followed the standard 'cohorts of 3' design. The etoposide (E) (50 mg/day) and cisplatin (C) (3 mg/m{sup 2}) were given i.v. before the morning TRT and amifostine (500 mg/day) was given before the afternoon RT. This was followed by prophylactic cranial irradiation (PCI). The dose-limiting toxicities (DLTs) were defined as Grade {>=}4 hematologic, febrile neutropenia, esophagitis, or other nonhematologic toxicity, Grade {>=}3 dyspnea, or Grade {>=}2 pneumonitis. Results: Fifteen patients were evaluable for the Phase I portion of the trial. No DLTs were seen at dose levels 1 and 2. Two patients on dose level 4 experienced DLTs: 1 patient had a Grade 4 pneumonitis, dyspnea, fatigue, hypokalemia, and anorexia, and 1 patient had a Grade 5 hypoxia attributable to TRT. One of 6 patients on dose level 3 had a DLT, Grade 3 esophagitis. The Grade {>=}3 toxicities seen in at least 10% of patients during TRT were esophagitis (53%), leukopenia (33%), dehydration (20%), neutropenia (13%), and fatigue (13%). The median survival was 14.5 months. Conclusion: The MTD of b.i.d. TRT was 6000 cGy (120 cGy b.i.d.) with EP and amifostine.

  10. Induction chemotherapy in metastatic neuroblastoma--does dose influence response? A critical review of published data standards, options and recommendations (SOR) project of the National Federation of French Cancer Centres (FNCLCC).

    PubMed

    Pinkerton, C R; Blanc Vincent, M P; Bergeron, C; Fervers, B; Philip, T

    2000-09-01

    The purpose of this study was to determine, from a review of published data, whether in stage 4 neuroblastoma in children over 1 year of age, the dose or scheduling of induction chemotherapy influenced the response rate in distant metastases. Publications relating to induction chemotherapy since the introduction of cisplatin/epipodophyllotoxin combinations were identified using Medline, Current Contents and personal reference lists. Thirteen publications were identified which described 17 regimens involving 948 children. The doses and the scheduling of the various regimens were compared with a standard regimen OPEC (vincristine, cisplatin, teniposide, cyclophosphamide). These were correlated with the reported response rates in the bone marrow. Due to a lack of standardisation in the nature of restaging investigations, timing of restaging and definitions of response it was difficult to compare all studies. The complete response rate at distant metastases ranged from less than 40% to over 90%. For individual drugs; the comparative doses given in each course ranged up to 4.2 g/m(2) for cyclophosphamide, 280 mg/m(2) for cisplatin, 600 mg/m(2) for etoposide and 4.5 mg/m(2) for vincristine. There was no evidence of any positive correlation between response rate in the marrow and either the dose of any individual drug or the schedule used. In contrast to a previous study which included a number of older studies where disease assessment was even more variable, this analysis has failed to show any justification for the routine use of very intensive induction regimens in this disease. Such an approach should only be taken in the context of randomised trials in which timing and methods of reassessment can be standardised. Until such studies demonstrate superiority either in terms of response rate or progression-free survival lower morbidity regimens should remain the standard therapy. PMID:10974629

  11. Extended continuous infusion low-dose recombinant interleukin-2 in advanced cancer: prolonged immunomodulation without significant toxicity.

    PubMed

    Caligiuri, M A; Murray, C; Soiffer, R J; Klumpp, T R; Seiden, M; Cochran, K; Cameron, C; Ish, C; Buchanan, L; Perillo, D

    1991-12-01

    In previous clinical trials, recombinant interleukin-2 (rIL-2) has been infused at high doses over short periods of time to generate lymphokine-activated killer (LAK) cells in vivo. These trials have been limited by severe toxicities, and the immunologic effects of rIL-2 have been transient. The present study was designed to assess the toxicity and immunologic effects of prolonged administration of low doses of rIL-2. In this phase I study, patients with advanced cancer were scheduled to receive intravenous (IV) infusion of rIL-2 without interruption for 3 months in an outpatient setting. Twenty-one patients received rIL-2 at doses ranging from 0.5 x 10(5) to 6.0 x 10(5) U/m2/d. Treatment was extremely well tolerated, and no patient experienced grade 3 or grade 4 toxicity. The lowest dose level (0.5 x 10(5) U/m2/d) did not have demonstrable immunologic activity. At doses of 1.5 x 10(5) and 4.5 x 10(5) U/m2/d, rIL-2 infusion resulted in the specific expansion of natural-killer (NK) cells (sixfold and ninefold increases, respectively, at these two dose levels) without any changes in B cells, T cells, neutrophils, or monocytes. Grade 2 toxicity was observed at the dose of 6.0 x 10(5) U/m2/d, as three patients required interruption of therapy and two patients who completed therapy developed transient hypothyroidism. In patients with increased NK cells, enhancement of non-major histocompatibility complex (MHC)-restricted cytotoxicity and increased generation of LAK cells in vitro were also demonstrated. Therapy with low-dose rIL-2 can be given safely in an uninterrupted fashion for prolonged periods of time in an outpatient setting. This results in selective expansion of NK cells in vivo with minimal toxicity. Further investigation of this schedule for immunomodulation in vivo should be pursued in phase II studies of both malignant and immunodeficient disease states. PMID:1960552

  12. A quantitative sensory analysis of peripheral neuropathy in colorectal cancer and its exacerbation by oxaliplatin chemotherapy.

    PubMed

    de Carvalho Barbosa, Mariana; Kosturakis, Alyssa K; Eng, Cathy; Wendelschafer-Crabb, Gwen; Kennedy, William R; Simone, Donald A; Wang, Xin S; Cleeland, Charles S; Dougherty, Patrick M

    2014-11-01

    Peripheral neuropathy caused by cytotoxic chemotherapy, especially platins and taxanes, is a widespread problem among cancer survivors that is likely to continue to expand in the future. However, little work to date has focused on understanding this challenge. The goal in this study was to determine the impact of colorectal cancer and cumulative chemotherapeutic dose on sensory function to gain mechanistic insight into the subtypes of primary afferent fibers damaged by chemotherapy. Patients with colorectal cancer underwent quantitative sensory testing before and then prior to each cycle of oxaliplatin. These data were compared with those from 47 age- and sex-matched healthy volunteers. Patients showed significant subclinical deficits in sensory function before any therapy compared with healthy volunteers, and they became more pronounced in patients who received chemotherapy. Sensory modalities that involved large Aβ myelinated fibers and unmyelinated C fibers were most affected by chemotherapy, whereas sensory modalities conveyed by thinly myelinated Aδ fibers were less sensitive to chemotherapy. Patients with baseline sensory deficits went on to develop more symptom complaints during chemotherapy than those who had no baseline deficit. Patients who were tested again 6 to 12 months after chemotherapy presented with the most numbness and pain and also the most pronounced sensory deficits. Our results illuminate a mechanistic connection between the pattern of effects on sensory function and the nerve fiber types that appear to be most vulnerable to chemotherapy-induced toxicity, with implications for how to focus future work to ameloirate risks of peripheral neuropathy. PMID:25183707

  13. Predictors of tolerance to chemotherapy in older cancer patients: a prospective pilot study.

    PubMed

    Extermann, M; Chen, H; Cantor, A B; Corcoran, M B; Meyer, J; Grendys, E; Cavanaugh, D; Antonek, S; Camarata, A; Haley, W E; Balducci, L

    2002-07-01

    Few data are available to help predict which older cancer patient is at risk of developing chemotherapy-related toxicity. This study was a pilot for a project designing a predictive risk score. Chemotherapy patients aged 70 years and older were prospectively enrolled. Chemotherapies were adjusted for their published toxicity. 60 patients were enrolled, 59 were evaluable. Mean dose-intensity was 90.3%, range 33.3-129.0%. 47% of the patients experienced grade 4 haematological and/or grade 3-4 non-haematological toxicity. Published toxicity (MAX2), diastolic blood pressure, marrow invasion and lactate dehydrogenase (LDH) were all associated with toxicity (P<0.1); Body Mass Index, previous chemotherapy, red blood cells, platelets, polymedication with dose-intensity; and polymedication with FACT-G change. After adjustment for the published toxicity, the variables retained their significance, except for LDH and polymedication (for dose-intensity). Although the size of this pilot study imposes a cautious interpretation, patient-related and chemotherapy-related variables correlated independently with toxicity. Designing a composite predictive score to use in assessing the toxicity of multiple chemotherapy regimens therefore appears to be a valid undertaking. PMID:12110492

  14. Pulmonary Toxicity in Stage III Non-Small Cell Lung Cancer Patients Treated With High-Dose (74 Gy) 3-Dimensional Conformal Thoracic Radiotherapy and Concurrent Chemotherapy Following Induction Chemotherapy: A Secondary Analysis of Cancer and Leukemia Group B (CALGB) Trial 30105

    SciTech Connect

    Salama, Joseph K.; Stinchcombe, Thomas E.; Gu Lin; Wang Xiaofei; Morano, Karen; Bogart, Jeffrey A.; Crawford, Jeffrey C.; Socinski, Mark A.; Blackstock, A. William; Vokes, Everett E.

    2011-11-15

    Purpose: Cancer and Leukemia Group B (CALGB) 30105 tested two different concurrent chemoradiotherapy platforms with high-dose (74 Gy) three-dimensional conformal radiotherapy (3D-CRT) after two cycles of induction chemotherapy for Stage IIIA/IIIB non-small cell lung cancer (NSCLC) patients to determine if either could achieve a primary endpoint of >18-month median survival. Final results of 30105 demonstrated that induction carboplatin and gemcitabine and concurrent gemcitabine 3D-CRT was not feasible because of treatment-related toxicity. However, induction and concurrent carboplatin/paclitaxel with 74 Gy 3D-CRT had a median survival of 24 months, and is the basis for the experimental arm in CALGB 30610/RTOG 0617/N0628. We conducted a secondary analysis of all patients to determine predictors of treatment-related pulmonary toxicity. Methods and Materials: Patient, tumor, and treatment-related variables were analyzed to determine their relation with treatment-related pulmonary toxicity. Results: Older age, higher N stage, larger planning target volume (PTV)1, smaller total lung volume/PTV1 ratio, larger V20, and larger mean lung dose were associated with increasing pulmonary toxicity on univariate analysis. Multivariate analysis confirmed that V20 and nodal stage as well as treatment with concurrent gemcitabine were associated with treatment-related toxicity. A high-risk group comprising patients with N3 disease and V20 >38% was associated with 80% of Grades 3-5 pulmonary toxicity cases. Conclusions: Elevated V20 and N3 disease status are important predictors of treatment related pulmonary toxicity in patients treated with high-dose 3D-CRT and concurrent chemotherapy. Further studies may use these metrics in considering patients for these treatments.

  15. Addition of a third field significantly increases dose to the brachial plexus for patients undergoing tangential whole-breast therapy after lumpectomy

    SciTech Connect

    Stanic, Sinisa; Mathai, Mathew; Mayadev, Jyoti S.; Do, Ly V.; Purdy, James A.; Chen, Allen M.

    2012-07-01

    Our goal was to evaluate brachial plexus (BP) dose with and without the use of supraclavicular (SCL) irradiation in patients undergoing breast-conserving therapy with whole-breast radiation therapy (RT) after lumpectomy. Using the standardized Radiation Therapy Oncology Group (RTOG)-endorsed guidelines delineation, we contoured the BP for 10 postlumpectomy breast cancer patients. The radiation dose to the whole breast was 50.4 Gy using tangential fields in 1.8-Gy fractions, followed by a conedown to the operative bed using electrons (10 Gy). The prescription dose to the SCL field was 50.4 Gy, delivered to 3-cm depth. The mean BP volume was 14.5 {+-} 1.5 cm{sup 3}. With tangential fields alone, the median mean dose to the BP was 0.57 Gy, the median maximum dose was 1.93 Gy, and the irradiated volume of the BP receiving 40, 45, and 50 Gy was 0%. When the third (SCL field) was added, the dose to the BP was significantly increased (P = .01): the median mean dose to the BP was 40.60 Gy, and the median maximum dose was 52.22 Gy. With 3-field RT, the median irradiated volume of the BP receiving 40, 45, and 50 Gy was 83.5%, 68.5%, and 24.6%, respectively. The addition of the SCL field significantly increases dose to the BP. The possibility of increasing the risk of BP morbidity should be considered in the context of clinical decision making.

  16. MicroRNAs and Metabolites in Serum Change after Chemotherapy: Impact on Hematopoietic Stem and Progenitor Cells

    PubMed Central

    Jost, Edgar; Morin-Kensicki, Elizabeth; Goecke, Tamme W.; Bosio, Andreas; Rath, Björn; Brümmendorf, Tim H.; Bissels, Ute; Wagner, Wolfgang

    2015-01-01

    Hematopoietic regeneration after high dose chemotherapy necessitates activation of the stem cell pool. There is evidence that serum taken after chemotherapy comprises factors stimulating proliferation and self-renewal of CD34+ hematopoietic stem and progenitor cells (HSPCs) – however, the nature of these feedback signals is yet unclear. Here, we addressed the question if specific microRNAs (miRNAs) or metabolites are affected after high dose chemotherapy. Serum taken from the same patients before and after chemotherapy was supplemented for in vitro cultivation of HSPCs. Serum taken after chemotherapy significantly enhanced HSPC proliferation, better maintained a CD34+ immunophenotype, and stimulated colony forming units. Microarray analysis revealed that 23 miRNAs changed in serum after chemotherapy – particularly, miRNA-320c and miRNA-1275 were down-regulated whereas miRNA-3663-3p was up-regulated. miRNA-320c was exemplarily inhibited by an antagomiR, which seemed to increase proliferation. Metabolomic profiling demonstrated that 44 metabolites were less abundant, whereas three (including 2-hydroxybutyrate and taurocholenate sulphate) increased in serum upon chemotherapy. Nine of these metabolites were subsequently tested for effects on HSPCs in vitro, but none of them exerted a clear concentration dependent effect on proliferation, immunophenotype and colony forming unit formation. Taken together, serum profiles of miRNAs and metabolites changed after chemotherapy. Rather than individually, these factors may act in concert to recruit HSPCs into action for hematopoietic regeneration. PMID:26024523

  17. High-dose chemotherapy (HDCT) with auto-SCT in children with atypical teratoid/rhabdoid tumors (AT/RT): a report from the European Rhabdoid Registry (EU-RHAB).

    PubMed

    Benesch, M; Bartelheim, K; Fleischhack, G; Gruhn, B; Schlegel, P G; Witt, O; Stachel, K D; Hauch, H; Urban, C; Quehenberger, F; Massimino, M; Pietsch, T; Hasselblatt, M; Giangaspero, F; Kordes, U; Schneppenheim, R; Hauser, P; Klingebiel, T; Frühwald, M C

    2014-03-01

    A retrospective analysis of data from the European Rhabdoid Registry (EU-RHAB) was performed to describe the outcome of children with atypical teratoid/rhabdoid tumors (AT/RT) who underwent high-dose chemotherapy (HDCT) with auto-SCT. Nineteen patients (male, n=15; median age at diagnosis 21 months) were identified. Nine patients presented with metastatic disease at diagnosis. A partial or subtotal resection was achieved in 11, a total resection in five and a biopsy in three patients. Patients received a median of six chemotherapy cycles prior to HDCT. Additional radiotherapy was performed in 14 patients (first-line, n=9; following progression, n=5). Six patients underwent tandem auto-SCT. Disease status before HDCT was CR in six, PR in eight, stable disease in two and progressive disease (PD) in two patients (data missing, n=1). With a median follow-up of 16 months, 14 patients progressed. Estimated progression-free and OS at 2 years were 29% (±11%) and 50% (±12%), respectively. At last follow-up, eight patients were alive (first CR, n=4; second CR, n=2; PR, n=1; PD, n=1). Eleven patients died of PD. Median time-to-progression was 14 months. Selected patients with AT/RT might benefit from HDCT with radiotherapy. The definitive impact of this treatment modality has to be evaluated prospectively in a randomized trial. PMID:24419520

  18. MRI-Guided 3D Optimization Significantly Improves DVH Parameters of Pulsed-Dose-Rate Brachytherapy in Locally Advanced Cervical Cancer

    SciTech Connect

    Lindegaard, Jacob C. Tanderup, Kari; Nielsen, Soren Kynde; Haack, Soren; Gelineck, John

    2008-07-01

    Purpose: To compare dose-volume histogram parameters of standard Point A and magnetic resonance imaging-based three-dimensional optimized dose plans in 21 consecutive patients who underwent pulsed-dose-rate brachytherapy (PDR-BT) for locally advanced cervical cancer. Methods and Materials: All patients received external beam radiotherapy (elective target dose, 45 Gy in 25-30 fractions; tumor target dose, 50-60 Gy in 25-30 fractions). PDR-BT was applied with a tandem-ring applicator. Additional ring-guided titanium needles were used in 4 patients and a multichannel vaginal cylinder in 2 patients. Dose planning was done using 1.5 Tesla T{sub 1}-weighted and T{sub 2}-weighted paratransversal magnetic resonance imaging scans. T{sub 1}-weighted visible oil-containing tubes were used for applicator reconstruction. The prescribed standard dose for PDR-BT was 10 Gy (1 Gy/pulse, 1 pulse/h) for two to three fractions to reach a physical dose of 80 Gy to Point A. The total dose (external beam radiotherapy plus brachytherapy) was normalized to an equivalent dose in 2-Gy fractions using {alpha}/{beta} = 10 Gy for tumor, {alpha}/{beta} = 3 Gy for normal tissue, and a repair half-time of 1.5 h. The goal of optimization was dose received by 90% of the target volume (D{sub 90}) of {>=}85 Gy{sub {alpha}}{sub /{beta}}{sub 10} in the high-risk clinical target volume (cervix and remaining tumor at brachytherapy), but keeping the minimal dose to 2 cm{sup 3} of the bladder and rectum/sigmoid at <90 and <75 Gy{sub {alpha}}{sub /{beta}}{sub 3}, respectively. Results: Using three-dimensional optimization, all dose-volume histogram constraints were met in 16 of 21 patients compared with 3 of 21 patients with two-dimensional library plans (p < 0.001). Optimization increased the minimal target dose (D{sub 100}) of the high-risk clinical target volume (p < 0.007) and decreased the minimal dose to 2 cm{sup 3} for the sigmoid significantly (p = 0.03). For the high-risk clinical target volume, D

  19. Chemotherapy for Thyroid Cancer

    MedlinePlus

    ... cancer Next Topic Targeted therapy for thyroid cancer Chemotherapy for thyroid cancer Chemotherapy (chemo) uses anti-cancer drugs that are injected ... vein or muscle, or are taken by mouth. Chemotherapy is systemic therapy, which means that the drug ...

  20. Types of chemotherapy

    MedlinePlus

    Chemotherapy is the use of medicine to treat cancer. Chemotherapy kills cancer cells. It may be used to ... people are treated with a single type of chemotherapy. But often, people get more than one type ...

  1. Triple Negative Breast Cancer: Role of Specific Chemotherapy Agents

    PubMed Central

    Isakoff, Steven J.

    2010-01-01

    Cytotoxic chemotherapy remains the mainstay of treatment for triple negative breast cancer (TNBC) despite the promise of new targeted and biologic agents. Many studies have shown significant benefit of chemotherapy in the neoadjuvant, adjuvant and metastatic treatment of TNBC. Neoadjuvant chemotherapy studies have consistently reported higher response rates in TNBC than non-TNBC, and pathologic complete response has been shown to predict improved long term outcomes for TNBC. Although the specific adjuvant regimens that may be most effective for TNBC are still being determined, third generation chemotherapy regimens utilizing dose dense or metronomic polychemotherapy are among the most effective tools presently available. The role of specific chemotherapy agents in the treatment of TNBC remains incompletely defined and warrants careful review to ensure the most effective therapy is delivered while minimizing unnecessary toxicity. Platinum agents have seen renewed interest in TNBC based on a growing body of preclinical and clinical data suggesting encouraging activity. Taxanes and anthracyclines are active in TNBC and remain important agents, but have not shown specific benefit over non-TNBC. Capecitabine has limited reported data in TNBC, but some reports suggest differential activity in TNBC compared to hormone receptor positive breast cancer. TNBC is itself a heterogeneous group in which subgroups such as BRCA1 mutation carriers may have particular sensitivity to platinum agents and relatively less sensitivity to taxanes. Therefore, the identification of additional molecular biomarkers to predict response to specific chemotherapy is required to further improve treatment strategies with the current menu of chemotherapy options and future combinations with targeted therapies. PMID:20164691

  2. A Role for Orexin in Cytotoxic Chemotherapy-Induced Fatigue

    PubMed Central

    Weymann, K. B.; Wood, L. J.; Zhu, X.; Marks, D. L.

    2014-01-01

    Fatigue is the most common symptom related to cytotoxic chemotherapeutic treatment of cancer. Peripheral inflammation associated with cytotoxic chemotherapy is likely a causal factor of fatigue. The neural mechanisms by which cytotoxic chemotherapy associated inflammation induces fatigue behavior are not known. This lack of knowledge hinders development of interventions to reduce or prevent this disabling symptom. Infection induced fatigue/lethargy in rodents is mediated by suppression of hypothalamic orexin activity. Orexin is critical for maintaining wakefulness and motivated behavior. Though there are differences between infection and cytotoxic chemotherapy in some symptoms, both induce peripheral inflammation and fatigue. Based on these similarities we hypothesized that cytotoxic chemotherapy induces fatigue by disrupting orexin neuron activity. We found that a single dose of a cytotoxic chemotherapy cocktail (cyclophosphamide, adriamycin, 5-fluorouracil—CAF) induced fatigue/lethargy in mice and rats as evidenced by a significant decline in voluntary locomotor activity measured by telemetry. CAF induced inflammatory gene expression—IL-1R1 (p<0.001), IL-6 (p<0.01), TNFα (p<0.01), and MCP-1 (p<0.05) —in the rodent hypothalamus 6 to 24 hours after treatment during maximum fatigue/lethargy. CAF decreased orexin neuron activity as reflected by decreased nuclear cFos localization in orexin neurons 24 hours after treatment (p<0.05) and by decreased orexin-A in cerebrospinal fluid 16 hours after treatment (p<0.001). Most importantly, we found that central administration of1 μg orexin-A restored activity in CAF-treated rats (p<0.05). These results demonstrate that cytotoxic chemotherapy induces hypothalamic inflammation and that suppression of hypothalamic orexin neuron activity has a causal role in cytotoxic chemotherapy-induced fatigue in rodents. PMID:24216337

  3. Moderate-dose cyclophosphamide for severe aplastic anemia has significant toxicity and does not prevent relapse and clonal evolution.

    PubMed

    Scheinberg, Phillip; Townsley, Danielle; Dumitriu, Bogdan; Scheinberg, Priscila; Weinstein, Barbara; Daphtary, Maithili; Rios, Olga; Wu, Colin O; Young, Neal S

    2014-10-30

    First-line therapy of severe aplastic anemia (SAA) with high-dose cyclophosphamide causes toxicity and increased short-term mortality. We investigated cyclophosphamide at a lower, more moderate dose in combination with aggressive supportive care to determine whether severe infections might be avoided and hematologic outcomes defined for this regimen. From 2010 to 2012, 22 patients received cyclophosphamide at 120 mg/kg plus cyclosporine and antibacterial, antiviral, and antifungal prophylaxis. Toxicity was considerable, mainly due to prolonged absolute neutropenia, which occurred regardless of pretherapy blood counts, and persisted an average of 2 months. Granulocyte transfusions for uncontrolled infection were required in 5 patients, confirmed fungal infections were documented in 6, and 9 patients died. Nine patients (41%) responded at 6 months. After a median follow-up of 2.2 years, relapse occurred in 2 patients, and cytogenetic abnormalities (including monosomy 7) were observed in 4 patients. Although cyclophosphamide has activity in SAA, its toxicity is not justified when far less dangerous alternatives are available. This trial was registered at www.clinicaltrials.gov as #NCT01193283. PMID:25185712

  4. Chemotherapy for desmoid tumours in association with familial adenomatous polyposis: a report of three cases

    PubMed Central

    Hamilton, Lisa; Blackstein, Martin; Berk, Terri; McLeod, Robin S.; Gallinger, Steven; Madlensky, Lisa; Cohen, Zane

    1996-01-01

    Objective To determine the efficacy of chemotherapy for inoperable desmoid tumours associated with familial adenomatous polyposis. Design A review of three cases of unresectable desmoid tumours and of the literature on the subject. Setting The Steven Atanas Stavro Polyposis Registry at Mount Sinai Hospital in Toronto. Patients Three patients with symptomatic, unresectable desmoid tumours associated with familial adenomatous polyposis and unresponsive to conventional hormone therapy. Intervention A chemotherapy regimen of seven cycles of doxorubicin (dose ranging from 60 to 90 mg/m2) and dacarbazine (1000 mg/m2), followed by carboplatin (400 mg/m2) and dacarbazine. Outcome Measures Clinical improvement and tumour regression demonstrated by computed tomography. Results In each of the three cases significant tumour regression was seen clinically and radiologically. Conclusions Cytotoxic chemotherapy is an effective treatment for desmoid tumours associated with familial adenomatous polyposis. The chemotherapy should be started early in cases of symptomatic desmoid tumour unresponsive to conventional medical therapy. PMID:8640627

  5. Decrease of Let-7f in Low-Dose Metronomic Paclitaxel Chemotherapy Contributed to Upregulation of Thrombospondin-1 in Breast Cancer

    PubMed Central

    Tao, Wei-Yang; Liang, Xiao-Shuan; Liu, Yang; Wang, Chun-Yang; Pang, Da

    2015-01-01

    Low-dose metronomic (LDM) paclitaxel therapy displayed a stronger anti-angiogenic activity on breast tumors with fewer side effects. Upregulation of anti-angiogenic factor Thrombospondin-1 (TSP-1) accords for therapeutic potency of LDM paclitaxel, but its molecular mechanism has not been elucidated yet. microRNAs (miRNAs) have emerged as new important regulators of tumor growth and metastasis. Here, we hypothesize that miRNAs are involved in TSP-1 overexpression in paclitaxel LDM therapy of breast tumors. The miRNA profile of tumor tissues from control, LDM and MTD groups in 4T1 mouse breast cancer model was detected by microarray, and then verified by quantitative real-time PCR (qRT-PCR). Luciferase assay and western blot were employed to explore the mechanisms of miRNAs involved in this process. We found that let-7f, let-7a, miR-19b and miR-340-5p were reduced by >2 fold, and miR-543* and miR-684 were upregulated by at least 50% in paclitaxel LDM therapy. qRT-PCR verification revealed that let-7f level was reduced most significantly in LDM therapy. Computational prediction using TargetScan and miRanda suggested THBS1 which encodes TSP-1 as a potential target for let-7f. Luciferase activity assay further confirmed that let-7f may bind to 3'UTR of THBS1 gene and inhibit its activity. Moreover, forced expression of let-7f led to a decrease of TSP-1 at both mRNA and protein levels in MCF-7 cells. Contrastly, let-7f inhibition induced an increased expression of THBS1 mRNA and TSP-1 protein, but did not affect the proliferation and apoptosis of MCF-7 cells. Paclitaxel LDM therapy led to a decrease of let-7f and the elevation of TSP-1 protein expression in MCF-7 cells, while overexpression of let-7f may abolish LDM-induced the upregulation of TSP-1 in MCF-7 cells. In summary, let-7f inhibition contributed to the upregulation of TSP-1 in paclitaxel LDM therapy, independently of proliferation, cell cycle arrest and apoptosis of breast cancer. This study indicates let-7f

  6. Assessment of adherence to the guidelines for the management of nausea and vomiting induced by chemotherapy

    PubMed Central

    França, Monique Sedlmaier; Usón, Pedro Luiz Serrano; Antunes, Yuri Philippe Pimentel Vieira; Prado, Bernard Lobato; Donnarumma, Carlos del Cistia; Mutão, Taciana Sousa; Rodrigues, Heloisa Veasey; del Giglio, Auro

    2015-01-01

    ABSTRACT Objective: To assess adherence of the prescribing physicians in a private cancer care center to the American Society of Clinical Oncology guideline for antiemetic prophylaxis, in the first cycle of antineoplastic chemotherapy. Methods: A total of 139 chemotherapy regimens, of 105 patients, were evaluated retrospectively from 2011 to 2013. Results: We observed 78% of non-adherence to the guideline rate. The main disagreements with the directive were the prescription of higher doses of dexamethasone and excessive use of 5-HT3 antagonist for low risk emetogenic chemotherapy regimens. On univariate analysis, hematological malignancies (p=0.005), the use of two or more chemotherapy (p=0.05) and high emetogenic risk regimes (p=0.012) were factors statistically associated with greater adherence to guidelines. Treatment based on paclitaxel was the only significant risk factor for non-adherence (p=0.02). By multivariate analysis, the chemotherapy of high emetogenic risk most correlated with adherence to guideline (p=0.05). Conclusion: We concluded that the adherence to guidelines is greater if the chemotherapy regime has high emetogenic risk. Educational efforts should focus more intensely on the management of chemotherapy regimens with low and moderate emetogenic potential. Perhaps the development of a computer generated reminder may improve the adherence to guidelines. PMID:26154543

  7. The potential for Bayesian compressive sensing to significantly reduce electron dose in high-resolution STEM images.

    PubMed

    Stevens, Andrew; Yang, Hao; Carin, Lawrence; Arslan, Ilke; Browning, Nigel D

    2014-02-01

    The use of high-resolution imaging methods in scanning transmission electron microscopy (STEM) is limited in many cases by the sensitivity of the sample to the beam and the onset of electron beam damage (for example, in the study of organic systems, in tomography and during in situ experiments). To demonstrate that alternative strategies for image acquisition can help alleviate this beam damage issue, here we apply compressive sensing via Bayesian dictionary learning to high-resolution STEM images. These computational algorithms have been applied to a set of images with a reduced number of sampled pixels in the image. For a reduction in the number of pixels down to 5% of the original image, the algorithms can recover the original image from the reduced data set. We show that this approach is valid for both atomic-resolution images and nanometer-resolution studies, such as those that might be used in tomography datasets, by applying the method to images of strontium titanate and zeolites. As STEM images are acquired pixel by pixel while the beam is scanned over the surface of the sample, these postacquisition manipulations of the images can, in principle, be directly implemented as a low-dose acquisition method with no change in the electron optics or the alignment of the microscope itself. PMID:24151325

  8. Impact of obesity in favorable-risk AML patients receiving intensive chemotherapy.

    PubMed

    Tavitian, Suzanne; Denis, Amélia; Vergez, François; Berard, Emilie; Sarry, Audrey; Huynh, Anne; Delabesse, Eric; Luquet, Isabelle; Huguet, Françoise; Récher, Christian; Bertoli, Sarah

    2016-02-01

    We assessed the influence of obesity on the characteristics and prognosis of acute myeloid leukemia (AML). Indeed, safety of intensive chemotherapy and outcome of obese AML patients in a real-life setting are poorly described, and chemotherapy dosing remains challenging. We included 619 consecutive genetically-defined cases of AML treated with intensive chemotherapy between 2004 and 2012. In this cohort, 93 patients (15%) were classified in the obese category according to WHO classification; 59% of them received capped doses of chemotherapy because of a body surface area above 2 m(2) . Obese patients were older and presented more often with cardiovascular comorbidities. Although obese patients had more frequently de novo AML, main characteristics of AML including white blood cell count, karyotype and mutations were well-balanced between obese and non-obese patients. After induction chemotherapy, early death and complete remission rates were similar. Overall (OS), event-free (EFS) and disease-free (DFS) survival were not significantly different compared to non-obese patients. However, in the European LeukemiaNet (ELN) favorable subgroup, obese patients had lower median OS, EFS and DFS than non-obese patients (18.4, 16.8 and 17.2 vs. 43.6, 31.8 and 29.7 months, respectively) and obesity showed a significant impact on OS (OR 2.54; P = 0.02) in multivariate models. Although we did not find any significant impact of obesity on outcome in the whole series, this study suggests that special efforts for chemotherapy dose optimization are needed in the ELN favorable subgroup since dose capping may be deleterious. PMID:26509505

  9. Epigenetic priming with decitabine followed by low-dose idarubicin/cytarabine has an increased anti-leukemic effect compared to traditional chemotherapy in high-risk myeloid neoplasms.

    PubMed

    Ye, Xing-Nong; Zhou, Xin-Ping; Wei, Ju-Ying; Xu, Gai-Xiang; Li, Ying; Mao, Li-Ping; Huang, Jian; Ren, Yan-Ling; Mei, Chen; Wang, Jing-Han; Lou, Yin-Jun; Ma, Li-Ya; Yu, Wen-Juan; Ye, Li; Xie, Li-Li; Luo, Yin-Wan; Hu, Chao; Niu, Lin-Mei; Dou, Min-Hua; Jin, Jie; Tong, Hong-Yan

    2016-06-01

    Decitabine (DAC) is commonly used for the treatment of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Previous studies have indicated DAC sequentially combined with idarubicin was an effective treatment for myeloid neoplasms. Therefore, a clinical study was conducted of the sequential combination of DAC followed by low-dose idarubicin/cytarabine in high-risk myeloid neoplasms. A total of 30 patients with a diagnosis of high-risk MDS, AML evolving from MDS or relapsed/refractory AML were enrolled in the study. DAC was administered 20 mg/m(2) daily for 3 consecutive days. Idarubicin (3 mg/m(2)/day) was administered 24 h after the last administration of DAC for 5-7 consecutive days, combined with cytarabine (30 mg/m(2)/day) for 7-14 days. The overall complete remission rate was 66.67%. The results demonstrate that epigenetic priming with decitabine followed by low-dose idarubicin/ytarabine has an increased anti-leukemia effect compared to traditional chemotherapy in high-risk myeloid neoplasms. PMID:26372888

  10. Repeated dose (28-day) administration of silver nanoparticles of varied size and coating does not significantly alter the indigenous murine gut microbiome.

    PubMed

    Wilding, Laura A; Bassis, Christine M; Walacavage, Kim; Hashway, Sara; Leroueil, Pascale R; Morishita, Masako; Maynard, Andrew D; Philbert, Martin A; Bergin, Ingrid L

    2016-01-01

    Silver nanoparticles (AgNPs) have been used as antimicrobials in a number of applications, including topical wound dressings and coatings for consumer products and biomedical devices. Ingestion is a relevant route of exposure for AgNPs, whether occurring unintentionally via Ag dissolution from consumer products, or intentionally from dietary supplements. AgNP have also been proposed as substitutes for antibiotics in animal feeds. While oral antibiotics are known to have significant effects on gut bacteria, the antimicrobial effects of ingested AgNPs on the indigenous microbiome or on gut pathogens are unknown. In addition, AgNP size and coating have been postulated as significantly influential towards their biochemical properties and the influence of these properties on antimicrobial efficacy is unknown. We evaluated murine gut microbial communities using culture-independent sequencing of 16S rRNA gene fragments following 28 days of repeated oral dosing of well-characterized AgNPs of two different sizes (20 and 110 nm) and coatings (PVP and Citrate). Irrespective of size or coating, oral administration of AgNPs at 10 mg/kg body weight/day did not alter the membership, structure or diversity of the murine gut microbiome. Thus, in contrast to effects of broad-spectrum antibiotics, repeat dosing of AgNP, at doses equivalent to 2000 times the oral reference dose and 100-400 times the effective in vitro anti-microbial concentration, does not affect the indigenous murine gut microbiome. PMID:26525505

  11. Semimechanistic cell-cycle type-based pharmacokinetic/pharmacodynamic model of chemotherapy-induced neutropenic effects of diflomotecan under different dosing schedules.

    PubMed

    Mangas-Sanjuan, Víctor; Buil-Bruna, Núria; Garrido, María J; Soto, Elena; Trocóniz, Iñaki F

    2015-07-01

    The current work integrates cell-cycle dynamics occurring in the bone marrow compartment as a key element in the structure of a semimechanistic pharmacokinetic/pharmacodynamic model for neutropenic effects, aiming to describe, with the same set of system- and drug-related parameters, longitudinal data of neutropenia gathered after the administration of the anticancer drug diflomotecan (9,10-difluoro-homocamptothecin) under different dosing schedules to patients (n = 111) with advanced solid tumors. To achieve such an objective, the general framework of the neutropenia models was expanded, including one additional physiologic process resembling cell cycle dynamics. The main assumptions of the proposed model are as follows: within the stem cell compartment, proliferative and quiescent cells coexist, and only cells in the proliferative condition are sensitive to drug effects and capable of following the maturation chain. Cell cycle dynamics were characterized by two new parameters, FProl (the fraction of proliferative [Prol] cells that enters into the maturation chain) and kcycle (first-order rate constant governing cell cycle dynamics within the stem cell compartment). Both model parameters were identifiable as indicated by the results from a bootstrap analysis, and their estimates were supported by date from the literature. The estimates of FProl and kcycle were 0.58 and 1.94 day(-1), respectively. The new model could properly describe the neutropenic effects of diflomotecan after very different dosing scenarios, and can be used to explore the potential impact of dosing schedule dependencies on neutropenia prediction. PMID:25948593

  12. The Effect of Significant Tumor Reduction on the Dose Distribution in Intensity Modulated Radiation Therapy for Head-And-Neck Cancer: A Case Study

    SciTech Connect

    Mechalakos, James Lee, Nancy; Hunt, Margie; Ling, C. Clifton; Amols, Howard I.

    2009-10-01

    We present a unique case in which a patient with significant tissue loss was monitored for dosimetric changes using weekly cone beam computed tomography (CBCT) scans. A previously treated nasopharynx patient presented with a large, exophytic, recurrent left neck mass. The patient underwent re-irradiation to 70 Gy using intensity modulated radiation therapy (IMRT) with shielding blocks over the spinal cord and brain stem. Weekly CBCT scans were acquired during treatment. Target contours and treatment fields were then transferred from the original treatment planning computed tomography (CT) to the CBCT scans and dose calculations were performed on all CBCT scans and compared to the planning doses. In addition, a 'research' treatment plan was created that assumed the patient had not been previously treated, and the above analysis was repeated. Finally, to remove the effects of setup error, the outer contours of 2 CBCT scans with significant tumor reductions were transferred to the planning scan and dose in the planning scan was recalculated. Planning treatment volume (PTV) decreased 45% during treatment. Spinal cord D05 differed from the planned value by 3.5 {+-} 9.8% (average + standard deviation). Mean dose to the oral cavity and D05 of the mandible differed from the planned value by 0.9 {+-} 2.1% and 0.6 {+-} 1.5%, respectively. Results for the research plan were comparable. Target coverage did not change appreciably (-0.2 {+-} 2.5%). When the planning scan was recalculated with the reduced outer contour from the CBCT, spinal cord D05 decreased slightly due to the reduction in scattered dose. Weekly imaging provided us the unique opportunity to use different methods to examine the dosimetric effects of an unusually large loss of tissue. We did not see that tissue loss alone resulted in a significant effect on the dose delivered to the spinal cord for this case, as most fluctuation was due to setup error. In the IGRT era, delivered dose distributions can be more

  13. A phase II, randomized study of aprepitant in the prevention of chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapies in colorectal cancer patients

    PubMed Central

    ARIDOME, KUNIAKI; MORI, SHIN-ICHIROU; BABA, KENJI; YANAGI, MASAYUKI; HAMANOUE, MASAHIRO; MIYAZONO, FUTOSHI; TOKUDA, KOUKI; IMAMURA, HIROSHI; OGURA, YOSHITO; KANEKO, KOUICHI; KIJIMA, FUMIO; MAEMURA, KOUSEI; ISHIGAMI, SUMIYA; NATSUGOE, SHOJI

    2016-01-01

    The present study aimed to study the efficacy of aprepitant in the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy (MEC) for colorectal cancer (CRC), and comprised a multicenter, phase II, open-label, randomized, parallel comparative study conducted as part of the Kagoshima aprepitant study for colon cancer in Japan. Patients with advanced or recurrent CRC were treated with standard MEC regimens (FOLFOX, XELOX or FOLFIRI) and received either standard chemotherapy [5-hydroxytryptamine-3 receptor antagonist (5-HT3RA) + dexamethasone] or aprepitant regimen chemotherapy (5-HT3 RA + reduced-dose dexamethasone + aprepitant). The primary endpoint of the present study was the proportion of patients who achieved a complete response (CR) during the overall, acute, and delayed phases of the first planned chemotherapy cycle. Secondary endpoints were complete protection, the proportions of patients without emetic episodes or nausea, patients with no more than moderate nausea during the overall, acute and delayed phases, and the time to treatment failure. The CR rates in the overall, acute and delayed phases were similar in the aprepitant and the standard-regimen groups. Additionally, there were no significant differences in secondary endpoints between the two groups. In summary, aprepitant in combination with 5-HT3 RA and reduced-dose corticosteroids was well tolerated and effective in preventing CINV associated with moderately emetogenic antitumor agents in Japanese patients with CRC. PMID:26998290

  14. [Clinical Investigation of the Effects of Filgrastim BS1 on Neutropenia Following Oral Cancer Chemotherapy (TPF Therapy)].

    PubMed

    Uchiyama, Kimio; Yamada, Manabu; Tamate, Shusuke; Iwasaki, Konomi; Mitomo, Keisuke; Nakayama, Seiichi

    2015-09-01

    The time for the neutrophil count to recover after subcutaneous injection of filgrastim BS1 or lenograstim was studied in patients suffering from neutropenia following preoperative combined chemotherapy using docetaxel, nedaplatin, or cisplatin (in divided doses for 5 days)and 5-fluorouracil for oral cancer. 1. There was no significant difference in the minimum leukocyte and neutrophil counts after chemotherapy. 2. There was no significant difference in the maximum leukocyte and neutrophil counts after chemotherapy. 3. Time for leukocytes to recover from their minimum count(>4,000/mm3)or for neutrophils to recover from their minimum count(>2,000/mm3)and the number of days on which treatment was administered tended to be shorter in the filgrastim BS1 group. Thus, it was concluded that filgrastim BS1 is just as effective as other prior G-CSF agents in treating patients suffering from neutropenia following chemotherapy(TPF therapy). PMID:26469162

  15. [Efficacy of Postoperative Chemotherapy in Stage Ⅳ Colorectal Cancer with Perforation].

    PubMed

    Onozawa, Hisashi; Kumamoto, Kensuke; Matsuzawa, Takeaki; Ishiguro, Toru; Sobajima, Jun; Fukuchi, Minoru; Kumagai, Youichi; Ishibashi, Keiichiro; Mochiki, Erito; Ishida, Hideyuki

    2015-11-01

    The clinical outcome and efficacy of postoperative chemotherapy in patients with Stage Ⅳ colorectal cancer with perforation were investigated. We compared the clinical outcomes between 11 patients with Stage Ⅳ colorectal cancer (perforation group), who underwent emergency surgery for colonic perforation between September 2005 and March 2012, and 22 matched patients (matching group) who underwent elective colorectal surgery during the same period. The colostomy rate in the perforation group was significantly higher than that of the matching group: patients with perforation received stoma construction surgery more frequently (p<0.01). Seven patients (64%) in the perforation group received postoperative chemotherapy, while 20 patients (91%) in the matching group received chemotherapy (p=0.15). Oxaliplatin-based chemotherapy was administered to all patients in both groups. There was no difference in the median relative dose intensity of oxaliplatin between these groups (p=0.37). No significant difference was observed between the cumulative 3-year overall survival rate in the perforation group and that of the matching group (35% and 54%, respectively; p=0.35). Moreover, the 3-year overall survival rates of patients who received oxaliplatin-based chemotherapy were 51%in the perforation group and 57% in the matching group (p=0.74). Our results suggest that postoperative oxaliplatin-based chemotherapy may improve the prognosis of patients with Stage Ⅳ colorectal cancer with perforation. PMID:26805324

  16. Comparison of Total Body Irradiation Before and After Chemotherapy in Pretreatment for Hematopoietic Stem Cell Transplantation

    PubMed Central

    Li, De-Zhi; Kong, Pei-Yan; Wang, Xin-Xin; Li, Guang-Hui; Zhou, Yi-Bing; Chen, Zheng-Tang

    2012-01-01

    Abstract Objective To explore the best time to carry out total body irradiation (TBI) in hematopoietic stem cell transplantation (HSCT) pretreatment. Methods Retrospective analysis was applied in 88 cases of HSCT using TBI as pretreatment from March 2001 to June 2009 in our hospital. Using 8 MV X-ray, all the patients were irradiated by linear accelerator in 2 consecutive days, with a total dose of 7–11 Gy and an instantaneous dose rate ranging between 4.0 and 5.0 cGy/min. Of the 88 cases, 40 cases were given traditional high-dose chemotherapy before TBI (Group CT/TBI), and 48 cases were given TBI before chemotherapy (Group TBI/CT) instead. Results Eighty-seven cases of transplantation were successful, with no serious complications, including radiation pneumonia. Compared with Group CT/TBI, Group TBI/CT showed similar incidence of complications (p=0.08), similar recent chemotherapy toxicity (p=0.833), and significantly lower recent radiation toxicity (p=0.000). Conclusions TBI in the pretreatment of HSCT is safe and effective. Using TBI before the high-dose chemotherapy can maintain the same pretreatment effect, effectively reduce apparent immediate reaction/discomfort during TBI, reduce preparation workload of radiotherapy, and lower radiation side-effects. Further research is needed to expand its clinical application. PMID:22149642

  17. Romiplostim promotes platelet recovery in a mouse model of multicycle chemotherapy-induced thrombocytopenia.

    PubMed

    McElroy, Patricia L; Wei, Ping; Buck, Keri; Sinclair, Angus M; Eschenberg, Michael; Sasu, Barbra; Molineux, Graham

    2015-06-01

    Chemotherapy-induced thrombocytopenia can lead to chemotherapy treatment delays or dose reductions. The ability of romiplostim, a thrombopoietin (TPO) mimetic, to promote platelet recovery in a mouse model of multicycle chemotherapy/radiation therapy (CRT)-induced thrombocytopenia was examined. In humans, an inverse relationship between platelet counts and endogenous TPO (eTPO) concentration exists. In a CRT mouse model, eTPO was not elevated during the first 5 days after CRT treatment (the "eTPO gap"), then increased to a peak 10 days after each CRT treatment in an inverse relationship to platelet counts seen in humans. To bridge the eTPO gap, mice were treated with 10-1,000 μg/kg of romiplostim on day 0, 1, or 2 after CRT. In some mice, the romiplostim dose was approximately divided over 3 days. Platelet recovery occurred faster with romiplostim in most conditions tested. Romiplostim doses of ≥100 μg/kg given on day 0 significantly lessened the platelet nadir. Fractionating the dose over 3 days did not appear to confer a large advantage. These data may provide a rationale for clinical studies of romiplostim in chemotherapy-induced thrombocytopenia. PMID:25754671

  18. Effect of Previous Chemotherapy on the Quality of Cryopreserved Human Ovarian Tissue In Vitro

    PubMed Central

    Asadi Azarbaijani, Babak; Sheikhi, Mona; Oskam, Irma C.; Nurmio, Mirja; Laine, Tiina; Tinkanen, Helena; Mäkinen, Sirpa; Tanbo, Tom G.; Hovatta, Outi; Jahnukainen, Kirsi

    2015-01-01

    Background Cryopreservation of ovarian tissue has been widely accepted as an option for fertility preservation among cancer patients. Some patients are exposed to chemotherapy prior to ovarian tissue cryopreservation. Consequently, assessment of the developmental capacity of human ovarian tissue after chemotherapy is of primary importance. Materials In order to study the impact of previous chemotherapy on in vitro development and viability of ovarian follicles, quality control samples from 34 female cancer patients at median age of 15 years (range 1‒35), cryopreserved for fertility preservation before (n = 14) or after (n = 20) initiation of chemotherapy, were thawed and cultured for 7 days. The morphology and developmental stages of ovarian follicles were studied by light microscopy before and after culture. Possible associations between follicular densities, age and exposure to alkylating agents, expressed as cyclophosphamide equivalent dose (CED) were tested. Results Exposure to chemotherapy significantly impaired the survival and development of ovarian follicles in culture. After seven days, significantly higher densities of intermediary, primary and secondary follicles and lower densities of atretic follicles was detected in the samples collected before chemotherapy. Increasing dose of alkylating agents was identified by multivariate linear regression analysis as an independent predictor of a higher density of atretic follicles, whereas increasing age of the patient predicted a better outcome with less follicle atresia and a higher density of maturing follicles. Conclusion This study provides quantitative in vitro evidence of the impact of chemotherapy on developmental capacity of cryopreserved human ovarian tissue. The results indicate that fertility preservation should be carried out, if possible, before initiation of alkylating agents in order to guarantee better in vitro survival of ovarian follicles. In addition, ovarian samples from younger girls show

  19. Significance of higher drug concentration in erythrocytes of mice infected with Schistosoma japonicum and treated orally with mefloquine at single doses.

    PubMed

    Tao, Yi; Xue, Jian; Jiang, Bin; Zhang, Hao-Bing; Xiao, Shu-Hua

    2015-12-01

    The purpose of the present study is to understand the pharmacokinetic feature of mefloquine measured by erythrocytes and plasma in Schistosoma japonicum (S. j.)-infected mice and non-infected mice after oral administration of the drug at single doses. A high-performance liquid chromatography (HPLC) method was used to measure the plasma and erythrocyte concentrations of mefloquine at varying intervals posttreatment. Our results demonstrated that in non-infected mice treated orally with mefloquine at an ineffective dose of 50 mg/kg or effective dose of 200 mg/kg for 2-72 h, the erythrocyte-to-plasma ratios of mefloquine were 5.8-11.2 or 2-14.2. On the other hand, in S. j.-infected mice treated with the same single doses of the drug, the erythrocyte and plasma drug concentration ratios were 3.1-4.6 or 2.9-8.5, manifesting that either in infected mice or in non-infected mice that received oral mefloquine resulted in higher concentration of mefloquine in erythrocytes than that in plasma. Unexpectedly, under oral administration of mefloquine at a higher single dose of 200 mg/kg, the pharmacokinetic parameter C max values for plasma from S. j.-infected and non-infected mice were 1.6 ± 0.3 and 2.0 ± 0.4 μg/mL, respectively, which were below the determined in vitro LC50 (50 % lethal concentration) value of 4.93 μg/mL. Therefore, the plasma concentration of mefloquine may display a little effect against schistosomes during the treatment. Although the values of T 1/2 and AUC0-∞ for erythrocytes were significantly longer and higher in infected mice than those of corresponding non-infect mice that received the same single mefloqine dose of 50 mg/kg, the C max value was only 2.6 ± 0.4 μg/mL lower than the determined in vitro LC50, which may explain why this low single dose is ineffective against schistosomes in vivo. After administration of higher mefloquine dose of 200 mg/kg, the C max value for erythrocytes in infected mice was 30 % (7.4 ± 0

  20. The Prospective Oral Mucositis Audit: relationship of severe oral mucositis with clinical and medical resource use outcomes in patients receiving high-dose melphalan or BEAM-conditioning chemotherapy and autologous SCT.

    PubMed

    McCann, S; Schwenkglenks, M; Bacon, P; Einsele, H; D'Addio, A; Maertens, J; Niederwieser, D; Rabitsch, W; Roosaar, A; Ruutu, T; Schouten, H; Stone, R; Vorkurka, S; Quinn, B; Blijlevens, N

    2009-01-01

    The Prospective Oral Mucositis Audit was an observational study in 197 patients with multiple myeloma (MM) or non-Hodgkin's lymphoma (NHL) undergoing, respectively, high-dose melphalan or BEAM chemotherapy and autologous SCT at 25 European centres. We evaluated the relationship between severe oral mucositis (SOM; WHO Oral Toxicity Scale grade 3-4) and local and systemic clinical sequelae and medical resource use. SOM occurred in 44% of patients. The duration of SOM (mean 5.3 days) correlated with time to neutrophil engraftment. The following parameters increased gradiently with maximum grade of oral mucositis: duration of pain score >or=4, opioid use, dysphagia score >or=4, total parenteral nutrition (TPN) use, incidence and/or duration of fever and infection, and duration of antibiotic use. SOM increased the duration of TPN use by 2.7 days (P<0.001), opioids by 4.6 days (P<0.001), and antibiotics by 2.4 days (P=0.045). SOM prolonged hospital stay by 2.3 days (P=0.013) in MM patients, but not in NHL patients (who tended to have a longer hospital stay). In conclusion, this analysis of prospectively collected observational data provides important insight into the scope and impact of SOM in the European transplant setting. PMID:18776926

  1. The effect of postoperative radiotherapy on the feasibility of optimal dose adjuvant CMF chemotheraphy in stage II breast carcinoma

    SciTech Connect

    Sulkes, A.; Brufman, G.; Rizel, S.; Weshler, Z.; Biran, S.; Fuks, Z.

    1983-01-01

    The impact of a number of variables upon the effectiveness of adjuvant chemotherapy given to 87 patients with Stage II breast carcinoma was retrospectively analyzed. Adjuvant chemotherapy consisted of cyclophosphamide, methotrexate and 5-fluorouracil (CMF). Drugs were given in optimal doses (85% or more of the planned dose) to 17% of the patients; in intermediate doses (66 to 84% of the planned dose) to 50% of the patients; and in low doses (65% or less of the planned dose) to 33% of the patients. Myelosuppression was the main reason for giving intermediate or low doses. At a median follow-up of three years, 84% of all patients remain alive. Radiation therapy preceding chemotherapy was given to 70% of the patients, concomitant irradation and chemotherapy to 15%, and 13 patients (15%) received chemotheapy only. Of the 14 patients who received optimal doses of CMF, 12 (86%) also received radiation therapy. Disease-free survival at three years is similar for irradiated and nonirradiated patients, but the latter have a higher incidence of local recurrence (5% vs. 15%), although the difference is not statistically significant. Delay in the intiation of chemotherapy, mostly because of the administration of postoperative irradiation, adversely affected the probability and duration of disease-free survival, particulararly in premenopausal women in whom chemotherapy was started within more than 90 days of mastectomy. The administration of optimal doses of adjuvant chemotherapy should follow the primary treatment to the breast tumor as closely as possible. If radiation therapy is indicated as well, it should be delivered concomitantly with chemotherapy, given the feasibility of administering both modalities simultaneously, as demonstrated in this study.

  2. Changes in allelic imbalances in locally advanced breast cancers after chemotherapy

    PubMed Central

    Varna, M; Soliman, H; Feugeas, J-P; Turpin, E; Chapelin, D; Legrès, L; Plassa, L-F; de Roquancourt, A; Espié, M; Misset, J-L; Janin, A; de Thé, H; Bertheau, P

    2007-01-01

    In advanced breast cancers, TP53 mutation is highly predictive of complete response to high-dose epirubicin/cyclophosphamide chemotherapy. In these tumours with an altered control of genomic stability, accumulation of chemotherapy-induced genetic alterations may contribute to cell death and account for complete response. To explore the effects of chemotherapy on stability of the tumour genome, allelic profiles were obtained from microdissected tumour samples before and after chemotherapy in 29 unresponsive breast cancers (9 with TP53 mutation). Ninety-four per cent allelic profiles remained unchanged after treatment. Interestingly, 11 profiles (6%) showed important changes after treatment; allelic imbalances significantly increased (four cases) or decreased (seven cases) after chemotherapy in three distinct experiments, two of which using laser microdissected tumour cells. These genetic changes were not linked to the TP53 status, but one tumour showed complete disappearance of TP53-mutated cells in the residual tumour after treatment. Altogether, these observations carry important implications for the clonal evolution of breast cancers treated with DNA-damaging agents, as they point both to the importance of tumour heterogeneity and chemotherapy-driven selection of subclones. PMID:17876337

  3. Management of Chemotherapy Induced Nausea and Vomiting in Patients on Multiday Cisplatin Based Combination Chemotherapy

    PubMed Central

    Ranganath, Praveen; Einhorn, Lawrence; Albany, Costantine

    2015-01-01

    Introduction of cisplatin based chemotherapy has revolutionized the treatment of germ cell tumors. A common side effect of multiday cisplatin chemotherapy is severe nausea and vomiting. Considerable progress has been made in the control of these side effects since the introduction of cisplatin based chemotherapy in the 1970s. Germ cell tumor which is a model for a curable neoplasm has also turned into an excellent testing ground to develop effective strategies to prevent chemotherapy induced nausea and vomiting (CINV) in multiday cisplatin based regimens. The use of combination of a 5-hydroxytryptamine (HT)3 receptor antagonist, a neurokinin-1 (NK1) antagonist, and dexamethasone has greatly improved our ability to prevent and control acute and delayed CINV. Mechanism and pattern of CINV with multiday chemotherapy may differ from those in single day chemotherapy and therefore efficacy of antiemetic drugs as observed in single day chemotherapy may not be applicable. There are only few randomized clinical trials with special emphasis on multiday chemotherapy. Further studies are essential to determine the efficacy, optimal dose, and duration of the newer agents and combinations in multiday cisplatin based chemotherapy. PMID:26425563

  4. Canine Osteosarcoma Treated by Post-Amputation Sequential Accelerated Doxorubicin and Carboplatin Chemotherapy: 38 Cases.

    PubMed

    Frimberger, Angela E; Chan, Catherine M; Moore, Antony S

    2016-01-01

    Canine appendicular osteosarcoma is an important clinical problem in veterinary medicine. Current standard therapy includes amputation followed by chemotherapy, which improves outcomes; however the percentage of long-term survival is still relatively low at 15-20%. Established prognostic factors include serum alkaline phosphatase level, histologic grade, and lymphocyte and monocyte counts. We used a protocol with shorter inter-treatment intervals than standard, but which we expected to still be well-tolerated, based on drugs known to be active agents, with the aim of improving outcomes by increasing dose intensity. Thirty-eight dogs with confirmed appendicular osteosarcoma and no pulmonary metastases that underwent amputation followed by this chemotherapy protocol were retrospectively evaluated. The median survival time was 317 days and 1- and 2-yr survival percentages were 43.2% and 13.9%, respectively. Toxicity was comparable to that seen with other standard dose protocols, with 5.2% of dogs hospitalized for complications that resolved with supportive care and no chemotherapy-related mortality. Serum alkaline phosphatase level (normal or high) (p = 0.004) and whether or not chemotherapy was completed (p = 0.001) were found to significantly impact survival time on multivariate analysis. Outcomes were similar to those reported with most other published chemotherapy protocols for dogs with this disease. PMID:27008320

  5. Chemotherapy for malignant brain tumors of childhood

    PubMed Central

    Gottardo, Nicholas G.; Gajjar, Amar

    2009-01-01

    During the past 3 decades, chemotherapeutic agents have been extensively evaluated for the treatment of pediatric brain tumors in a myriad of schedules, doses, and combinations. Remarkable advances in outcome have been achieved for certain groups of children, notably those with medulloblastoma, and chemotherapy has played a key role. However, improvements in survival are obtained at a high cost to quality of life. In addition, the success achieved for medulloblastoma is offset by a lack of progress for high-grade glioma. Despite decades of intensive investigation, no single chemotherapeutic regimen stands out as particularly beneficial for children with high-grade glioma, with the vast majority of these patients succumbing to their disease. A plateau in efficacy has been reached. Further treatment intensification using conventional nonspecific chemotherapy is more likely to result in additional toxicity without major advances in survival. Genomewide analysis using microarray technology has contributed significantly to our understanding of tumor biology. This knowledge has shifted the focus onto novel agents that target molecular changes crucial for tumor proliferation or survival. These selective agents are likely to be less toxic to normal cells and it is anticipated they will be more effective than the nonspecific chemotherapeutic agents currently used. PMID:18952581

  6. Adjuvant chemotherapy and acute toxicity in hypofractionated radiotherapy for early breast cancer

    PubMed Central

    Kouloulias, Vassilis; Zygogianni, Anna; Kypraiou, Efrosini; Georgakopoulos, John; Thrapsanioti, Zoi; Beli, Ivelina; Mosa, Eftychia; Psyrri, Amanta; Antypas, Christos; Armbilia, Christina; Tolia, Maria; Platoni, Kalliopi; Papadimitriou, Christos; Arkadopoulos, Nikolaos; Gennatas, Costas; Zografos, George; Kyrgias, George; Dilvoi, Maria; Patatoucas, George; Kelekis, Nikolaos; Kouvaris, John

    2014-01-01

    AIM: To evaluate the effect of chemotherapy to the acute toxicity of a hypofractionated radiotherapy (HFRT) schedule for breast cancer. METHODS: We retrospectively analyzed 116 breast cancer patients with T1, 2N0Mx. The patients received 3-D conformal radiotherapy with a total physical dose of 50.54 Gy or 53.2 Gy in 19 or 20 fractions according to stage, over 23-24 d. The last three to four fractions were delivered as a sequential tumor boost. All patients were monitored for acute skin toxicity according to the European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group criteria. The maximum monitored value was taken as the final grading score. Multivariate analysis was performed for the contribution of age, chemotherapy and 19 vs 20 fractions to the radiation acute skin toxicity. RESULTS: The acute radiation induced skin toxicity was as following: grade I 27.6%, grade II 7.8% and grade III 2.6%. No significant correlation was noted between toxicity grading and chemotherapy (P = 0.154, χ2 test). The mean values of acute toxicity score in terms of chemotherapy or not, were 0.64 and 0.46 respectively (P = 0.109, Mann Whitney test). No significant correlation was also noted between acute skin toxicity and radiotherapy fractions (P = 0.47, χ2 test). According to univariate analysis, only chemotherapy contributed significantly to the development of acute skin toxicity but with a critical value of P = 0.05. However, in multivariate analysis, chemotherapy lost its statistical significance. None of the patients during the 2-years of follow-up presented any locoregional relapse. CONCLUSION: There is no clear evidence that chemotherapy has an impact to acute skin toxicity after an HFRT schedule. A randomized trial is needed for definite conclusions. PMID:25405195

  7. Prognostic Significance of Carbohydrate Antigen 19-9 in Unresectable Locally Advanced Pancreatic Cancer Treated With Dose-Escalated Intensity Modulated Radiation Therapy and Concurrent Full-Dose Gemcitabine: Analysis of a Prospective Phase 1/2 Dose Escalation Study

    SciTech Connect

    Vainshtein, Jeffrey M.; Schipper, Matthew; Zalupski, Mark M.; Lawrence, Theodore S.; Abrams, Ross; Francis, Isaac R.; Khan, Gazala; Leslie, William; Ben-Josef, Edgar

    2013-05-01

    Purpose: Although established in the postresection setting, the prognostic value of carbohydrate antigen 19-9 (CA19-9) in unresectable locally advanced pancreatic cancer (LAPC) is less clear. We examined the prognostic utility of CA19-9 in patients with unresectable LAPC treated on a prospective trial of intensity modulated radiation therapy (IMRT) dose escalation with concurrent gemcitabine. Methods and Materials: Forty-six patients with unresectable LAPC were treated at the University of Michigan on a phase 1/2 trial of IMRT dose escalation with concurrent gemcitabine. CA19-9 was obtained at baseline and during routine follow-up. Cox models were used to assess the effect of baseline factors on freedom from local progression (FFLP), distant progression (FFDP), progression-free survival (PFS), and overall survival (OS). Stepwise forward regression was used to build multivariate predictive models for each endpoint. Results: Thirty-eight patients were eligible for the present analysis. On univariate analysis, baseline CA19-9 and age predicted OS, CA19-9 at baseline and 3 months predicted PFS, gross tumor volume (GTV) and black race predicted FFLP, and CA19-9 at 3 months predicted FFDP. On stepwise multivariate regression modeling, baseline CA19-9, age, and female sex predicted OS; baseline CA19-9 and female sex predicted both PFS and FFDP; and GTV predicted FFLP. Patients with baseline CA19-9 ≤90 U/mL had improved OS (median 23.0 vs 11.1 months, HR 2.88, P<.01) and PFS (14.4 vs 7.0 months, HR 3.61, P=.001). CA19-9 progression over 90 U/mL was prognostic for both OS (HR 3.65, P=.001) and PFS (HR 3.04, P=.001), and it was a stronger predictor of death than either local progression (HR 1.46, P=.42) or distant progression (HR 3.31, P=.004). Conclusions: In patients with unresectable LAPC undergoing definitive chemoradiation therapy, baseline CA19-9 was independently prognostic even after established prognostic factors were controlled for, whereas CA19-9 progression

  8. Toxicity of (neo)adjuvant chemotherapy for BRCA1- and BRCA2-associated breast cancer.

    PubMed

    Drooger, Jan C; Heemskerk-Gerritsen, Bernadette A M; Smallenbroek, Nyrée; Epskamp, Cynthia; Seynaeve, Caroline M; Jager, Agnes

    2016-04-01

    Treatment with (neo)adjuvant chemotherapy for breast cancer, as currently given, causes cell damage by induction of double-strand DNA breaks. Because BRCA1 and BRCA2 proteins play a role in the repair of DNA damage, the efficacy of (neo)adjuvant chemotherapy may be increased in BRCA1/2-associated breast cancer patients. As a downside, acute chemotherapy-related toxicity may also be increased. We selected all female patients who were treated at the Erasmus MC Cancer Institute, with (neo)adjuvant chemotherapy for primary or locoregional recurrence of breast cancer (PBC/LR) between January 1, 2004 and December 31, 2014. The primary outcome was the relative total dose intensity (RTDI), calculated for anthracyclines and taxanes separately. Secondary outcomes were the occurrence of febrile neutropenia, delay in chemotherapy administration, and switch to another chemotherapy regimen due to toxicity. In total, 701 patients treated for PBC/LR were eligible for data analyses, among which 85 BRCA1/2 mutation carriers (n = 67 BRCA1 and n = 18 BRCA2). The mean RTDI for anthracyclines was not significantly different between both groups (98.7 % in the BRCA1/2, 96.6 % in the sporadic group, p = 0.27). Also the mean RTDI for taxanes was not significantly different between the groups (93.6 % in the BRCA1/2-associated, 90.0 % in the sporadic group, p = 0.12). Linear regression analysis revealed no significant effect of BRCA1/2 mutation carriership on the RTDIs. No significant differences were found in the percentages of patients presenting with febrile neutropenia, having a delay in chemotherapy administration or switching to an altered chemotherapy regimen. Additionally, the odds ratios showed no significant effect of BRCA1/2 mutation carriership on the secondary outcome variables. (Neo)adjuvant chemotherapy-related toxicity was not different between BRCA1/2-associated and sporadic breast cancer patients suggesting that the DNA damage repair mechanism of non-cancer cells

  9. Documentation of chemotherapy infusion preparation costs in academic- and community-based oncology practices.

    PubMed

    Brixner, Diana I; Oderda, Gary M; Nickman, Nancy A; Beveridge, Roy; Jorgenson, James A

    2006-03-01

    Significant changes in Medicare reimbursement for outpatient oncology services were proposed as part of the Medicare Modernization Act of 2003. The purpose of this study was to identify the "true cost" associated with drug-related handling for the preparation and delivery of chemotherapy doses to estimate the impact of changing reimbursement schema by Medicare. Two academic medical outpatient infusion centers and 2 community cancer centers provided data used to estimate all costs (excluding drug cost) associated with the preparation of chemotherapy doses. The data included both fixed costs (drug storage, space, equipment, and information resources) and variable costs (insurance management, inventory, waste management, pharmacy staff payroll, supplies, and shipping). The average cost for the preparation of chemotherapy doses across all sites was dollar 34.27 (range, dollar 32.08-dollar 41.23). A time-and-motion study was also performed to determine what tasks were conducted by pharmacy staff and how much time was spent in the preparation of the top 15 chemotherapeutic drugs and regimens used in the 4 sites. Data from the 4 centers was projected to show that if 3,990,495 million chemotherapy infusions were administered to a national Medicare population in 2003, when multiplied by the average cost of preparation for infusions determined by the current study (dollar 34.27), the estimated total annual cost to Medicare for chemotherapy preparation by pharmacists is dollar 136,754,263.65. The pharmacists spent most of their days (90% or more) performing tasks directly related to the preparation of these agents. These data provide scientific support for the consideration of appropriate reimbursement for chemotherapy services provided by pharmacists to Medicare beneficiaries. PMID:16507268

  10. A Significant Statistical Advancement on the Predictive Values of ERCC1 Polymorphisms for Clinical Outcomes of Platinum-Based Chemotherapy in Non-Small Cell Lung Cancer: An Updated Meta-Analysis

    PubMed Central

    Han, Yali; Liu, Jie; Sun, Meili; Zhang, Zongpu; Liu, Chuanyong; Sun, Yuping

    2016-01-01

    Background. There is no definitive conclusion so far on the predictive values of ERCC1 polymorphisms for clinical outcomes of platinum-based chemotherapy in non-small cell lung cancer (NSCLC). We updated this meta-analysis with an expectation to obtain some statistical advancement on this issue. Methods. Relevant studies were identified by searching MEDLINE, EMBASE databases from inception to April 2015. Primary outcomes included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). All analyses were performed using the Review Manager version 5.3 and the Stata version 12.0. Results. A total of 33 studies including 5373 patients were identified. ERCC1 C118T and C8092A could predict both ORR and OS for platinum-based chemotherapy in Asian NSCLC patients (CT + TT versus CC, ORR: OR = 0.80, 95% CI = 0.67–0.94; OS: HR = 1.24, 95% CI = 1.01–1.53) (CA + AA versus CC, ORR: OR = 0.76, 95% CI = 0.60–0.96; OS: HR = 1.37, 95% CI = 1.06–1.75). Conclusions. Current evidence strongly indicated the prospect of ERCC1 C118T and C8092A as predictive biomarkers for platinum-based chemotherapy in Asian NSCLC patients. However, the results should be interpreted with caution and large prospective studies are still required to further investigate these findings. PMID:27057082

  11. The addition of gemtuzumab ozogamicin to chemotherapy in adult patients with acute myeloid leukemia.

    PubMed

    Kell, Jonathan

    2016-04-01

    The treatment of acute myeloid leukaemia has remained largely unchanged for the last 30 years since the advent of combination chemotherapy with cytarabine arabinoside and daunorubicin with remission rates around 70% but with long term survival still only around 40% in young adults. Doses of chemotherapy have been pushed to the limit of toxicity. Gemtuzumab ozogamicin allows additional chemotherapy to be delivered to the leukaemic cells without significantly adding to toxicity since the active agent is coupled to a monoclonal anti-CD33 antibody. It was approved by the FDA in 2000 for the treatment of elderly patients with relapsed CD33 positive AML at a dose of 9mg/m(2) on two days two weeks apart. Almost at once, questions were raised about its safety, with a particular liver signal, and it was voluntarily withdrawn from practice in 2010. Many groups have been examining the role of gemtuzumab ozogamicin in combination with chemotherapy, usually at lower doses than originally recommended, with varying degrees of success and toxicity and gemtuzumab ozogamicin is now entering a period of rehabilitation. Currently it is only commercially available in Japan although it is currently also available in the UK Bloodwise AML18 study. PMID:26942450

  12. [Prostate cancer and chemotherapy].

    PubMed

    Gravis, Gwenaelle; Salem, Naji; Bladou, Franck; Viens, Patrice

    2007-07-01

    Androgen deprivation in patients with metastatic prostate cancer produces palliation of symptoms, PSA decrease and tumoral regression in most patients. After a brief period of disease regression lasting 18 to 24 months nearly all pts will progress to androgen independence disease (HRPC) with progressive clinical deterioration and ultimately death. Chemotherapy with mitoxantrone has been shown to palliate symptoms but did not extend survival. Two large randomized trials showed a survival benefit for pts with HRPC treated with docetaxel with a reduction risk of death by 21-24%, and significant improvement in palliation of symptoms and quality of life. New agents targeting angiogenesis, apoptosis, signal transduction pathway, used alone or in combination with docetaxel currently are under trial in an attempt to provide much needed improvements in outcome. Questions remains in suspend when and who need to be treated, earlier, in high risk as in adjuvant setting? Current data have demonstrated that neoadjuvant or adjuvant chemotherapy is relatively safe and feasible. Further investigation through prospective randomize trials is critical to define the precise role of this modality in high risk populations. PMID:17845990

  13. Netupitant/Palonosetron: A Review in the Prevention of Chemotherapy-Induced Nausea and Vomiting.

    PubMed

    Keating, Gillian M

    2015-12-01

    An oral fixed combination of netupitant/palonosetron (NEPA; Akynzeo(®)) is available for use in the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV). Netupitant is a highly selective neurokinin-1 receptor antagonist and palonosetron is a serotonin 5-HT3 receptor antagonist with a distinct pharmacological profile. Complete response rates during the delayed, acute and overall phases were significantly higher with single-dose netupitant 300 mg plus palonosetron 0.5 mg than with single-dose palonosetron 0.5 mg in cycle 1 of cisplatin-based highly emetogenic chemotherapy (HEC) in a phase II trial and with single-dose netupitant/palonosetron 300/0.5 mg than with single-dose palonosetron 0.5 mg in cycle 1 of anthracycline-cyclophosphamide (AC) moderately emetogenic chemotherapy (MEC) in a phase III trial; the greater efficacy of netupitant/palonosetron was maintained over repeated cycles of AC MEC in the phase III trial. In another phase III trial, netupitant/palonosetron 300/0.5 mg was effective over repeated cycles of non-AC MEC or HEC. Netupitant/palonosetron was well tolerated, with no cardiac safety concerns. The convenience of administering netupitant/palonosetron as a single dose in a fixed combination has the potential to improve adherence to CINV prevention guidelines. In conclusion, netupitant/palonosetron is an important option to consider in the prevention of acute and delayed CINV in patients receiving MEC or HEC. PMID:26613606

  14. [Treatment of advanced ovarian carcinoma: surgery before chemotherapy or chemotherapy before surgery?].

    PubMed

    Piura, Benjamin

    2014-09-01

    The standard of care for advanced epithelial ovarian carcinoma has been primary surgery aspiring for optimal debulking followed by adjuvant chemotherapy. A significant survival advantage has been demonstrated in women having optimal debulking at primary surgery compared to women having less than optimal debulking at primary surgery. With the advent of efficient chemotherapy for ovarian carcinoma (combination of platinum and taxan), the administration of several courses of chemotherapy before surgery (neoadjuvant chemotherapy) has been established as a method for reducing the intra-abdominal tumor burden and, thereby, increasing the probability of optimal debulking at surgery which is usually performed in the interval between course no. 3 and no. 4 of chemotherapy (interval surgery). Higher rates of optimal debulking, Lower rates of surgical complications, but no differences in survival, have been demonstrated in women having chemotherapy before surgery compared to women having surgery before chemotherapy. Obviously, the method of neoadjuvant chemotherapy is the treatment of choice for women in whom the clinical evaluation indicates that there is no high probability of optimal debulking at primary surgery. Nevertheless, there has been a debate on whether or not the method of neoadjuvant chemotherapy should also be applied for women in whom the clinical evaluation indicates that they are fit for optimal debulking at primary surgery. There is a need for more prospective studies to evaluate the role of neoadjuvant chemotherapy in the treatment of ovarian carcinoma. PMID:25417488

  15. [Treatment of advanced ovarian carcinoma: surgery before chemotherapy or chemotherapy before surgery?............... ].

    PubMed

    Piura, Benjamin

    2014-09-01

    The standard of care for advanced epithelial ovarian carcinoma has been primary surgery aspiring for optimal debulking followed by adjuvant chemotherapy. A significant survival advantage has been demonstrated in women having optimal debulking at primary surgery compared to women having less than optimal debulking at primary surgery. With the advent of efficient chemotherapy for ovarian carcinoma (combination of platinum and taxan), the administration of several courses of chemotherapy before surgery (neoadjuvant chemotherapy) has been established as a method for reducing the intra-abdominal tumor burden and, thereby, increasing the probability of optimal debulking at surgery which is usually performed in the interval between course no. 3 and no. 4 of chemotherapy (interval surgery). Higher rates of optimal debulking, Lower rates of surgical complications, but no differences in survival, have been demonstrated in women having chemotherapy before surgery compared to women having surgery before chemotherapy. Obviously, the method of neoadjuvant chemotherapy is the treatment of choice for women in whom the clinical evaluation indicates that there is no high probability of optimal debulking at primary surgery. Nevertheless, there has been a debate on whether or not the method of neoadjuvant chemotherapy should also be applied for women in whom the clinical evaluation indicates that they are fit for optimal debulking at primary surgery. There is a need for more prospective studies to evaluate the role of neoadjuvant chemotherapy in the treatment of ovarian carcinoma. PMID:25507216

  16. Dexamethasone, carmustine, etoposide, cytarabine, and melphalan (dexa-BEAM) followed by high-dose chemotherapy and stem cell rescue--a highly effective regimen for patients with refractory or relapsed indolent lymphoma.

    PubMed

    Josting, A; Reiser, M; Wickramanayake, P D; Rueffer, U; Draube, A; Söhngen, D; Tesch, H; Wolf, J; Diehl, V; Engert, A

    2000-03-01

    We performed a phase II study to determine the efficacy of maximal cytoreductive therapy with up to five cycles of Dexa-BEAM (dexamethasone, carmustine [BCNU], etoposide, cytarabine, and melphalan) followed by high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) for patients with advanced relapsed or refractory indolent lymphoma. Thirty-two patients with primary refractory or relapsed indolent lymphoma were treated with the Dexa-BEAM regimen. Thirteen patients had primary refractory disease, 4 patients partial remission, and 15 patients first or subsequent relapse. Patients achieving PR or CR received HDCT with ASCT. The conditioning regimen used was BEAM (carmustine [BCNU], etoposide, cytarabine, and melphalan). Twenty-two patients responded to Dexa-BEAM resulting in a response rate of 78%. Maximum response was observed after 3.2 (range 2-5) courses. One patient with progressive disease died in septic shock during neutropenia. Nineteen patients with partial or complete remission after Dexa-BEAM received HDCT. Hematopoietic stem cells (HSC) were collected after two cycles of Dexa-BEAM. The median number of CD34+ HSC reinfused was 3.1 x 10(6)/kg (range 1.6-8.2 x 10(6)/kg). There was no transplantation-related death. All patients receiving HDCT achieved complete remission. Overall survival (OS) and freedom from treatment failure (FFTF) for all patients are estimated to be 68% and 65% at two years, respectively. With a mean follow-up of 20 months (range 8-42 months), 16/19 patients receiving HDCT are in continuous complete remission. The Dexa-BEAM regimen is effective in overcoming drug resistance in patients with indolent lymphoma who failed to respond to conventional treatment or who relapsed. The CR rate of 100% of those patients receiving HDCT and ASCT after maximal cytoreductive treatment with Dexa-BEAM suggests the use of HDCT at the time of maximal response. PMID:10721775

  17. Chemotherapy for intraperitoneal use: a review of hyperthermic intraperitoneal chemotherapy and early post-operative intraperitoneal chemotherapy

    PubMed Central

    McPartland, Sarah; Detelich, Danielle; Saif, Muhammad Wasif

    2016-01-01

    Peritoneal spread of tumors is a major problem in cancer management. Patients develop a marked deterioration in quality of life and shortened survival. This is in part due to bowel obstructions, marked ascites, and overall increase debilitation. Standard medical management has shown to be inadequate for the treatment of these problems. Surgery can palliate symptoms, however, it is unable to be complete at the microscopic level by a significant spillage of tumor cells throughout the abdomen. Chemotherapy can have some improvement in symptoms however it is short lived due to poor penetration into the peritoneal cavity. The role of intraperitoneal chemotherapy is to maximize tumor penetration and optimize cell death while minimizing systemic toxicity. Hyperthermic intraperitoneal chemotherapy (HIPEC) and early post-operative intraperitoneal chemotherapy (EPIC) are two treatment methods that serve this role and have been shown to improve survival. This review will discuss different chemotherapies used for both of these treatment options. PMID:26941983

  18. Chemotherapy for intraperitoneal use: a review of hyperthermic intraperitoneal chemotherapy and early post-operative intraperitoneal chemotherapy.

    PubMed

    Goodman, Martin D; McPartland, Sarah; Detelich, Danielle; Saif, Muhammad Wasif

    2016-02-01

    Peritoneal spread of tumors is a major problem in cancer management. Patients develop a marked deterioration in quality of life and shortened survival. This is in part due to bowel obstructions, marked ascites, and overall increase debilitation. Standard medical management has shown to be inadequate for the treatment of these problems. Surgery can palliate symptoms, however, it is unable to be complete at the microscopic level by a significant spillage of tumor cells throughout the abdomen. Chemotherapy can have some improvement in symptoms however it is short lived due to poor penetration into the peritoneal cavity. The role of intraperitoneal chemotherapy is to maximize tumor penetration and optimize cell death while minimizing systemic toxicity. Hyperthermic intraperitoneal chemotherapy (HIPEC) and early post-operative intraperitoneal chemotherapy (EPIC) are two treatment methods that serve this role and have been shown to improve survival. This review will discuss different chemotherapies used for both of these treatment options. PMID:26941983

  19. Protection against chemotherapy-induced alopecia: targeting ATP-binding cassette transporters in the hair follicle?

    PubMed

    Haslam, Iain S; Pitre, Aaron; Schuetz, John D; Paus, Ralf

    2013-11-01

    Currently, efficacious treatments for chemotherapy-induced alopecia (hair loss) are lacking, and incidences of permanent hair loss following high-dose chemotherapy are on the increase. In this article, we describe mechanisms by which the pharmacological defense status of the hair follicle might be enhanced, thereby reducing the accumulation of cytotoxic cancer drugs and preventing or reducing hair loss and damage. We believe this could be achieved via the selective increase in ATP-binding cassette (ABC) transporter expression within the hair follicle epithelium, following application of topical agonists for regulatory nuclear receptors. Clinical application would require the development of hair follicle-targeted formulations, potentially utilizing nanoparticle technology. This novel approach has the potential to yield entirely new therapeutic options for the treatment and management of chemotherapy-induced alopecia, providing significant psychological and physical benefit to cancer patients. PMID:24100054

  20. Schedule-Dependent Antiangiogenic and Cytotoxic Effects of Chemotherapy on Vascular Endothelial and Retinoblastoma Cells

    PubMed Central

    Winter, Ursula; Mena, Hebe A.; Negrotto, Soledad; Arana, Eloisa; Pascual-Pasto, Guillem; Laurent, Viviana; Suñol, Mariona; Chantada, Guillermo L.; Carcaboso, Angel M.; Schaiquevich, Paula

    2016-01-01

    Current treatment of retinoblastoma involves using the maximum dose of chemotherapy that induces tumor control and is tolerated by patients. The impact of dose and schedule on the cytotoxicity of chemotherapy has not been studied. Our aim was to gain insight into the cytotoxic and antiangiogenic effect of the treatment scheme of chemotherapy used in retinoblastoma by means of different in vitro models and to evaluate potential effects on multi-drug resistance proteins. Two commercial and two patient-derived retinoblastoma cell types and two human vascular endothelial cell types were exposed to increasing concentrations of melphalan or topotecan in a conventional (single exposure) or metronomic (7-day continuous exposure) treatment scheme. The concentration of chemotherapy causing a 50% decrease in cell proliferation (IC50) was determined by MTT and induction of apoptosis was evaluated by flow cytometry. Expression of ABCB1, ABCG2 and ABCC1 after conventional or metronomic treatments was assessed by RT-qPCR. We also evaluated the in vivo response to conventional (0.6 mg/kg once a week for 2 weeks) and metronomic (5 days a week for 2 weeks) topotecan in a retinoblastoma xenograft model. Melphalan and topotecan were cytotoxic to both retinoblastoma and endothelial cells after conventional and metronomic treatments. A significant decrease in the IC50 (median, 13-fold; range: 3–23) was observed following metronomic chemotherapy treatment in retinoblastoma and endothelial cell types compared to conventional treatment (p<0.05). Metronomic topotecan or melphalan significantly inhibited in vitro tube formation in HUVEC and EPC compared to vehicle-treated cells (p<0.05). Both treatment schemes induced apoptosis and/or necrosis in all cell models. No significant difference was observed in the expression of ABCB1, ABCC1 or ABCG2 when comparing cells treated with melphalan or topotecan between treatment schedules at the IC50 or with control cells (p>0.05). In mice, continuous

  1. Schedule-Dependent Antiangiogenic and Cytotoxic Effects of Chemotherapy on Vascular Endothelial and Retinoblastoma Cells.

    PubMed

    Winter, Ursula; Mena, Hebe A; Negrotto, Soledad; Arana, Eloisa; Pascual-Pasto, Guillem; Laurent, Viviana; Suñol, Mariona; Chantada, Guillermo L; Carcaboso, Angel M; Schaiquevich, Paula

    2016-01-01

    Current treatment of retinoblastoma involves using the maximum dose of chemotherapy that induces tumor control and is tolerated by patients. The impact of dose and schedule on the cytotoxicity of chemotherapy has not been studied. Our aim was to gain insight into the cytotoxic and antiangiogenic effect of the treatment scheme of chemotherapy used in retinoblastoma by means of different in vitro models and to evaluate potential effects on multi-drug resistance proteins. Two commercial and two patient-derived retinoblastoma cell types and two human vascular endothelial cell types were exposed to increasing concentrations of melphalan or topotecan in a conventional (single exposure) or metronomic (7-day continuous exposure) treatment scheme. The concentration of chemotherapy causing a 50% decrease in cell proliferation (IC50) was determined by MTT and induction of apoptosis was evaluated by flow cytometry. Expression of ABCB1, ABCG2 and ABCC1 after conventional or metronomic treatments was assessed by RT-qPCR. We also evaluated the in vivo response to conventional (0.6 mg/kg once a week for 2 weeks) and metronomic (5 days a week for 2 weeks) topotecan in a retinoblastoma xenograft model. Melphalan and topotecan were cytotoxic to both retinoblastoma and endothelial cells after conventional and metronomic treatments. A significant decrease in the IC50 (median, 13-fold; range: 3-23) was observed following metronomic chemotherapy treatment in retinoblastoma and endothelial cell types compared to conventional treatment (p<0.05). Metronomic topotecan or melphalan significantly inhibited in vitro tube formation in HUVEC and EPC compared to vehicle-treated cells (p<0.05). Both treatment schemes induced apoptosis and/or necrosis in all cell models. No significant difference was observed in the expression of ABCB1, ABCC1 or ABCG2 when comparing cells treated with melphalan or topotecan between treatment schedules at the IC50 or with control cells (p>0.05). In mice, continuous

  2. Anatomy-Based Inverse Planning Simulated Annealing Optimization in High-Dose-Rate Prostate Brachytherapy: Significant Dosimetric Advantage Over Other Optimization Techniques

    SciTech Connect

    Jacob, Dayee Raben, Adam; Sarkar, Abhirup; Grimm, Jimm; Simpson, Larry

    2008-11-01

    Purpose: To perform an independent validation of an anatomy-based inverse planning simulated annealing (IPSA) algorithm in obtaining superior target coverage and reducing the dose to the organs at risk. Method and Materials: In a recent prostate high-dose-rate brachytherapy protocol study by the Radiation Therapy Oncology Group (0321), our institution treated 20 patients between June 1, 2005 and November 30, 2006. These patients had received a high-dose-rate boost dose of 19 Gy to the prostate, in addition to an external beam radiotherapy dose of 45 Gy with intensity-modulated radiotherapy. Three-dimensional dosimetry was obtained for the following optimization schemes in the Plato Brachytherapy Planning System, version 14.3.2, using the same dose constraints for all the patients treated during this period: anatomy-based IPSA optimization, geometric optimization, and dose point optimization. Dose-volume histograms were generated for the planning target volume and organs at risk for each optimization method, from which the volume receiving at least 75% of the dose (V{sub 75%}) for the rectum and bladder, volume receiving at least 125% of the dose (V{sub 125%}) for the urethra, and total volume receiving the reference dose (V{sub 100%}) and volume receiving 150% of the dose (V{sub 150%}) for the planning target volume were determined. The dose homogeneity index and conformal index for the planning target volume for each optimization technique were compared. Results: Despite suboptimal needle position in some implants, the IPSA algorithm was able to comply with the tight Radiation Therapy Oncology Group dose constraints for 90% of the patients in this study. In contrast, the compliance was only 30% for dose point optimization and only 5% for geometric optimization. Conclusions: Anatomy-based IPSA optimization proved to be the superior technique and also the fastest for reducing the dose to the organs at risk without compromising the target coverage.

  3. [Dose individualization for carboplatin in cancer chemotherapy].

    PubMed

    Oudard, S; Lauraine, E P

    1997-06-01

    The aim of optimizing drug therapy for an individual patient is to maximize the likelihood of a desired therapeutic effect and to minimize the likelihood of toxicity. The excellent correlations between renal function and carboplatin total body clearance and between carboplatin area under the plasma concentration by time curve and thrombocytopenia allow calculation by Chatelut formula of carboplatin dosage. PMID:9295872

  4. Chemotherapy in Prostate Cancer.

    PubMed

    Hurwitz, Michael

    2015-10-01

    For approximately a decade, chemotherapy has been shown to prolong life in patients with metastatic castration-resistant prostate cancer (mCRPC). Since that time, however, only two agents have proven to prolong life (docetaxel and cabazitaxel). However, in the last year, the addition of chemotherapy to primary hormonal therapy became a standard of care for high-volume castration-sensitive metastatic disease. Here I will review current prostate cancer chemotherapies, mechanisms of resistance to those therapies, and ongoing clinical studies of chemotherapy combinations and novel chemotherapeutics. PMID:26216506

  5. High-dose electron beam sterilization of soft-tissue grafts maintains significantly improved biomechanical properties compared to standard gamma treatment.

    PubMed

    Hoburg, A; Keshlaf, S; Schmidt, T; Smith, M; Gohs, U; Perka, C; Pruss, A; Scheffler, S

    2015-06-01

    Allografts have gained increasing popularity in anterior cruciate ligament (ACL) reconstruction. However, one of the major concerns regarding allografts is the possibility of disease transmission. Electron beam (Ebeam) and Gamma radiation have been proven to be successful in sterilization of medical products. In soft tissue sterilization high dosages of gamma irradiation have been shown to be detrimental to biomechanical properties of grafts. Therefore, it was the objective of this study to compare the biomechanical properties of human bone-patellar tendon-bone (BPTB) grafts after ebeam with standard gamma irradiation at medium (25 kGy) and high doses (34 kGy). We hypothesized that the biomechanical properties of Ebeam irradiated grafts would be superior to gamma irradiated grafts. Paired 10 mm-wide human BPTB grafts were harvested from 20 donors split into four groups following irradiation with either gamma or Ebeam (each n = 10): (A) Ebeam 25 kGy, (B) Gamma 25 kGy, (C) Ebeam 34 kGy (D) Gamma 34 kGy and ten non-irradiated BPTB grafts were used as controls. All grafts underwent biomechanical testing which included preconditioning (ten cycles, 0-20 N); cyclic loading (200 cycles, 20-200 N) and a load-to-failure (LTF) test. Stiffness of non-irradiated controls (199.6 ± 59.1 N/mm) and Ebeam sterilized grafts did not significantly differ (152.0 ± 37.0 N/mm; 192.8 ± 58.0 N/mm), while Gamma-irradiated grafts had significantly lower stiffness than controls at both irradiation dosages (25 kGy: 126.1 ± 45.4 N/mm; 34 kGy: 170.6 ± 58.2 N/mm) (p < 0.05). Failure loads at 25 kGy were significantly lower in the gamma group (1,009 ± 400 N), while the failure load was significantly lower in both study groups at high dose irradiation with 34 kGy (Ebeam: 1,139 ± 445 N, Gamma: 1,073 ± 617 N) compared to controls (1,741 ± 304 N) (p < 0.05). Creep was significantly larger in the gamma irradiated groups (25 kGy: 0.96 ± 1.34 mm; 34 kGy: 1.06 ± 0.58 mm) than in the Ebeam (25 k

  6. Inhaled chemotherapy in lung cancer: future concept of nanomedicine

    PubMed Central

    Zarogoulidis, Paul; Chatzaki, Ekaterini; Porpodis, Konstantinos; Domvri, Kalliopi; Hohenforst-Schmidt, Wolfgang; Goldberg, Eugene P; Karamanos, Nikos; Zarogoulidis, Konstantinos

    2012-01-01

    Regional chemotherapy was first used for lung cancer 30 years ago. Since then, new methods of drug delivery and pharmaceuticals have been investigated in vitro, and in animals and humans. An extensive review of drug delivery systems, pharmaceuticals, patient monitoring, methods of enhancing inhaled drug deposition, safety and efficacy, and also additional applications of inhaled chemotherapy and its advantages and disadvantages are presented. Regional chemotherapy to the lung parenchyma for lung cancer is feasible and efficient. Safety depends on the chemotherapy agent delivered to the lungs and is dose-dependent and time-dependent. Further evaluation is needed to provide data regarding early lung cancer stages, and whether regional chemotherapy can be used as neoadjuvant or adjuvant treatment. Finally, inhaled chemotherapy could one day be administered at home with fewer systemic adverse effects. PMID:22619512

  7. The Interplay of Immunotherapy and Chemotherapy: Harnessing Potential Synergies

    PubMed Central

    Emens, Leisha A.; Middleton, Gary

    2016-01-01

    Although cancer chemotherapy has historically been considered immune suppressive, it is now accepted that certain chemotherapies can augment tumor immunity. The recent success of immune checkpoint inhibitors has renewed interest in immunotherapies, and in combining them with chemotherapy to achieve additive or synergistic clinical activity. Two major ways that chemotherapy promotes tumor immunity are by inducing immunogenic cell death as part of its intended therapeutic effect, and by disrupting strategies that tumors use to evade immune recognition. This second strategy in particular is dependent on the drug, its dose, and the schedule of chemotherapy administration in relation to antigen exposure or release. In this Cancer Immunology at the Crossroads article we focus on cancer vaccines and immune checkpoint blockade as a forum for reviewing preclinical and clinical data demonstrating the interplay between immunotherapy and chemotherapy. PMID:25941355

  8. Update on Adjuvant Chemotherapy for Early Breast Cancer

    PubMed Central

    Rampurwala, Murtuza M; Rocque, Gabrielle B; Burkard, Mark E

    2014-01-01

    Breast cancer is the second most common cancer in women worldwide. Although most women are diagnosed with early breast cancer, a substantial number recur due to persistent micro-metastatic disease. Systemic adjuvant chemotherapy improves outcomes and has advanced from first-generation regimens to modern dose-dense combinations. Although chemotherapy is the cornerstone of adjuvant therapy, new biomarkers are identifying patients who can forego such treatment. Neo-adjuvant therapy is a promising platform for drug development, but investigators should recognize the limitations of surrogate endpoints and clinical trials. Previous decades have focused on discovering, developing, and intensifying adjuvant chemotherapy. Future efforts should focus on customizing therapy and reducing chemotherapy for patients unlikely to benefit. In some cases, it may be possible to replace chemotherapy with treatments directed at specific genetic or molecular breast cancer subtypes. Yet, we anticipate that chemotherapy will remain a critical component of adjuvant therapy for years to come. PMID:25336961

  9. SU-E-J-28: Gantry Speed Significantly Affects Image Quality and Imaging Dose for 4D Cone-Beam Computed Tomography On the Varian Edge Platform

    SciTech Connect

    Santoso, A; Song, K; Gardner, S; Chetty, I; Wen, N

    2015-06-15

    Purpose: 4D-CBCT facilitates assessment of tumor motion at treatment position. We investigated the effect of gantry speed on 4D-CBCT image quality and dose using the Varian Edge On-Board Imager (OBI). Methods: A thoracic protocol was designed using a 125 kVp spectrum. Image quality parameters were obtained via 4D acquisition using a Catphan phantom with a gating system. A sinusoidal waveform was executed with a five second period and superior-inferior motion. 4D-CBCT scans were sorted into 4 and 10 phases. Image quality metrics included spatial resolution, contrast-to-noise ratio (CNR), uniformity index (UI), Hounsfield unit (HU) sensitivity, and RMS error (RMSE) of motion amplitude. Dosimetry was accomplished using Gafchromic XR-QA2 films within a CIRS Thorax phantom. This was placed on the gating phantom using the same motion waveform. Results: High contrast resolution decreased linearly from 5.93 to 4.18 lp/cm, 6.54 to 4.18 lp/cm, and 5.19 to 3.91 lp/cm for averaged, 4 phase, and 10 phase 4DCBCT volumes respectively as gantry speed increased from 1.0 to 6.0 degs/sec. CNRs decreased linearly from 4.80 to 1.82 as the gantry speed increased from 1.0 to 6.0 degs/sec, respectively. No significant variations in UIs, HU sensitivities, or RMSEs were observed with variable gantry speed. Ion chamber measurements compared to film yielded small percent differences in plastic water regions (0.1–9.6%), larger percent differences in lung equivalent regions (7.5–34.8%), and significantly larger percent differences in bone equivalent regions (119.1–137.3%). Ion chamber measurements decreased from 17.29 to 2.89 cGy with increasing gantry speed from 1.0 to 6.0 degs/sec. Conclusion: Maintaining technique factors while changing gantry speed changes the number of projections used for reconstruction. Increasing the number of projections by decreasing gantry speed decreases noise, however, dose is increased. The future of 4DCBCT’s clinical utility relies on further

  10. WE-D-BRE-04: Modeling Optimal Concurrent Chemotherapy Schedules

    SciTech Connect

    Jeong, J; Deasy, J O

    2014-06-15

    Purpose: Concurrent chemo-radiation therapy (CCRT) has become a more common cancer treatment option with a better tumor control rate for several tumor sites, including head and neck and lung cancer. In this work, possible optimal chemotherapy schedules were investigated by implementing chemotherapy cell-kill into a tumor response model of RT. Methods: The chemotherapy effect has been added into a published model (Jeong et al., PMB (2013) 58:4897), in which the tumor response to RT can be simulated with the effects of hypoxia and proliferation. Based on the two-compartment pharmacokinetic model, the temporal concentration of chemotherapy agent was estimated. Log cell-kill was assumed and the cell-kill constant was estimated from the observed increase in local control due to concurrent chemotherapy. For a simplified two cycle CCRT regime, several different starting times and intervals were simulated with conventional RT regime (2Gy/fx, 5fx/wk). The effectiveness of CCRT was evaluated in terms of reduction in radiation dose required for 50% of control to find the optimal chemotherapy schedule. Results: Assuming the typical slope of dose response curve (γ50=2), the observed 10% increase in local control rate was evaluated to be equivalent to an extra RT dose of about 4 Gy, from which the cell-kill rate of chemotherapy was derived to be about 0.35. Best response was obtained when chemotherapy was started at about 3 weeks after RT began. As the interval between two cycles decreases, the efficacy of chemotherapy increases with broader range of optimal starting times. Conclusion: The effect of chemotherapy has been implemented into the resource-conservation tumor response model to investigate CCRT. The results suggest that the concurrent chemotherapy might be more effective when delayed for about 3 weeks, due to lower tumor burden and a larger fraction of proliferating cells after reoxygenation.

  11. Mechanisms of chemotherapy-induced behavioral toxicities

    PubMed Central

    Vichaya, Elisabeth G.; Chiu, Gabriel S.; Krukowski, Karen; Lacourt, Tamara E.; Kavelaars, Annemieke; Dantzer, Robert; Heijnen, Cobi J.; Walker, Adam K.

    2015-01-01

    While chemotherapeutic agents have yielded relative success in the treatment of cancer, patients are often plagued with unwanted and even debilitating side-effects from the treatment which can lead to dose reduction or even cessation of treatment. Common side effects (symptoms) of chemotherapy include (i) cognitive deficiencies such as problems with attention, memory and executive functioning; (ii) fatigue and motivational deficit; and (iii) neuropathy. These symptoms often develop during treatment but can remain even after cessation of chemotherapy, severely impacting long-term quality of life. Little is known about the underlying mechanisms responsible for the development of these behavioral toxicities, however, neuroinflammation is widely considered to be one of the major mechanisms responsible for chemotherapy-induced symptoms. Here, we critically assess what is known in regards to the role of neuroinflammation in chemotherapy-induced symptoms. We also argue that, based on the available evidence, neuroinflammation is unlikely the only mechanism involved in the pathogenesis of chemotherapy-induced behavioral toxicities. We evaluate two other putative candidate mechanisms. To this end we discuss the mediating role of damage-associated molecular patterns (DAMPs) activated in response to chemotherapy-induced cellular damage. We also review the literature with respect to possible alternative mechanisms such as a chemotherapy-induced change in the bioenergetic status of the tissue involving changes in mitochondrial function in relation to chemotherapy-induced behavioral toxicities. Understanding the mechanisms that underlie the emergence of fatigue, neuropathy, and cognitive difficulties is vital to better treatment and long-term survival of cancer patients. PMID:25954147

  12. Postoperative Chemotherapy Followed by Conformal Concomitant Chemoradiotherapy in High-Risk Gastric Cancer

    SciTech Connect

    Quero, Laurent; Bouchbika, Zineb; Kouto, Honorine; Baruch-Hennequin, Valerie; Gornet, Jean-Marc; Munoz, Nicolas; Cojean-Zelek, Isabelle; Houdart, Remi; Panis, Yves; Valleur, Patrice; Aparicio, Thomas; Maylin, Claude; Hennequin, Christophe

    2012-06-01

    Purpose: To analyze the efficacy, toxicity, and pattern of relapse after adjuvant cisplatin-based chemotherapy followed by three-dimensional irradiation and concomitant LV5FU2 chemotherapy (high-dose leucovorin and 5-fluorouracil bolus plus continuous infusion) in the treatment of completely resected high-risk gastric cancer. Methods and Materials: This was a retrospective analysis of 52 patients with high-risk gastric cancer initially treated by total/partial gastrectomy and lymphadenectomy between January 2002 and June 2007. Median age was 54 years (range, 36-75 years). Postoperative treatment consisted of 5-fluorouracil and cisplatin chemotherapy. Adjuvant chemotherapy was followed by three-dimensional conformal radiotherapy in the tumor bed and regional lymph nodes at 4500 cGy/25 fractions in association with concomitant chemotherapy. Concomitant chemotherapy consisted of a 2-h infusion of leucovorin (200 mg/m Superscript-Two ) followed by a bolus of 5-fluorouracil (400 mg/m Superscript-Two ) and then a 44-h continuous infusion of 5-fluorouracil (2400-3600 mg/m Superscript-Two ) given every 14 days, for three cycles (LV5FU2 protocol). Results: Five-year overall and disease-free survival were 50% and 48%, respectively. Distant metastases and peritoneal spread were the most frequent sites of relapse (37% each). After multivariate analysis, only pathologic nodal status was significantly associated with disease-free and overall survival. Acute toxicities were essentially gastrointestinal and hematologic. One myocardial infarction and one pulmonary embolism were also reported. Eighteen patients had a radiotherapy program interruption because of acute toxicity. All patients but 2 have completed radiotherapy. Conclusion: Postoperative cisplatin-based chemotherapy followed by conformal radiotherapy in association with concurrent 5-fluorouracil seemed to be feasible and resulted in successful locoregional control.

  13. Prevention of chemotherapy-induced ovarian damage.

    PubMed

    Roness, Hadassa; Kashi, Oren; Meirow, Dror

    2016-01-01

    Recent advances in our understanding of the mechanisms underlying the impact of cytotoxic drugs on the ovary have opened up new directions for the protection of the ovary from chemotherapy-induced damage. These advances have spurred the investigation of pharmacological agents to prevent ovarian damage at the time of treatment. Prevention of ovarian damage and follicle loss would provide significant advantages over existing fertility preservation techniques. This manuscript reviews new methods for the prevention of chemotherapy-induced ovarian damage, including agents that act on the PI3K/PTEN/Akt follicle activation pathway, apoptotic pathways, the vascular system, and other potential methods of reducing chemotherapy-induced ovotoxicity. PMID:26677788

  14. Prognostic significance of S100A4 expression in stage II and III colorectal cancer: results from a population-based series and a randomized phase III study on adjuvant chemotherapy.

    PubMed

    Boye, Kjetil; Jacob, Havjin; Frikstad, Kari-Anne M; Nesland, Jahn M; Maelandsmo, Gunhild M; Dahl, Olav; Nesbakken, Arild; Flatmark, Kjersti

    2016-08-01

    Current clinical algorithms are unable to precisely predict which colorectal cancer patients would benefit from adjuvant chemotherapy, and there is a need for novel biomarkers to improve the selection of patients. The metastasis-promoting protein S100A4 predicts poor outcome in colorectal cancer, but whether it could be used to guide clinical decision making remains to be resolved. S100A4 expression was analyzed by immunohistochemistry in primary colorectal carcinomas from a consecutively collected, population-representative cohort and a randomized phase III study on adjuvant 5-fluorouracil/levamisole. Sensitivity to treatment with 5-fluorouracil in S100A4 knockdown cells was investigated using 2D and 3D cell culture assays. Strong nuclear expression of S100A4 was detected in 19% and 23% of the tumors in the two study cohorts, respectively. In both cohorts, nuclear immunoreactivity was associated with reduced relapse-free (P < 0.001 and P = 0.010) and overall survival (P = 0.046 and P = 0.006) in univariate analysis. In multivariate analysis, nuclear S100A4 was a predictor of poor relapse-free survival in the consecutive series (P = 0.002; HR 1.9), but not in the randomized study. Sensitivity to treatment with 5-fluorouracil was not affected by S100A4 expression in in vitro cell culture assays, and there was no indication from subgroup analyses in the randomized study that S100A4 expression was associated with increased benefit of adjuvant treatment with 5-fluorouracil/levamisole. The present study confirms that nuclear S100A4 expression is a negative prognostic biomarker in colorectal cancer, but the clinical utility in selection of patients for adjuvant fluoropyrimidine-based chemotherapy is limited. PMID:27273130

  15. Chemotherapy treatment decision making by professionals and older patients with cancer: a narrative review of the literature.

    PubMed

    Johnson, M

    2012-01-01

    This narrative review of the literature examines the issues influencing chemotherapy treatment of older patients with cancer. Increasing age is associated with physical, social and psychological changes, but the rate of change differs widely between people, such that chronological age is not a good determinant of fitness for treatment. Changes in old age can affect disease processes and treatments that are offered. Clinical trials suggest that older patients gain benefits from chemotherapy, but with increased toxicity profile. Dose reductions may be required, but the effect on outcome is not known. Adjuvant chemotherapy is likely to benefit patients with a life expectancy over 5 years, although mortality benefits become less pronounced with increasing age. Older patients want chemotherapy, as long as side effects do not reduce quality of life or ability to function independently. Older patients face barriers to communication with professionals, including sensory and memory problems and poorer health literacy. Patients should be assessed covering functional, physiological and socio-economic domains that identify significant comorbid disease and frailty, to ensure that planned chemotherapy is appropriate. Successful treatment of older patients with chemotherapy may require interventions to support them to ensure all patients who may derive benefit can undergo treatment, if they so wish. PMID:21955060

  16. Intensity-Modulated Radiation Therapy With Concurrent Chemotherapy as Preoperative Treatment for Localized Gastric Adenocarcinoma

    SciTech Connect

    Chakravarty, Twisha; Crane, Christopher H.; Ajani, Jaffer A.; Mansfield, Paul F.; Briere, Tina M.; Beddar, A. Sam; Mok, Henry; Reed, Valerie K.; Krishnan, Sunil; Delclos, Marc E.; Das, Prajnan

    2012-06-01

    Purpose: The goal of this study was to evaluate dosimetric parameters, acute toxicity, pathologic response, and local control in patients treated with preoperative intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy for localized gastric adenocarcinoma. Methods: Between November 2007 and April 2010, 25 patients with localized gastric adenocarcinoma were treated with induction chemotherapy, followed by preoperative IMRT and concurrent chemotherapy and, finally, surgical resection. The median radiation therapy dose was 45 Gy. Concurrent chemotherapy was 5-fluorouracil and oxaliplatin in 18 patients, capecitabine in 3, and other regimens in 4. Subsequently, resection was performed with total gastrectomy in 13 patients, subtotal gastrectomy in 7, and other surgeries in 5. Results: Target coverage, expressed as the ratio of the minimum dose received by 99% of the planning target volume to the prescribed dose, was a median of 0.97 (range, 0.92-1.01). The median V{sub 30} (percentage of volume receiving at least 30 Gy) for the liver was 26%; the median V{sub 20} (percentage of volume receiving at least 20 Gy) for the right and left kidneys was 14% and 24%, respectively; and the median V{sub 40} (percentage of volume receiving at least 40 Gy) for the heart was 18%. Grade 3 acute toxicity developed in 14 patients (56%), including dehydration in 10, nausea in 8, and anorexia in 5. Grade 4 acute toxicity did not develop in any patient. There were no significant differences in the rates of acute toxicity, hospitalization, or feeding tube use in comparison to those in a group of 50 patients treated with preoperative three-dimensional conformal radiation therapy with concurrent chemotherapy. R0 resection was obtained in 20 patients (80%), and pathologic complete response occurred in 5 (20%). Conclusions: Preoperative IMRT for gastric adenocarcinoma was well tolerated, accomplished excellent target coverage and normal structure sparing, and led to appropriate

  17. Outcomes for newly diagnosed patients with acute myeloid leukemia dosed on actual or adjusted body weight

    PubMed Central

    Bivona, Cory; Rockey, Michelle; Henry, Dave; Grauer, Dennis; Abhyankar, Sunil; Aljitawi, Omar; Ganguly, Siddhartha; McGuirk, Joseph; Singh, Anurag; Lin, Tara L.

    2015-01-01

    Purpose Data from solid tumor malignancies suggest that actual body weight (ABW) dosing improves overall outcomes. There is the potential to compromise efficacy when chemotherapy dosages are reduced, but the impact of dose adjustment on clinical response and toxicity in hematologic malignancies is unknown. The purpose of this study was to evaluate the outcomes of utilizing a percent of ABW for acute myeloid leukemia (AML) induction chemotherapy dosing. Methods This retrospective, single-center study included 146 patients who received 7 + 3 induction (cytarabine and anthracycline) for treatment of AML. Study design evaluated the relationship between percentage of ABW dosing and complete response (CR) rates in patients newly diagnosed with AML. Results Percentage of ABW dosing did not influence CR rates in patients undergoing induction chemotherapy for AML (p = 0.83); nor did it influence rate of death at 30 days or relapse at 6 months (p = 0.94). When comparing patients dosed at 90–100 % of ABW compared to <90 % ABW, CR rates were not significantly different in patients classified as poor risk (p = 0.907). All favorable risk category patients obtained CR. Conclusions Preemptive dose reductions for obesity did not influence CR rates for patients with AML undergoing induction chemotherapy and did not influence the composite endpoint of death at 30 days or disease relapse at 6 months. PMID:26231954

  18. Experimental chemotherapy and radiotherapy to paratesticular rhabdomyosarcoma

    SciTech Connect

    Motoyama, T.; Watanabe, H.; Watanabe, T.; Yamamoto, T.

    1989-01-01

    Experimental chemotherapy and radiotherapy were tried in transplanted tumors derived from a paratesticular embryonal rhabdomyosarcoma. There was no significant difference on the therapeutic effect between a combination chemotherapy composed of vincristine, actinomycin D and cyclophosphamide, so-called VAC regimen, and a single therapy of radiation. However, morphologic analyses suggest that VAC is effective in embryonal rhabdomyosarcomas in which undifferentiated rhabdomyoblasts predominate, while radiotherapy is preferable for those containing variously differentiated rhabdomyoblasts.

  19. Management of acute and delayed chemotherapy-induced nausea and vomiting: role of netupitant–palonosetron combination

    PubMed Central

    Janicki, Piotr K

    2016-01-01

    Purpose The purpose of this review is to summarize and discuss the recently published data (both original studies and reviews) on the oral medication NEPA, consisting of netupitant (a neurokinin-1 receptor antagonist [NK1RA], 300 mg dose) and palonosetron (5-hydroxytryptamine [serotonin or 5HT] type 3 receptor antagonist [5HT3RA], 0.5 mg dose), in the prevention of the acute and delayed nausea and vomiting in patients receiving highly or moderately emetogenic chemotherapy. Methods This review was based on the very limited number of available published trials consisting of two Phase III studies and one Phase II dose-selecting trial. Results These studies demonstrated some therapeutic benefits of NEPA over related chemotherapy-induced nausea and vomiting (CINV) prophylaxis management, as well as its beneficial safety profile. In particular, compared with single-dose 0.5 mg palonosetron, the complete response rates for all phases of CINV for the first cycle of highly emetogenic chemotherapy (with cisplatin), as well as anthracycline–cyclophosphamide-based moderately emetogenic chemotherapy, were significantly higher for single-dose NEPA. The high efficacy of NEPA in terms of prevention of CINV continued throughout repeated cycles of highly and moderately emetogenic therapies. Conclusion It is currently recommended that patients who are administered highly emetogenic chemotherapy regimens should obtain a three-drug combination consisting of NK1RA, 5HT3RA, and dexamethasone. The recently available oral combination of NEPA plus dexamethasone provides an additional pharmacological management option that could be considered in this scenario. PMID:27194913

  20. Virtual Reality: A Distraction Intervention for Chemotherapy

    PubMed Central

    Schneider, Susan M.; Hood, Linda E.

    2007-01-01

    Purpose/Objectives To explore virtual reality (VR) as a distraction intervention to relieve symptom distress in adults receiving chemotherapy treatments for breast, colon, and lung cancer. Design Crossover design in which participants served as their own control. Setting Outpatient clinic at a comprehensive cancer center in the southeastern United States. Sample 123 adults receiving initial chemotherapy treatments. Methods Participants were randomly assigned to receive the VR distraction intervention during one chemotherapy treatment and then received no intervention (control) during an alternate matched chemotherapy treatment. The Adapted Symptom Distress Scale–2, Revised Piper Fatigue Scale, and State Anxiety Inventory were used to measure symptom distress. The Presence Questionnaire and an open-ended questionnaire were used to evaluate the subjects’ VR experience. The influence of type of cancer, age, and gender on symptom outcomes was explored. Mixed models were used to test for differences in levels of symptom distress. Main Research Variables Virtual reality and symptom distress. Findings Patients had an altered perception of time (p < 0.001) when using VR, which validates the distracting capacity of the intervention. Evaluation of the intervention indicated that patients believed the head-mounted device was easy to use, they experienced no cybersickness, and 82% would use VR again. However, analysis demonstrated no significant differences in symptom distress immediately or two days following chemotherapy treatments. Conclusions Patients stated that using VR made the treatment seem shorter and that chemotherapy treatments with VR were better than treatments without the distraction intervention. However, positive experiences did not result in a decrease in symptom distress. The findings support the idea that using VR can help to make chemotherapy treatments more tolerable, but clinicians should not assume that use of VR will improve chemotherapy

  1. Nanoscale drug delivery for targeted chemotherapy.

    PubMed

    Xin, Yong; Huang, Qian; Tang, Jian-Qin; Hou, Xiao-Yang; Zhang, Pei; Zhang, Long Zhen; Jiang, Guan

    2016-08-28

    Despite significant improvements in diagnostic methods and innovations in therapies for specific cancers, effective treatments for neoplastic diseases still represent major challenges. Nanotechnology as an emerging technology has been widely used in many fields and also provides a new opportunity for the targeted delivery of cancer drugs. Nanoscale delivery of chemotherapy drugs to the tumor site is highly desirable. Recent studies have shown that nanoscale drug delivery systems not only have the ability to destroy cancer cells but may also be carriers for chemotherapy drugs. Some studies have demonstrated that delivery of chemotherapy via nanoscale carriers has greater therapeutic benefit than either treatment modality alone. In this review, novel approaches to nanoscale delivery of chemotherapy are described and recent progress in this field is discussed. PMID:27235607

  2. Chemotherapy of eyelid and peritorbital tumors.

    PubMed Central

    Luxenberg, M N; Guthrie, T H

    1985-01-01

    Eight patients with nine histologically proven BCC or SCC involving the eyelids and periorbital tissues were treated with systemic and/or local (iontophoresis) chemotherapy using cisplatin and doxorubicin. All patients had either refused surgery, would have required extensive procedures, or had medical problems contraindicating surgery. Systemic chemotherapy induced a CR or PR in eight of nine lesions. No patient has required maintenance chemotherapy and no significant toxic side effects were encountered. The length of follow-up ranges from 2 to 50 months. Iontophoretic therapy with cisplatin was used to treat five small foci of new, recurrent or persistent tumor(s) in three of these patients, and resulted in a partial response in all five lesions. Systemic or local chemotherapy offers an alternative to current standard forms of treatment for BCC and SCC in selected cases. Images FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 8 FIGURE 9 FIGURE 10 PMID:3832525

  3. [Treatment of multiple myeloma with high-dose chemotherapy and transplantation of autologous hematopoietic stem cells and subsequent maintenance therapy with interferon alfa-2b or interferon alfa 2b and dexamethasone. Report of the ongoing study of the "4W" Czech Myeloma Group].

    PubMed

    Adam, Z; Krejcí, M; Bacovský, J; Hejlová, N; Kuca, B; Svojgrová, M; Franková, H; Gumulec, J; Janca, J; Veprek, K; Januska, B; Lehanka, F; Rezek, Z; Praskac, P; Cahová, S; Vránová, M; Papajík, T; Králová, E; Novotná, J; Scudla, V; Koza, V; Drbal, J; Faber, E; Mareschová, I; Hájek, R

    1998-07-01

    We report our results with high-dose chemotherapy in previously untreated multiple myeloma patients (4 courses of VAD chemotherapy, collection of PBSC after priming with cyclophosphamide, 5 g/m2, high-dose chemotherapy with melphalan, 200 mg/m2). Second transplantation was indicated only for patients who did not achieve remission after the first high-dose therapy (paraprotein lower than 25% of the pretreatment value). For the second transplantation melphalan (200 mg/m2) with methylprednisolone (1.5 g for 5 days) were used as conditioning regimen. After high-dose therapy all patients were randomized into two arms of maintenance therapy: interferon alpha-2b or sequential maintenance therapy (interferon alpha-2b for 3 months followed after 4 week pause by 40 mg of dexamethasone days 1-4, 10-13 and 20-23. The administration of interferon alpha was resumed four weeks after the last dexamethasone for next three months. The maintenance therapy continued for 48 months or until the progression. Fifty-five patients were enrolled in the study from January 1996 to August 1997. Thirty-five patients have undergone the first transplantation and 57% of them reached complete remission. There were 10% of non-responders after the first high-dose regimen. The mean time to reach white blood cell count above 1 x 10(9)/L after the application of high dose melphalan and platelets more than 50 x 10(9)/L were 12.2 (range 6-16 days) and 12.4 (range 0-25 days), respectively. Grade 4 mucositis according to SWOG classification requiring total parenteral nutrition was presented in 40% of the patients. The mean number of 1 unit of platelets and 2 units of packed red blood cells transfusions were given within the posttransplant period. Early transplant related mortality was 3%. This paper describes the response and tolerance of each particular step of therapy. The follow-up has been too short to evaluate event-free and overall survivals. PMID:9748876

  4. Chemotherapy in metastatic retinoblastoma.

    PubMed

    Kingston, J E; Hungerford, J L; Plowman, P N

    1987-03-01

    Eleven children with metastatic retinoblastoma diagnosed during the period 1970-1984 were treated with chemotherapy. Short-term complete responses were observed in three children treated with a four-drug combination which included cisplatinum, and in one child treated with vincristine and cyclophosphamide. The median duration of survival of the 11 children receiving chemotherapy was nine months, whilst the median survival of 13 children with metastatic retinoblastoma who were not given chemotherapy was only 2.3 months (p = 0.06). This suggests that retinoblastoma is a chemosensitive tumour and therefore adjuvant chemotherapy may have a role in children with retinoblastoma who at diagnosis are thought to be at high risk of developing metastatic disease. PMID:3587892

  5. Chemotherapy (For Parents)

    MedlinePlus

    ... sample before beginning chemotherapy to evaluate kidney function. Giving your child plenty of fluids to drink will ... eating, after using the bathroom, and after touching animals. They shouldn't share cups or utensils with ...

  6. Single Low Dose Primaquine (0.25mg/kg) Does Not Cause Clinically Significant Haemolysis in G6PD Deficient Subjects

    PubMed Central

    Bancone, Germana; Chowwiwat, Nongnud; Somsakchaicharoen, Raweewan; Poodpanya, Lalita; Moo, Paw Khu; Gornsawun, Gornpan; Kajeechiwa, Ladda; Thwin, May Myo; Rakthinthong, Santisuk; Nosten, Suphak; Thinraow, Suradet; Nyo, Slight Naw; Ling, Clare L.; Wiladphaingern, Jacher; Kiricharoen, Naw Lily; Moore, Kerryn A.; White, Nicholas J.; Nosten, Francois

    2016-01-01

    Background Primaquine is the only drug consistently effective against mature gametocytes of Plasmodium falciparum. The transmission blocking dose of primaquine previously recommended was 0.75mg/kg (adult dose 45mg) but its deployment was limited because of concerns over haemolytic effects in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD deficiency is an inherited X-linked enzymatic defect that affects an estimated 400 million people around the world with high frequencies (15–20%) in populations living in malarious areas. To reduce transmission in low transmission settings and facilitate elimination of P. falciparum, the World Health Organization now recommends adding a single dose of 0.25mg/kg (adult dose 15mg) to Artemisinin-based Combination Therapies (ACTs) without G6PD testing. Direct evidence of the safety of this low dose is lacking. Adverse events and haemoglobin variations after this treatment were assessed in both G6PD normal and deficient subjects in the context of targeted malaria elimination in a malaria endemic area on the North-Western Myanmar-Thailand border where prevalence of G6PD deficiency (Mahidol variant) approximates 15%. Methods and Findings The tolerability and safety of primaquine (single dose 0.25 mg base/kg) combined with dihydroartemisinin-piperaquine (DHA-PPQ) given three times at monthly intervals was assessed in 819 subjects. Haemoglobin concentrations were estimated over the six months preceding the ACT + primaquine rounds of mass drug administration. G6PD deficiency was assessed with a phenotypic test and genotyping was performed in male subjects with deficient phenotypes and in all females. Fractional haemoglobin changes in relation to G6PD phenotype and genotype and primaquine round were assessed using linear mixed-effects models. No adverse events related to primaquine were reported during the trial. Mean fractional haemoglobin changes after each primaquine treatment in G6PD deficient subjects (-5

  7. Robotic Stereotactic Radioablation Concomitant With Neo-Adjuvant Chemotherapy for Breast Tumors

    SciTech Connect

    Bondiau, Pierre-Yves; Bahadoran, Phillipe; Lallement, Michel; Birtwisle-Peyrottes, Isabelle; Chapellier, Claire; Chamorey, Emmanuel; Courdi, Adel; Quielle-Roussel, Catherine; Thariat, Juliette; Ferrero, Jean-Marc

    2009-11-15

    Purpose: Robotic stereotactic radioablation (RSR) allows stereotactic irradiation of thoracic tumors; however, it has never been used for breast tumors and may have a real potential. We conducted a Phase I study, including neoadjuvant chemotherapy (NACT), a two-level dose-escalation study (6.5 Gy x 3 fractions and 7.5 Gy x 3 fractions) using RSR and breast-conserving surgery followed by conventional radiotherapy. Materials and Methods: To define toxicity, we performed a dermatologic exam (DE) including clinical examination by two independent observers and technical examination by colorimetry, dermoscopy, and skin ultrasound. DE was performed before NACT (DE0), at 36 days (DE1), at 56 days (DE2), after the NACT treatment onset, and before surgery (DE3). Surgery was performed 4-8 weeks after the last chemotherapy session. A pathologic examination was also performed. Results: There were two clinical complete responses and four clinical partial responses at D56 and D85. Maximum tolerable dose was not reached. All patients tolerated RSR with no fatigue; 2 patients presented with mild pain after the third fraction of the treatment. There was no significant toxicity measured with ultrasound and dermoscopy tests. Postoperative irradiation (50 Gy) has been delivered without toxicity. Conclusion: The study showed the feasibility of irradiation with RSR combined with chemotherapy and surgery for breast tumors. There was no skin toxicity at a dose of 19.5 Gy or 22.5 Gy delivered in three fractions combined with chemotherapy. Lack of toxicity suggested that the dose could be increased further. Pathologic response was acceptable.

  8. Toxic optic neuropathy in the setting of docetaxel chemotherapy: a case report

    PubMed Central

    2014-01-01

    Background To describe the first reported case of toxic optic neuropathy secondary to docetaxel (Taxotere®) chemotherapy. Case presentation A 53-year-old female presented with predominantly unilateral visual loss, but extensive bilateral visual field defects and bilateral optic nerve head swelling 2 weeks after first dose of docetaxel (Taxotere®) and trastuzumab (Herceptin®) chemotherapy for a left sided node-positive, HER2 positive breast cancer. Extensive investigation ruled out other causes of optic neuropathy. She was treated with high dose corticosteroids intravenously for 1 week then a tapering oral dose over 8 weeks. Visual field defects gradually resolved and visual acuity improved. Docetaxel chemotherapy was discontinued but targeted therapy with trastuzumab continued without further complication. Conclusion Docetaxel can cause a toxic optic neuropathy possibly due to an ischemic or neurotoxic mechanism at the optic nerve head. With cessation of docetaxel therapy and treatment with systemic corticosteroids, visual recovery can occur without significant residual visual deficit. PMID:24564293

  9. Increased nephrotoxicity of combination taxol and cisplatin chemotherapy in gynecologic cancers as compared to cisplatin alone.

    PubMed

    Merouani, A; Davidson, S A; Schrier, R W

    1997-01-01

    To investigate the increased nephrotoxicity of taxol and cisplatin combination chemotherapy in gynecologic cancers as compared to cisplatin alone, the medical records of 25 patients with gynecological cancers were reviewed for evaluation of nephrotoxicity after chemotherapy treatment. The data included age, serum creatinine, calculated creatinine clearance, initial and cumulative dose of cisplatin and taxol, primary site of the cancer, renal ultrasound and hydration protocols. Renal function was evaluated before, during and 6 months after chemotherapy. Renal dysfunction was defined as a greater than 25% decrease in creatinine clearance. Comparing 11 patients treated with taxol and cisplatin versus 14 treated with cisplatin alone, there was a significant difference in effect on renal function. Nine of 11 patients (81%) treated with the combination chemotherapy had a greater than 25% decrease in creatinine clearance while only 4 of the 14 patients (29%) treated with cisplatin alone had such a decrease in creatinine clearance (p < 0.004). The patients treated with the combination chemotherapy, however, received a higher dose of cisplatin (80.4 vs. 66.4 mg/m2, p < 0.02) and were treated longer (6.7 vs. 4.3 months, p < 0.002). Nevertheless, when the patients were matched for age, initial dose and cumulative dose of cisplatin, a higher frequency of nephrotoxicity persisted in patients treated with taxol and cisplatin as compared to cisplatin alone (72 as compared to 20%, p < 0.02). The patients in both groups were comparably hydrated; prerenal failure and urinary tract obstruction were excluded in all patients. Six months after completion of chemotherapy, a significantly lower creatinine clearance was still observed in patients treated with taxol and cisplatin combination therapy (46 vs. 76 ml/min, p < 0.01). In summary, a retrospective analysis of renal function in patients with gynecological cancers showed an increased nephrotoxicity in patients treated with taxol and

  10. Combination chemotherapy with docetaxel and carboplatin for elderly patients with endometrial cancer

    PubMed Central

    YOSHIDA, HIROYUKI; IMAI, YUICHI; FUJIWARA, KEIICHI

    2016-01-01

    Approximately half of all endometrial cancer cases are diagnosed in patients aged >65 years. The objective of this study was to compare the tolerability and effectiveness of combination chemotherapy with docetaxel and carboplatin between endometrial cancer patients older and younger than 65 years of age. Chemotherapy-naive patients with endometrial cancer were enrolled in this retrospective study between April, 2008 and March, 2015. The patients received docetaxel (60 mg/m2) and carboplatin (area under the curve of 6 mg/ml/min) on day 1 of a 3-week cycle. The tolerability and effectiveness of this regimen were analyzed. A total of 41 patients with endometrial cancer were enrolled in this study, of whom 26 (63%) were aged <65 years and 15 (37%) were aged ≥65 years. There were no significant differences with regard to Eastern Cooperative Oncology Group performance status score and disease stage between the two groups. Patients aged >65 years were significantly more likely to have serous or clear-cell histology and high-grade tumors compared with the younger group (P=0.014 and 0.012, respectively). Although the number of chemotherapy cycles, cycle delays and treatment interruptions were comparable between older and younger patients, there was a trend toward more dose reductions in the older group (P=0.12). The incidence of hematological toxicities did not differ significantly between the two groups. The incidence of grade 3/4 diarrhea was significantly higher in the older group (P=0.014) and hypersensitivity was significantly more frequent in the younger group (P=0.035). Patients aged ≥65 years had equivalent response rates, progression-free survival and overall survival compared with those aged <65 years. These results suggest that combination chemotherapy with docetaxel and carboplatin was tolerable and effective for the treatment of elderly chemotherapy-naive patients with endometrial cancer. PMID:27123279

  11. Glutamine facilitates chemotherapy while reducing toxicity.

    PubMed

    Klimberg, V S; Nwokedi, E; Hutchins, L F; Pappas, A A; Lang, N P; Broadwater, J R; Read, R C; Westbrook, K C

    1992-01-01

    Dose intensification of chemotherapy is thought to increase survival. With recent advances in hemopoietic cell modulators such as granulocyte colony stimulating factor, the limiting toxicity of intensifying chemotherapeutic regimens has become the severity of the associated enterocolitis. In animal models, glutamine protects the host from methotrexate-induced enterocolitis. This study evaluates the effects of a glutamine-supplemented diet on the tumoricidal effectiveness of methotrexate. Sarcoma-bearing Fisher 344 rats (n = 30) were pair-fed an isocaloric elemental diet containing 1% glutamine or an isonitrogenous amount of glycine beginning on day 25 of the study. Rats from each group received two intraperitoneal injections of methotrexate (5 mg/kg) or saline on days 26 and 33 of the study. On day 40, rats were killed, tumor volume and weight were recorded, and tumor glutaminase activity and tumor morphometrics were measured. Blood was taken for arterial glutamine content, complete blood count, and blood culture. The gut was processed for glutaminase activity and synthesis phase of the deoxyribonucleic acid. In rats receiving methotrexate, the tumor volume loss was nearly doubled when glutamine was added to the diet. Significant differences in tumor glutaminase activity and morphometrics were not detected. The toxicity to the host was ameliorated. Significantly increased synthesis phase of deoxyribonucleic acid of the whole jejunum, decreased bacteremia, "sepsis," and mortality were demonstrated. Glutamine supplementation enhances the tumoricidal effectiveness of methotrexate while reducing its morbidity and mortality in this sarcoma rat model. PMID:1287230

  12. Mastectomy following preoperative chemotherapy. Strict operative criteria control operative morbidity.

    PubMed

    Broadwater, J R; Edwards, M J; Kuglen, C; Hortobagyi, G N; Ames, F C; Balch, C M

    1991-02-01

    The surgical morbidity associated with aggressive preoperative chemotherapy in 106 patients with advanced primary breast cancer who had chemotherapy followed by mastectomy was examined. These patients were compared with a group of 91 consecutive patients who had mastectomy without preoperative chemotherapy. Strict operative criteria were used to determine the timing of mastectomy following chemotherapy. Wound infection rates were no different in the preoperative chemotherapy group compared to the mastectomy-alone groups (7% versus 4%; p = 0.62). The incidence of wound necrosis was similar (11% versus 6%; p = 0.29). Seroma formation was decreased significantly in the preoperative chemotherapy group compared to the mastectomy-alone group (15% versus 28%; p = 0.04). Intensive preoperative chemotherapy did not delay the reinstitution of postoperative treatment (30% versus 20%; p = 0.27). However, when delay in instituting postoperative chemotherapy was more than 30 days, there was a significant decrease in overall survival rate (p = 0.04). This study provides evidence that intensive preoperative chemotherapy and mastectomy can be performed without increased morbidity. Furthermore it is important to institute systemic chemotherapy within 30 days of mastectomy to achieve maximum survival. PMID:1992938

  13. Capecitabine metronomic chemotherapy inhibits the proliferation of gastric cancer cells through anti-angiogenesis.

    PubMed

    Yuan, Fei; Shi, Hailong; Ji, Jun; Cai, Qu; Chen, Xuehua; Yu, Yingyan; Liu, Bingya; Zhu, Zhenggang; Zhang, Jun

    2015-04-01

    To evaluate the inhibitory effect and mechanism of capecitabine metronomic chemotherapy on gastric cancer cells. In vitro, the effects of 5-fluorouracil (Fu) metronomic chemotherapy on proliferation, apoptosis, tube formation ability, and angiogenesis were detected. In vivo, Ki-67, CD34 and VEGF were detected by immunohistochemical staining (IHC). Flow cytometry was used to detect the percentage of circulating endothelial progenitors (CEPs), and VEGF and PDGF were detected by ELISA in the peripheral blood of nude mice. The proliferation of the SGC-7901 and AGS gastric cancer cell lines in the metronomic 5-Fu group was decreased compared with the control group in vitro. The total length of the small tubes and tubular junction numbers were significantly lower in the metronomic group than the control group. The VEGF and PDGF levels in the cell culture supernatants were lower in the metronomic group than the control group. Compared with the control group, the CEP percentage was decreased in the peripheral blood of tumor-bearing nude mice following treatment with metronomic 5-Fu or capecitabine chemotherapy. No significant changes were found in the conventional or control group. In the peripheral blood of tumor-bearing nude mice, the VEGF and PDGF levels were decreased in the metronomic groups. Metronomic 5-Fu inhibited the proliferation of gastric cancer cells in vitro and in vivo, and their antitumor effects were non-inferior to those of conventional dose chemotherapy, with mild side effects. Thus, tumor inhibition may be attributed to anti-angiogenesis. PMID:25634241

  14. Relative Contributions of Radiation and Cisplatin-Based Chemotherapy to Sensorineural Hearing Loss in Head-and-Neck Cancer Patients

    SciTech Connect

    Hitchcock, Ying J. Tward, Jonathan D.; Szabo, Aniko; Bentz, Brandon G.; Shrieve, Dennis C.

    2009-03-01

    Purpose: To investigate the risk of sensorineural hearing loss (SNHL) in patients with head-and-neck cancer and treated with radiation therapy (RT) or concomitant cisplatin-based chemoradiation, the relationship among SNHL and radiation dose to the cochlea, the use of two common cisplatin dose regimens. Methods and Materials: A total of 62 head-and-neck cancer patients treated with curative intent were included in this prospective study. Of the patients, 21 received RT alone, 27 received 40 mg/m{sup 2} weekly cisplatin, 13 received 100 mg/m{sup 2} every 3 weeks during RT, and 1 received RT with weekly epidermal growth factor receptor inhibitor antibody. The effect of chemotherapy and RT dose on hearing was determined using a model that accounted for the age and variability between each ear for each patient. Results: We constructed a model to predict dose-dependent hearing loss for RT or cisplatin-based chemotherapy either alone or in combination. For patients only receiving RT, no significant hearing loss was found at doses to the cochlea of less than 40 Gy. Patients receiving 100 mg/m{sup 2} or 40 mg/m{sup 2} of cisplatin chemotherapy had an estimated +21.5 dB and +9.5 dB hearing loss at 8,000 Hz with low radiation doses (10 Gy), which rose to +38.4 dB and +18.9 dB for high radiation doses (40 Gy). Conclusions: Use of RT alone with doses of less than 40 Gy did not result in clinically significant hearing loss. High-frequency SNHL was profoundly damaged in patients who received concomitant cisplatin when doses of 100 mg/m{sup 2} were used. The threshold cochlear dose for hearing loss with cisplatin-based chemotherapy and RT was predicted to be 10 Gy. The inner ear radiation dose constraints and cisplatin dose intensity should be considered in the treatment of advanced head-and-neck cancer.

  15. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Methodology, Drugs and Bidirectional Chemotherapy.

    PubMed

    Valle, S J; Alzahrani, N A; Liauw, W; Sugarbaker, P H; Bhatt, A; Morris, D L

    2016-06-01

    Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) combined have been recognized as standard of care for treatment of a subset of patients with peritoneal carcinomatosis (PC). The aim of CRS is to eliminate all macroscopic disease through a series of visceral resections followed by targeting any residual microscopic disease with intraperitoneal chemotherapy, exposing the peritoneal surfaces to a high concentration of chemotherapy with a lower systemic toxicity. Different regimes of intraperitoneal chemotherapy include HIPEC, early postoperative intraperitoneal chemotherapy (EPIC) and bidirectional chemotherapy. The efficacy and modality of treatment with intraperitoneal chemotherapy is dependent on multiple factors including the chosen cytotoxic agent and its pharmacokinetics and pharmacodynamics. There is no standardized methodology for intraperitoneal chemotherapy administration. This review will discuss the pharmacological principles of the various intraperitoneal chemotherapy techniques. PMID:27065705

  16. Chemotherapy for Stage II Colon Cancer.

    PubMed

    Varghese, Anna

    2015-12-01

    The adjuvant treatment of patients with stage II colon cancer is an area of controversy in medical oncology. Adjuvant chemotherapy aims to eradicate micrometastatic disease present at the time of surgery, preventing the development of distant metastatic disease and thereby curing those patients of their cancer. National and international guidelines for the adjuvant treatment of stage II colon cancer recommend a range of treatment options from observation to chemotherapy with single-agent or combination regimens, depending on the presence or absence of high-risk features (poorly differentiated histology, presence of lymphovascular invasion, presence of perineural invasion, report of < 12 lymph nodes, bowel obstruction, localized perforation, or positive margins). In the one prospective study designed to address the role of adjuvant chemotherapy in stage II colon cancer, a small but statistically significant benefit in overall survival was seen for those patients who received adjuvant chemotherapy; however, multiple meta-analyses and retrospective subgroup analyses have called these findings into question. Though there may be a role for adjuvant chemotherapy in the treatment of patients with stage II colon cancer, its incremental benefit is small, at best, and comes with the risks of real and rarely fatal complications of chemotherapy. PMID:26648796

  17. Photon buildup factors of some chemotherapy drugs.

    PubMed

    Kavaz, Esra; Ahmadishadbad, Nader; Özdemir, Yüksel

    2015-02-01

    Everyday more and more people are diagnosed with some form of cancer. Some are treatable with chemotherapy alone, while others need radiotherapy and occasionally surgery. Recently, concurrent administration of chemotherapy and radiotherapy has been increasingly used in cancer treatment, leading to improvements in survival as well as quality of life. Accordingly, interaction of chemotherapy drugs with radiation will be meaningful to examine. In the present study, gamma ray energy absorption and exposure of buildup factors were computed using the five-parameter geometric progression (G-P) fitting formula for some chemotherapy drugs in the energy range 0.015-15 MeV, and for penetration depths up to 40 mean free path (mfp). The generated energy absorption (EABF) and exposure buildup factors (EBF) of chemotherapy drugs have been studied as a function of penetration depth and incident photon energy. The significant variations in EABF and EBF for chemotherapy drugs have been observed at the moderate energy region. It has been concluded that the buildup of photons is less in azathioprine and is more in vinblastine compared with other drugs. Buildup factors investigated in the present work could be useful in radiation dosimetry and therapy. PMID:25661335

  18. Acute Esophagus Toxicity in Lung Cancer Patients After Intensity Modulated Radiation Therapy and Concurrent Chemotherapy

    SciTech Connect

    Kwint, Margriet; Uyterlinde, Wilma; Nijkamp, Jasper; Chen, Chun; Bois, Josien de; Sonke, Jan-Jakob; Heuvel, Michel van den; Knegjens, Joost; Herk, Marcel van; Belderbos, Jose

    2012-10-01

    Purpose: The purpose of this study was to investigate the dose-effect relation between acute esophageal toxicity (AET) and the dose-volume parameters of the esophagus after intensity modulated radiation therapy (IMRT) and concurrent chemotherapy for patients with non-small cell lung cancer (NSCLC). Patients and Methods: One hundred thirty-nine patients with inoperable NSCLC treated with IMRT and concurrent chemotherapy were prospectively analyzed. The fractionation scheme was 66 Gy in 24 fractions. All patients received concurrently a daily dose of cisplatin (6 mg/m Superscript-Two ). Maximum AET was scored according to Common Toxicity Criteria 3.0. Dose-volume parameters V5 to V70, D{sub mean} and D{sub max} of the esophagus were calculated. A logistic regression analysis was performed to analyze the dose-effect relation between these parameters and grade {>=}2 and grade {>=}3 AET. The outcome was compared with the clinically used esophagus V35 prediction model for grade {>=}2 after radical 3-dimensional conformal radiation therapy (3DCRT) treatment. Results: In our patient group, 9% did not experience AET, and 31% experienced grade 1 AET, 38% grade 2 AET, and 22% grade 3 AET. The incidence of grade 2 and grade 3 AET was not different from that in patients treated with CCRT using 3DCRT. The V50 turned out to be the most significant dosimetric predictor for grade {>=}3 AET (P=.012). The derived V50 model was shown to predict grade {>=}2 AET significantly better than the clinical V35 model (P<.001). Conclusions: For NSCLC patients treated with IMRT and concurrent chemotherapy, the V50 was identified as most accurate predictor of grade {>=}3 AET. There was no difference in the incidence of grade {>=}2 AET between 3DCRT and IMRT in patients treated with concurrent chemoradiation therapy.

  19. Modification of chemotherapy by nitroimidazoles

    SciTech Connect

    Siemann, D.W.

    1984-09-01

    The potentiation of chemotherapeutic agents by radiation sensitizers has been extensively studied for several years. There is little doubt that the effectiveness of certain anti-cancer drugs, primarily alkylating agents, can readily be enhanced both in vitro and in vivo through the addition of a sensitizer. While enhanced effects have been observed in certain critical normal tissues, in general most animal model studies have demonstrated a therapeutic gain at large sensitizer doses. This approach to combination therapies therefore appears promising. Yet many questions concerning the interaction between chemotherapeutic agents and radiosensitizers, particularly in the aspects of modification of chemotherapy by nitroimidazoles are reviewed and discussed. These address the importance in chemopotentiation of (i) hypoxia, (ii) alterations in DNA damage and/or repair, (iii) depletion of intracellular sulfhydryls and (iv) modification of drug pharmacokinetics.

  20. Effects of the polysaccharides extracted from Ganoderma lucidum on chemotherapy-related fatigue in mice.

    PubMed

    Ouyang, Ming-Zi; Lin, Li-Zhu; Lv, Wen-Jiao; Zuo, Qian; Lv, Zhuo; Guan, Jie-Shan; Wang, Shu-Tang; Sun, Ling-Ling; Chen, Han-Rui; Xiao, Zhi-Wei

    2016-10-01

    The weight-loaded swimming capability, tumor growth, survival time and biochemical markers of Ganoderma lucidum polysaccharides (GLPs) in a chemotherapy-related fatigue mouse model were tested in the present study. The results showed that the middle-dose GLPs (GLP-M) and the high-dose GLPs (GLP-H) could increase the exhausting swimming time, which was observed to decrease in the cisplatin control group(PCG) and the tumor control group (TCG).The GLP-M and the GLP-H had reduced serum levels of tumor necrosis factor-αand interleukin-6, which were up-regulated by cisplatin. Cisplatin and the presence of tumor significantly enhanced the malondialdehyde (MDA) content and inhibited the activity of superoxide dismutase (SOD) in the muscle. Administration of GLPs at a high dose decreased the levels of MDA and up-regulated the SOD activity. The high-dose GLPs+cisplatin group presented a decreased tendency of tumor volume and a lower tumor weight compared with PCG. Moreover, the mice in the GLP-M and GLP-H groups had longer survival times compared with the mice in the TCG and PCG.The levels of creatinine and serum blood urea nitrogen, which are up-regulated by cisplatin, were significantly reduced by GLP-M and GLP-H. Therefore, these results suggest that GLPs might improve chemotherapy-related fatigue via regulation of inflammatory responses, oxidative stress and reduction of nephrotoxicity. PMID:27208798

  1. Peripheral neuropathy induced by combination chemotherapy of docetaxel and cisplatin.

    PubMed Central

    Hilkens, P. H.; Pronk, L. C.; Verweij, J.; Vecht, C. J.; van Putten, W. L.; van den Bent, M. J.

    1997-01-01

    Docetaxel, a new semisynthetic taxoid that has demonstrated promising activity as an antineoplastic agent, was administered in combination with cisplatin to 63 patients in a dose-escalating study. As both drugs were known to be potentially neurotoxic, peripheral neurotoxicity was prospectively assessed in detail. Neuropathy was evaluated by clinical sum-score for signs and symptoms and by measurement of the vibration perception threshold (VPT). The severity of neuropathy was graded according to the National Cancer Institute's 'Common Toxicity Criteria'. The docetaxel-cisplatin combination chemotherapy induced a predominantly sensory neuropathy in 29 (53%) out of 55 evaluable patients. At cumulative doses of both cisplatin and docetaxel above 200 mg m(-2), 26 (74%) out of 35 patients developed a neuropathy which was mild in 15, moderate in ten and severe in one patient. Significant correlations were present between both the cumulative dose of docetaxel and cisplatin and the post-treatment sum-score of neuropathy (P < 0.01) as well as the post-treatment VPT (P < 0.01). The neurotoxic effects of this combination were more severe than either cisplatin or docetaxel as single agent at similar doses. PMID:9020489

  2. Mitoxantrone-loaded albumin microspheres for localized intratumoral chemotherapy of breast cancer

    NASA Astrophysics Data System (ADS)

    Almond, Brett Anthony

    The safety and efficacy of conventional chemotherapy is limited by its toxicity. The direct intratumoral injection of free or microsphere-loaded antineoplastic drugs is a promising modality for the treatment of solid tumors. Intratumoral chemotherapy delivers high localized doses of cytotoxic drugs to the tumor tissues than does systemic (intravenous) chemotherapy and it decreases systemic drug concentrations and toxicities. The use of drug-loaded microspheres also provides a prolonged release of drug into the surrounding tumor tissues, increasing exposure of the neoplasm to therapeutic levels of the cytotoxic drug. Mitoxantrone and 5-fluorouracil-loaded albumin microspheres were synthesized. The microspheres were synthesized using a suspension crosslinking technique and a glutardehyde crosslinking agent. The particle-size distribution of the microspheres was controlled by adjusting the emulsion energy and the concentration of cellulose acetate butyrate, the emulsion stabilization agent. Both microsphere size and crosslink density (glutaraldehyde concentration) were found to affect the in vitro release of loaded drugs in in vitro infinite sink conditions. The in vivo efficacy and toxicity of intratumoral chemotherapy with free and microsphere-loaded mitoxantrone were evaluated in a 16/C murine mammary adenocarcinoma model. Intratumoral chemotherapy with free mitoxantrone significantly improved survival and decreased toxicity compared to intravenously delivered drug. The efficacy of two size distributions of mitoxantrone-loaded albumin microspheres, corresponding to mean diameters of 5 to 10 mum and 20 to 40 mum, were evaluated delivered both alone and in combination with free mitoxantrone. Intratumoral injection of mitoxantrone-loaded microspheres was found to allow the safe delivery of increased doses compared to free drug. The maximum tolerated doses were approximately 40 mg/kg compared to 12 mg/kg, respectively. Intratumoral chemotherapy using free and

  3. Glutamate carboxypeptidase inhibition reduces the severity of chemotherapy-induced peripheral neurotoxicity in rat.

    PubMed

    Carozzi, Valentina A; Chiorazzi, Alessia; Canta, Annalisa; Lapidus, Rena G; Slusher, Barbara S; Wozniak, Krystyna M; Cavaletti, Guido

    2010-05-01

    Chemotherapy is the most common method to treat cancer. The use of certain antineoplastic drugs, however, is associated with the development of peripheral neuropathy that can be dose-limiting. Excitotoxic glutamate release, leading to excessive glutamatergic neurotransmission and activation of N-methyl-D-aspartate (NMDA) receptors, is associated with neuronal damage and death in several nervous system disorders. N-Acetyl-aspartyl-glutamate (NAAG) is an abundant neuropeptide widely distributed in the central and peripheral nervous system which is physiologically hydrolyzed by the enzyme glutamate carboxypeptidase into N-Acetyl-aspartyl (NAA) and glutamate. Pharmacological inhibition of glutamate carboxypeptidase results in decreased glutamate and increased endogenous NAAG and has been shown to provide neuroprotection in several preclinical models. Here, we report the neuroprotective effect of an orally available glutamate carboxypeptidase inhibitor on three well-established animal models of chemotherapy (cisplatin, paclitaxel, bortezomib)-induced peripheral neuropathy. In all cases, glutamate carboxypeptidase inhibition significantly improved the chemotherapy-induced nerve conduction velocity deficits. In addition, morphological and morphometrical alterations induced by cisplatin and bortezomib in dorsal root ganglia (DRG) were improved by glutamate carboxypeptidase inhibition. Our data support a novel approach for the treatment of chemotherapy-induced peripheral neuropathy. PMID:19763734

  4. Human circulating plasma DNA significantly decreases while lymphocyte DNA damage increases under chronic occupational exposure to low-dose gamma-neutron and tritium β-radiation.

    PubMed

    Korzeneva, Inna B; Kostuyk, Svetlana V; Ershova, Liza S; Osipov, Andrian N; Zhuravleva, Veronika F; Pankratova, Galina V; Porokhovnik, Lev N; Veiko, Natalia N

    2015-09-01

    The blood plasma of healthy people contains cell-fee (circulating) DNA (cfDNA). Apoptotic cells are the main source of the cfDNA. The cfDNA concentration increases in case of the organism's cell death rate increase, for example in case of exposure to high-dose ionizing radiation (IR). The objects of the present research are the blood plasma and blood lymphocytes of people, who contacted occupationally with the sources of external gamma/neutron radiation or internal β-radiation of tritium N = 176). As the controls (references), blood samples of people, who had never been occupationally subjected to the IR sources, were used (N = 109). With respect to the plasma samples of each donor there were defined: the cfDNA concentration (the cfDNA index), DNase1 activity (the DNase1 index) and titre of antibodies to DNA (the Ab DNA index). The general DNA damage in the cells was defined (using the Comet assay, the tail moment (TM) index). A chronic effect of the low-dose ionizing radiation on a human being is accompanied by the enhancement of the DNA damage in lymphocytes along with a considerable cfDNA content reduction, while the DNase1 content and concentration of antibodies to DNA (Ab DNA) increase. All the aforementioned changes were also observed in people, who had not worked with the IR sources for more than a year. The ratio cfDNA/(DNase1×Ab DNA × TM) is proposed to be used as a marker of the chronic exposure of a person to the external low-dose IR. It was formulated the assumption that the joint analysis of the cfDNA, DNase1, Ab DNA and TM values may provide the information about the human organism's cell resistivity to chronic exposure to the low-dose IR and about the development of the adaptive response in the organism that is aimed, firstly, at the effective cfDNA elimination from the blood circulation, and, secondly - at survival of the cells, including the cells with the damaged DNA. PMID:26113293

  5. SU-E-J-66: Significant Anatomical and Dosimetric Changes Observed with the Pharyngeal Constrictor During Head and Neck Radiotherapy Elicited From Daily Deformable Image Registration and Dose Accumulation

    SciTech Connect

    Kumarasiri, A; Siddiqui, F; Liu, C; Kamal, M; Fraser, C; Chetty, I; Kim, J

    2015-06-15

    Purpose: To evaluate the anatomical changes and associated dosimetric consequences to the pharyngeal constrictor (PC) that occurs during head and neck radiotherapy (H&N RT). Methods: A cohort of 13 oro-pharyngeal cancer patients, who had daily CBCT’s for localization, was retrospectively studied. On every 5th CBCT, PC was manually delineated by a radiation oncologist. The anterior-posterior PC thickness was measured at the C3 level. Delivered dose to PC was estimated by calculating daily doses on CBCT’s, and accumulating to corresponding planning CT images. For accumulation, a parameter-optimized B- spline-based deformable image registration algorithm (Elastix) was used, in conjunction with an energy-mass mapping dose transfer algorithm. Mean and maximum dose (Dmean, Dmax) to PC was determined and compared with corresponding planned quantities. Results: The mean (±standard deviation) volume increase (ΔV) and thickness increase (Δt) over the course of 35 total fractions were 54±33% (11.9±7.6 cc), and 63±39% (2.9±1.9 mm), respectively. The resultant cumulative mean dose increase from planned dose to PC (ΔDmean) was 1.4±1.3% (0.9±0.8 Gy), while the maximum dose increase (ΔDmax) was 0.0±1.6% (0.0±1.1 Gy). Patients with adaptive replanning (n=6) showed a smaller mean dose increase than those without (n=7); 0.5±0.2% (0.3±0.1 Gy) vs. 2.2±1.4% (1.4±0.9 Gy). There was a statistically significant (p<0.0001) strong correlation between ΔDmean and Δt (Pearson coefficient r=0.78), and a moderate-to-strong correlation (r=0.52) between ΔDmean and ΔV. Correlation between ΔDmean and weight loss ΔW (r=0.1), as well as ΔV and ΔW (r=0.2) were negligible. Conclusion: Patients were found to undergo considerable anatomical changes to pharyngeal constrictor during H&N RT, resulting in non-negligible dose deviations from intended dose. Results are indicative that pharyngeal constrictor thickness, measured at C3 level, is a good predictor for the dose change to

  6. Managing Chemotherapy Side Effects: Infection

    MedlinePlus

    ... ational C ancer I nstitute Managing Chemotherapy Side Effects Infection “I am extra careful to stay away ... doctor or nurse right away. Managing Chemotherapy Side Effects: Infection Take these steps to lower your chances ...

  7. Managing Chemotherapy Side Effects: Diarrhea

    MedlinePlus

    ... ational C ancer I nstitute Managing Chemotherapy Side Effects U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES National ... before taking medicine for diarrhea. Managing Chemotherapy Side Effects: Diarrhea These foods and drinks may help if ...

  8. CXCR4 Protein Epitope Mimetic Antagonist POL5551 Disrupts Metastasis and Enhances Chemotherapy Effect in Triple-Negative Breast Cancer.

    PubMed

    Xiang, Jingyu; Hurchla, Michelle A; Fontana, Francesca; Su, Xinming; Amend, Sarah R; Esser, Alison K; Douglas, Garry J; Mudalagiriyappa, Chidananda; Luker, Kathryn E; Pluard, Timothy; Ademuyiwa, Foluso O; Romagnoli, Barbara; Tuffin, Gérald; Chevalier, Eric; Luker, Gary D; Bauer, Michael; Zimmermann, Johann; Aft, Rebecca L; Dembowsky, Klaus; Weilbaecher, Katherine N

    2015-11-01

    The SDF-1 receptor CXCR4 has been associated with early metastasis and poorer prognosis in breast cancers, especially the most aggressive triple-negative subtype. In line with previous reports, we found that tumoral CXCR4 expression in patients with locally advanced breast cancer was associated with increased metastases and rapid tumor progression. Moreover, high CXCR4 expression identified a group of bone marrow-disseminated tumor cells (DTC)-negative patients at high risk for metastasis and death. The protein epitope mimetic (PEM) POL5551, a novel CXCR4 antagonist, inhibited binding of SDF-1 to CXCR4, had no direct effects on tumor cell viability, but reduced migration of breast cancer cells in vitro. In two orthotopic models of triple-negative breast cancer, POL5551 had little inhibitory effect on primary tumor growth, but significantly reduced distant metastasis. When combined with eribulin, a chemotherapeutic microtubule inhibitor, POL5551 additively reduced metastasis and prolonged survival in mice after resection of the primary tumor compared with single-agent eribulin. Hypothesizing that POL5551 may mobilize tumor cells from their microenvironment and sensitize them to chemotherapy, we used a "chemotherapy framing" dosing strategy. When administered shortly before and after eribulin treatment, three doses of POL5551 with eribulin reduced bone and liver tumor burden more effectively than chemotherapy alone. These data suggest that sequenced administration of CXCR4 antagonists with cytotoxic chemotherapy synergize to reduce distant metastases. PMID:26269605

  9. Low acute hematological toxicity during chemotherapy predicts reduced disease control in advanced Hodgkin's disease.

    PubMed

    Brosteanu, O; Hasenclever, D; Loeffler, M; Diehl, V

    2004-03-01

    Chemotherapy-treated patients with advanced Hodgkin's disease (HD) differ considerably in acute hematotoxicity. Hematotoxicity may be indicative of pharmacological and metabolic heterogeneity. We hypothesized that low hematotoxicity might correlate with reduced systemic dose and thus reduced disease control. A total of 266 patients with advanced HD treated with cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine, and dacarbazine (COPP-ABVD) were analyzed (HD6 trial of the German Hodgkin's Lymphoma Study Group). The reported WHO grade of leukocytopenia was averaged over chemotherapy cycles given and weighted with the reciprocal dose intensity of the corresponding cycle. The low and high toxicity groups were defined in retrospect as having had an averaged WHO grade of leukocytopenia 2.1, respectively. The independent impact of low hematological toxicity on freedom from treatment failure (FFTF) was assessed multivariately adjusting for the international prognostic score for advanced HD. The results were validated in two independent cohorts [181 patients treated with COPP-ABVD (HD9-trial) and 250 patients treated with COPP-ABV-ifosfamide, methotrexate, etoposide, and prednisone (IMEP) (HD6 trial)]. The 5-year FFTF rates were 68% for patients with high toxicity vs 47% for patients with low toxicity [multivariate relative risk (RR) 2.0, 95% confidence interval (CI) 1.4-3.0, p=0.0002]. Patients with low toxicity received significantly higher nominal dose ( p=0.02) and dose intensity ( p<0.0001). This finding was confirmed in both validation cohorts (multivariate RR 2.1, 95% CI 1.2-3.8, p=0.01 and RR 1.5, 95% CI 1.01-2.26, p=0.04, respectively). Patients with low hematotoxicity have significantly higher failure rates despite higher doses and dose intensity. Hematotoxicity is an independent prognostic factor for treatment outcome. This observation suggests a strategy of individualized dosing adapted to hematotoxicity

  10. Chemotherapy, cognitive impairment and hippocampal toxicity.

    PubMed

    Dietrich, J; Prust, M; Kaiser, J

    2015-11-19

    Cancer therapies can be associated with significant central nervous system (CNS) toxicity. While radiation-induced brain damage has been long recognized both in pediatric and adult cancer patients, CNS toxicity from chemotherapy has only recently been acknowledged. Clinical studies suggest that the most frequent neurotoxic adverse effects associated with chemotherapy include memory and learning deficits, alterations of attention, concentration, processing speed and executive function. Preclinical studies have started to shed light on how chemotherapy targets the CNS both on cellular and molecular levels to disrupt neural function and brain plasticity. Potential mechanisms include direct cellular toxicity, alterations in cellular metabolism, oxidative stress, and induction of pro-inflammatory processes with subsequent disruption of normal cellular and neurological function. Damage to neural progenitor cell populations within germinal zones of the adult CNS has been identified as one of the key mechanisms by which chemotherapy might exert long-lasting and progressive neurotoxic effects. Based on the important role of the hippocampus for maintenance of brain plasticity throughout life, several experimental studies have focused on the study of chemotherapy effects on hippocampal neurogenesis and associated learning and memory. An increasing body of literature from both animal studies and neuroimaging studies in cancer patients suggests a possible relationship between chemotherapy induced hippocampal damage and the spectrum of neurocognitive deficits and mood alterations observed in cancer patients. This review aims to briefly summarize current preclinical and neuroimaging studies that are providing a potential link between the neurotoxic effects of chemotherapy and hippocampal dysfunction, highlighting challenges and future directions in this field of investigation. PMID:26086545

  11. Development of regional chemotherapies: feasibility, safety and efficacy in clinical use and preclinical studies

    PubMed Central

    Cai, Shuang; Bagby, Taryn R; Forrest, M Laird

    2011-01-01

    Conventional oral and intravenous chemotherapies permeate throughout the body, exposing healthy tissues to similar cytotoxic drug levels as tumors. This leads to significant dose-limiting toxicities that may prevent patients from receiving sufficient treatment to overcome cancers. Therefore, a number of locoregional drug-delivery strategies have been evaluated and implemented in preclinical studies, clinical trials and in practice, in the past decades to minimize systemic toxicities from chemotherapeutic agents and to improve treatment outcomes. Localized treatment is beneficial because many cancers, such as melanoma, peritoneal cancer and breast cancer, advance locally adjacent to the site of the primary tumors prior to their circulatory invasion. In this article, we will review the feasibility, safety and efficacy of multiple localized chemotherapies in clinical use and preclinical development. PMID:22229080

  12. Intraperitoneal chemotherapy of ovarian cancer by hydrogel depot of paclitaxel nanocrystals.

    PubMed

    Sun, Bo; Taha, Maie S; Ramsey, Benjamin; Torregrosa-Allen, Sandra; Elzey, Bennett D; Yeo, Yoon

    2016-08-10

    Intraperitoneal (IP) chemotherapy is a promising post-surgical therapy of ovarian cancer, but the full potential is yet to be realized. To facilitate IP chemotherapy of ovarian cancer, we developed an in-situ crosslinkable hydrogel depot containing paclitaxel (PTX) nanocrystals (PNC). PNC suppressed SKOV3 cell proliferation more efficiently than microparticulate PTX precipitates (PPT), and the gel containing PNC (PNC-gel) showed a lower maximum tolerated dose than PPT-containing gel (PPT-gel) in mice, indicating greater dissolution and cellular uptake of PNC than PPT. A single IP administration of PNC-gel extended the survival of tumor-bearing mice significantly better than Taxol, but PPT-gel did not. These results support the advantage of PNC over PPT and demonstrate the promise of a gel depot as an IP drug delivery system. PMID:27238443

  13. Modeling Combined Chemotherapy and Particle Therapy for Locally Advanced Pancreatic Cancer

    PubMed Central

    Durante, Marco; Tommasino, Francesco; Yamada, Shigeru

    2015-01-01

    Pancreatic ductal adenocarcinoma is the only cancer for which deaths are predicted to increase in 2014 and beyond. Combined radiochemotherapy protocols using gemcitabine and hypofractionated X-rays are ongoing in several clinical trials. Recent results indicate that charged particle therapy substantially increases local control of resectable and unresectable pancreas cancer, as predicted from previous radiobiology studies considering the high tumor hypoxia. Combination with chemotherapy improves the overall survival (OS). We compared published data on X-ray and charged particle clinical results with or without adjuvant chemotherapy calculating the biological effective dose. We show that chemoradiotherapy with protons or carbon ions results in 1 year OS significantly higher than those obtained with other treatment schedules. Further hypofractionation using charged particles may result in improved local control and survival. A comparative clinical trial using the standard X-ray scheme vs. the best current standard with carbon ions is crucial and may open new opportunities for this deadly disease. PMID:26217585

  14. Antitumor activity of photodynamic therapy, adoptive immunotherapy, and chemotherapy in experimental tumor

    NASA Astrophysics Data System (ADS)

    Canti, Gianfranco L.; Calastretti, Angela; Cubeddu, Rinaldo; Taroni, Paola; Valentini, Gianluca; Reddi, Elena; Palumbo, Giuseppe

    2004-07-01

    Since Photodynamic therapy(PDT) is able to increase the antitumor immunity, in our laboratory we examine the antitumor effect of combination of PDT,with photoactivated Aluminium disulfonated Phthalocianine(ALS2Pc),adoptive immunotherapy, with immune lymphocytes, and chemotherapy on aggressive murine tumor. Mice bearing L1210 tumor were treated at day +4 with PDT ( 5mg/Kg of AlS2Pc and 100mW/cm2 x 10" of exposure of laser light 24hrs. later),at day +6 with Adriamycin(ADR 2mg/Kg) and at day + 7 with immune lymphocytes(IL),collected from L1210 bearing mice pretreated with PDT(2x107 cells).The results show that the combination ADR + PDT + IL demonstrates a significant synergistic antitumor effect while the chemotherapy treatment with low dose of the drug and the adotive immunotherapy treatment are slightly effective. The same positive results were obtained with the combination of PDT,Cisplatin(CDDP 2mg/Kg) and IL,while the CDDP treatment alone and the Il treatment alone are slightly effective. In conclusion these results suggest that it is possible to completely cure animals bearing advanced tumors, with a combined therapy, PDT + adoptive immunotherapy + low dose chemotherapy.

  15. AML cells are differentially sensitive to chemotherapy treatment in a human xenograft model.

    PubMed

    Wunderlich, Mark; Mizukawa, Benjamin; Chou, Fu-Sheng; Sexton, Christina; Shrestha, Mahesh; Saunthararajah, Yogen; Mulloy, James C

    2013-03-21

    As acute myeloid leukemia (AML) xenograft models improve, the potential for using them to evaluate novel therapeutic strategies becomes more appealing. Currently, there is little information on using standard chemotherapy regimens in AML xenografts. Here we have characterized the immunodeficient mouse response to combined Ara-C (cytarabine) and doxorubicin treatment. We observed significant toxicity associated with doxorubicin that required optimization of the route of injection as well as the maximum-tolerated dose for immunodeficient strains. Mice treated with an optimized 5-day induction protocol showed transient weight loss, short-term reduction of peripheral blood cell and platelet counts, and slight anemia. Considerable cytotoxicity was observed in the bone marrow (BM), with primitive LSK cells having a significant survival advantage relative to more mature cells, consistent with the idea of chemotherapy targeting actively growing cells. Treated leukemic mice demonstrated reduced disease burden and increased survival, demonstrating efficacy. AML cells showed significantly increased sensitivity to doxorubicin-containing therapy compared with murine BM cells. Although early treatment could result in some cures, mice with significant leukemia grafts were not cured by using induction therapy alone. Overall, the data show that this model system is useful for the evaluation of novel chemotherapies in combination with standard induction therapy. PMID:23349390

  16. Impact of Polymorphic Variations of Gemcitabine Metabolism, DNA Damage Repair, and Drug-Resistance Genes on the Effect of High-Dose Chemotherapy for Relapsed or Refractory Lymphoid Malignancies.

    PubMed

    Shinozuka, Keiji; Tang, Hongwei; Jones, Roy B; Li, Donghui; Nieto, Yago

    2016-05-01

    The goal of this study was to determine whether single nucleotide polymorphisms (SNPs) in genes involved in gemcitabine metabolism, DNA damage repair, multidrug resistance, and alkylator detoxification influence the clinical outcome of patients with refractory/relapsed lymphoid malignancies receiving high-dose gemcitabine/busulfan/melphalan (Gem/Bu/Mel) with autologous stem cell support. We evaluated 21 germline SNPs of the gemcitabine metabolism genes CDA, deoxycytidine kinase, and hCNT3; DNA damage repair genes RECQL, X-ray repair complementing 1, RAD54L, ATM, ATR, MLH1, MSH2, MSH3, TREX1, EXO1, and TP73; and multidrug-resistance genes MRP2 and MRP5; as well as glutathione-S-transferase GSTP1 in 153 patients with relapsed or refractory lymphoma or myeloma receiving Gem/Bu/Mel. We studied the association of genotypes with overall survival (OS), progression-free survival (PFS), and nonhematological grade 3 or 4 toxicity. CDA C111T and TREX1 Ex14-460C>T genotypes had a significant effect on OS (P = .007 and P = .005, respectively), and CDA C111T, ATR C340T, and EXO1 P757L genotypes were significant predictors for severe toxicity (P = .037, P = .024, and P = .025, respectively) in multivariable models that adjusted for clinical variables. The multi-SNP risk score analysis identified the combined genotypes of TREX1 Ex14-460 TT and hCNT3 Ex5 +25A>G AA as significant predictors for OS and the combination of MRP2 Ex10 + 40GG/GA and MLH1 IVS12-169 TT as significant predictor for PFS. Polymorphic variants of certain genes involved in gemcitabine metabolism and DNA damage repair pathways may be potential biomarkers for clinical outcome in patients with refractory/relapsed lymphoid tumors receiving Gem/Bu/Mel. PMID:26743341

  17. Clinical and histopathological evaluation of the effect of addition of immunotherapy with Mw vaccine to standard chemotherapy in borderline leprosy.

    PubMed

    Kamal, R; Natrajan, M; Katoch, K; Arora, M

    2012-01-01

    This study reports detailed analysis of clinical parameters and clearance of granuloma in borderline leprosy patients treated with immunotherapy and chemotherapy. It aims to assess the additive effect of immunotherapy (Mwvaccine) with standard MDT on clinical status of untreated borderline leprosy cases and on granuloma fraction of untreated borderline leprosy cases. Patients attending the OPD were serially recruited in two groups. A total of 150 cases in one treatment (trial) group (Mw vaccine plus MDT) and 120 cases in another treatment (control) group (MDT only) of border line leprosy have been included. After the formal written consent, detailed clinical examination, charting, smear examination of all untreated borderline patients of both groups was done, biopsies were taken from the active lesions of all patients of both groups at start of therapy and every six month thereafter till the completion of therapy. The same procedure was repeated every six months during the follow-up period. Standard MDT was given to all the patients of both groups according to type of disease. Mw vaccine 0.1 ml (0.5 x 10(9) bacilli) was injected intra-dermally at the start of therapy and every six months in addition to chemotherapy to the treatment group. The BT cases were followed up after 6 doses of MDT and 2 doses of Mw vaccine, and, the BB, BL cases were followed up after 24 doses of MDT plus 5 doses of Mw vaccine. Clinically, greater and faster improvement was observed in all the clinical parameters, faster attainment of smear negativity and two episodes of lepra reaction occurred in cases treated with combined chemotherapy and immunotherapy, as compared to controls (chemotherapy alone) wherein clinical improvement was slower in all parameters, slower attainment of smear negativity in bacillary index and seven showed the occurrence of reactions, histipathologically in addition to more rapid clearance of granuloma in immunotherapy treated group, a significant finding was an

  18. Dorsal column myelopathy following intrathecal chemotherapy for acute lymphoblastic leukemia

    PubMed Central

    Joseph, Prathap Jacob; Reyes, Maria Regina

    2014-01-01

    Objective/context To describe a distinctive clinical and radiographic pattern of myelopathy following intrathecal chemotherapy. Myelopathy is a rare complication of intrathecal chemotherapy used in the treatment of acute lymphoblastic leukemia (ALL). We present a 42-year-old female with T-cell ALL who developed a myelopathy primarily involving the dorsal columns. Method Case report and literature review. Findings Within 24 hours of an injection of intrathecal methotrexate, cytarabine, and hydrocortisone, the patient developed ascending lower limb numbness and balance difficulties progressing to the inability to ambulate. Clinical examination showed profound loss of lower limb proprioception and light touch sensation below T5, mild proximal limb weakness, but preserved pinprick and temperature sensation with intact bowel and bladder function. Initial thoracic and lumbar spine magnetic resonance imaging (MRI) at 1 week revealed no abnormalities. However, repeat imaging at 6 weeks showed abnormal signal in the posterior cord with sparing of the anterior and lateral columns, diffusely involving the lower cervical cord through the conus medullaris. Dermatomal somatosensory-evoked potential (DSEP) conduction abnormalities were consistent with thoracic myelopathy. An empiric trial of high-dose intravenous corticosteroids during inpatient rehabilitation more than 6 weeks later produced no significant clinical improvement. Conclusion/clinical relevance Preferential and persistent dorsal column myelopathy is a distinctive clinical and radiographic presentation of a rare complication of intrathecal chemotherapy. The MRI abnormalities were initially absent, but evolved to consist of multi-level spinal cord T2 and STIR hyperintensity with regional gadolinium enhancement. DSEPs more accurately reflected the clinical level of spinal cord dysfunction. PMID:24090227

  19. Magnetic nanoparticle hyperthermia as an adjuvant cancer therapy with chemotherapy

    NASA Astrophysics Data System (ADS)

    Petryk, Alicia Ailie

    Magnetic nanoparticle hyperthermia (mNPH) is an emerging cancer therapy which has shown to be most effective when applied in the adjuvant setting with chemotherapy, radiation or surgery. Although mNPH employs heat as a primary therapeutic modality, conventional heat may not be the only cytotoxic effect. As such, my studies have focused on the mechanism and use of mNPH alone and in conjunction with cisplatinum chemotherapy in murine breast cancer cells and a related in vivo model. MNPH was compared to conventional microwave tumor heating, with results suggesting that mNPH (mNP directly injected into the tumor and immediately activated) and 915 MHz microwave hyperthermia, at the same thermal dose, result in similar tumor regrowth delay kinetics. However, mNPH shows significantly less peri-tumor normal tissue damage. MNPH combined with cisplatinum also demonstrated significant improvements in regrowth delay over either modality applied as a monotherapy. Additional studies demonstrated that a relatively short tumor incubation time prior to AMF exposure (less than 10 minutes) as compared to a 4-hour incubation time, resulted in faster heating rates, but similar regrowth delays when treated to the same thermal dose. The reduction of heating rate correlated well with the observed reduction in mNP concentration in the tumor observed with 4 hour incubation. The ability to effectively deliver cytotoxic mNPs to metastatic tumors is the hope and goal of systemic mNP therapy. However, delivering relevant levels of mNP is proving to be a formidable challenge. To address this issue, I assessed the ability of cisplatinum to simultaneously treat a tumor and improve the uptake of systemically delivered mNPs. Following a cisplatinum pretreatment, systemic mNPs uptake was increased by 3.1 X, in implanted murine breast tumors. Additional in vitro studies showed the necessity of a specific mNP/ Fe architecture and spatial relation for heat-based cytotoxicity in cultured cells.

  20. Adjuvant chemotherapy for endometrial cancer after hysterectomy

    PubMed Central

    Johnson, Nick; Bryant, Andrew; Miles, Tracie; Hogberg, Thomas; Cornes, Paul

    2014-01-01

    Background Endometrial adenocarcinoma (womb cancer) is a malignant growth of the lining (endometrium) of the womb (uterus). It is distinct from sarcomas (tumours of the uterine muscle). Survival depends the risk of microscopic metastases after surgery. Adjuvant (postoperative) chemotherapy improves survival from some other adenocarcinomas, and there is evidence that endometrial cancer is sensitive to cytotoxic therapy. This systematic review examines the effect of chemotherapy on survival after hysterectomy for endometrial cancer. Objectives To assess efficacy of adjuvant (postoperative) chemotherapy for endometrial cancer. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE up to August 2010, registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) comparing adjuvant chemotherapy with any other adjuvant treatment or no other treatment. Data collection and analysis We used a random-effects meta-analysis to assess hazard ratios (HR) for overall and progression-free survival and risk ratios (RR) to compare death rates and site of initial relapse. Main results Five RCTs compared no additional treatment with additional chemotherapy after hysterectomy and radiotherapy. Four trials compared platinum based combination chemotherapy directly with radiotherapy. Indiscriminate pooling of survival data from 2197 women shows a significant overall survival advantage from adjuvant chemotherapy (RR (95% CI) = 0.88 (0.79 to 0.99)). Sensitivity analysis focused on trials of modern platinum based chemotherapy regimens and found the relative risk of death to be 0.85 ((0.76 to 0.96); number needed to treat for an additional beneficial outcome (NNT) = 25; absolute risk reduction = 4% (1% to 8%)). The HR for overall survival is 0.74 (0.64 to 0.89), significantly

  1. Reducing psychological distress in patients undergoing chemotherapy.

    PubMed

    Milanti, Ariesta; Metsälä, Eija; Hannula, Leena

    Psychological distress is a common problem among patients with cancer, yet it mostly goes unreported and untreated. This study examined the association of a psycho-educational intervention with the psychological distress levels of breast cancer and cervical cancer patients undergoing chemotherapy. The design of the study was quasi-experimental, pretest-posttest design with a comparison group. One hundred patients at a cancer hospital in Jakarta, Indonesia, completed Distress Thermometer screening before and after chemotherapy. Fifty patients in the intervention group were given a psycho-educational video with positive reappraisal, education and relaxation contents, while receiving chemotherapy. Patients who received the psycho-educational intervention had significantly lower distress levels compared with those in the control group. Routine distress screening, followed by distress management and outcome assessment, is needed to improve the wellbeing of cancer patients. PMID:26911178

  2. MAPK-ERK activation in kidney of male rats chronically fed ochratoxin A at a dose causing a significant incidence of renal carcinoma

    SciTech Connect

    Marin-Kuan, M. Nestler, S.; Verguet, C.; Bezencon, C.; Piguet, D.; Delatour, T.; Mantle, P.; Cavin, C.; Schilter, B.

    2007-10-15

    Kidney samples of male Fischer 344 (F-344) rats fed a carcinogenic dose of OTA over 7 days, 21 days and 12 months were analysed for various cell signalling proteins known to be potentially involved in chemical carcinogenicity. OTA was found to increase the phosphorylation of atypical-PKC. This was correlated with a selective downstream activation of the MAP-kinase extracellular regulated kinases isoforms 1 and 2 (ERK1/2) and of their substrates ELK1/2 and p90RSK. Moreover, analysis of effectors acting upstream of PKC indicated a possible mobilisation of the insulin-like growth factor-1 receptor (lGFr) and phosphoinositide-dependent kinase-1 (PDK1) system. An increased histone deacetylase (HDAC) enzymatic activity associated with enhanced HDAC3 protein expression was also observed. These findings are potentially relevant with respect to the understanding of OTA nephrocarcinogenicity. HDAC-induced gene silencing has previously been shown to play a role in tumour development. Furthermore, PKC and the MEK-ERK MAP-kinase pathways are known to play important roles in cell proliferation, cell survival, anti-apoptotic activity and renal cancer development.

  3. Influence of definitive radiation therapy for primary breast cancer on ability to deliver adjuvant chemotherapy

    SciTech Connect

    Lippman, M.E.; Edwards, B.K.; Findlay, P.; Danforth, D.W. Jr.; MacDonald, H.; D'Angelo, T.; Gorrell, C.

    1986-01-01

    Primary radiotherapy as a means of managing stage I and II breast cancer is receiving increasing attention. In a prospectively randomized trial comparing modified radical mastectomy to lumpectomy followed by definitive radiotherapy, we evaluated whether radiotherapy has a deleterious effect on the ability to administer adjuvant doxorubicin and cyclophosphamide to patients with histologically positive axillary lymph nodes. All patients were treated with an identical regimen, and doses were escalated to the same degree until myelosuppression occurred. There were no significant differences in the amount of chemotherapy administered to either treatment group. Patients in both groups received approximately 100% of the predicted dose of doxorubicin and approximately 117% of the predicted dose of cyclophosphamide. At present, we have no evidence that there are differences in recurrence rates as a function of the quantity of drug received, although longer follow-up is required.

  4. Preventing medication errors in cancer chemotherapy.

    PubMed

    Cohen, M R; Anderson, R W; Attilio, R M; Green, L; Muller, R J; Pruemer, J M

    1996-04-01

    Recommendations for preventing medication errors in cancer chemotherapy are made. Before a health care provider is granted privileges to prescribe, dispense, or administer antineoplastic agents, he or she should undergo a tailored educational program and possibly testing or certification. Appropriate reference materials should be developed. Each institution should develop a dose-verification process with as many independent checks as possible. A detailed checklist covering prescribing, transcribing, dispensing, and administration should be used. Oral orders are not acceptable. All doses should be calculated independently by the physician, the pharmacist, and the nurse. Dosage limits should be established and a review process set up for doses that exceed the limits. These limits should be entered into pharmacy computer systems, listed on preprinted order forms, stated on the product packaging, placed in strategic locations in the institution, and communicated to employees. The prescribing vocabulary must be standardized. Acronyms, abbreviations, and brand names must be avoided and steps taken to avoid other sources of confusion in the written orders, such as trailing zeros. Preprinted antineoplastic drug order forms containing checklists can help avoid errors. Manufacturers should be encouraged to avoid or eliminate ambiguities in drug names and dosing information. Patients must be educated about all aspects of their cancer chemotherapy, as patients represent a last line of defense against errors. An interdisciplinary team at each practice site should review every medication error reported. Pharmacists should be involved at all sites where antineoplastic agents are dispensed. Although it may not be possible to eliminate all medication errors in cancer chemotherapy, the risk can be minimized through specific steps. Because of their training and experience, pharmacists should take the lead in this effort. PMID:8697025

  5. Oculomotor Deficits after Chemotherapy in Childhood.

    PubMed

    Einarsson, Einar-Jón; Patel, Mitesh; Petersen, Hannes; Wiebe, Thomas; Magnusson, Måns; Moëll, Christian; Fransson, Per-Anders

    2016-01-01

    Advances in the diagnosis and treatment of pediatric malignancies have substantially increased the number of childhood cancer survivors. However, reports suggest that some of the chemotherapy agents used for treatment can cross the blood brain barrier which may lead to a host of neurological symptoms including oculomotor dysfunction. Whether chemotherapy at young age causes oculomotor dysfunction later in life is unknown. Oculomotor performance was assessed with traditional and novel methods in 23 adults (mean age 25.3 years, treatment age 10.2 years) treated with chemotherapy for a solid malignant tumor not affecting the central nervous system. Their results were compared to those from 25 healthy, age-matched controls (mean age 25.1 years). Correlation analysis was performed between the subjective symptoms reported by the chemotherapy treated subjects (CTS) and oculomotor performance. In CTS, the temporal control of the smooth pursuit velocity (velocity accuracy) was markedly poorer (p<0.001) and the saccades had disproportionally shorter amplitude than normal for the associated saccade peak velocity (main sequence) (p = 0.004), whereas smooth pursuit and saccade onset times were shorter (p = 0.004) in CTS compared with controls. The CTS treated before 12 years of age manifested more severe oculomotor deficits. CTS frequently reported subjective symptoms of visual disturbances (70%), unsteadiness, light-headedness and that things around them were spinning or moving (87%). Several subjective symptoms were significantly related to deficits in oculomotor performance. To conclude, chemotherapy in childhood or adolescence can result in severe oculomotor dysfunctions in adulthood. The revealed oculomotor dysfunctions were significantly related to the subjects' self-perception of visual disturbances, dizziness, light-headedness and sensing unsteadiness. Assessments of oculomotor function may, thus, offer an objective method to track and rate the level of neurological

  6. Oculomotor Deficits after Chemotherapy in Childhood

    PubMed Central

    Einarsson, Einar-Jón; Patel, Mitesh; Petersen, Hannes; Wiebe, Thomas; Magnusson, Måns; Moëll, Christian; Fransson, Per-Anders

    2016-01-01

    Advances in the diagnosis and treatment of pediatric malignancies have substantially increased the number of childhood cancer survivors. However, reports suggest that some of the chemotherapy agents used for treatment can cross the blood brain barrier which may lead to a host of neurological symptoms including oculomotor dysfunction. Whether chemotherapy at young age causes oculomotor dysfunction later in life is unknown. Oculomotor performance was assessed with traditional and novel methods in 23 adults (mean age 25.3 years, treatment age 10.2 years) treated with chemotherapy for a solid malignant tumor not affecting the central nervous system. Their results were compared to those from 25 healthy, age-matched controls (mean age 25.1 years). Correlation analysis was performed between the subjective symptoms reported by the chemotherapy treated subjects (CTS) and oculomotor performance. In CTS, the temporal control of the smooth pursuit velocity (velocity accuracy) was markedly poorer (p<0.001) and the saccades had disproportionally shorter amplitude than normal for the associated saccade peak velocity (main sequence) (p = 0.004), whereas smooth pursuit and saccade onset times were shorter (p = 0.004) in CTS compared with controls. The CTS treated before 12 years of age manifested more severe oculomotor deficits. CTS frequently reported subjective symptoms of visual disturbances (70%), unsteadiness, light-headedness and that things around them were spinning or moving (87%). Several subjective symptoms were significantly related to deficits in oculomotor performance. To conclude, chemotherapy in childhood or adolescence can result in severe oculomotor dysfunctions in adulthood. The revealed oculomotor dysfunctions were significantly related to the subjects’ self-perception of visual disturbances, dizziness, light-headedness and sensing unsteadiness. Assessments of oculomotor function may, thus, offer an objective method to track and rate the level of neurological

  7. Chemotherapy-induced polyneuropathy. Part I. Pathophysiology

    PubMed Central

    2012-01-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is a toxic neuropathy, a syndrome consisting of highly distressing symptoms of various degrees of severity. It includes numbness of distal extremities, long-term touch, heat, and cold dysaesthesia and, in more severe cases, motor impairment affecting daily functioning. Each form of the syndrome may be accompanied by symptoms of neuropathic stinging, burning, and tingling pain. In the case of most chemotherapeutic agents, the incidence and severity of CIPN are dependent on the cumulative dose of the drug. The syndrome described is caused by damage to the axons and/or cells of the peripheral nervous system. Chemotherapeutic agents have distinct mechanisms of action in both neoplastic tissue and the peripheral nervous system; therefore, CIPN should not be regarded as a homogeneous disease entity. The present article is an attempt to systematize the knowledge about the toxic effects of chemotherapy on the peripheral nervous system. PMID:23788859

  8. [Scalp cooling for chemotherapy-induced alopecia].

    PubMed

    Komen, Marion M C; Smorenburg, Carolien H; van den Hurk, Corina J G; Nortier, J W R Hans

    2011-01-01

    Alopecia is a very common side effect of cytostatic therapy and is considered one of the most emotionally distressing effects. To prevent alopecia scalp cooling is currently used in some indications in medical oncology in 59 hospitals in the Netherlands. The success of scalp cooling depends on various factors such as type of chemotherapy, dose, infusion time, number of treatment cycles and combinations of drugs. In general, scalp cooling is well tolerated. The reported side-effects are headache, coldness, dizziness and sometimes claustrophobia. An increase in the risk of scalp metastases has not been demonstrated. Proceeding from the South Netherlands Comprehensive Cancer Centre a national working group is put together in order to draw up a national guideline for chemotherapy-induced alopecia. PMID:22085565

  9. Toxicity profile and clinical outcomes in locally advanced head and neck cancer patients treated with induction chemotherapy prior to concurrent chemoradiation.

    PubMed

    Ko, Eric C; Genden, Eric M; Misiukiewicz, Krzysztof; Som, Peter M; Kostakoglu, Lale; Chen, Chien-Ting; Packer, Stuart; Kao, Johnny

    2012-02-01

    The use of induction chemotherapy prior to chemoradiation for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) remains controversial. We explored whether toxicity from induction chemotherapy influenced the delivery of concurrent chemoradiation. Among 171 consecutive previously unirradiated patients with HNSCC treated with combined chemotherapy and radiation, we identified 66 patients with stage III-IVB head and neck carcinoma who were treated with induction chemotherapy prior to planned chemoradiation. The most common induction regimen was docetaxel, cisplatin and 5-FU (TPF; 80%) for 2 to 3 cycles. Mean radiation dose was 72 Gy (range, 36-75 Gy). Concurrent chemotherapy regimens included cisplatin (26%), cetuximab (5%) and 5-fluorouracil/hydroxyurea (65%)-based regimens. At a median follow-up of 27 months (range, 9-56 months), the 2-year locoregional control and distant control rates were 85 and 86%, respectively. The 2-year disease-free survival and overall survival rates were 74 and 80%, respectively. Although there were no grade 5 toxicities during induction chemotherapy, 26% of patients required hospitalization for adverse events, including 5% needing intensive care. The most common high grade adverse events were grade 4 neutropenia (21%) and neutropenic fever (17%). Six percent of patients were unable to tolerate concurrent chemotherapy. The 2-year disease-free survival was significantly higher in patients able to complete induction and concurrent chemoradiation as planned (83 vs. 27%, p<0.001). Induction chemotherapy followed by concurrent chemoradiation results in promising survival rates in our cohort of advanced head and neck carcinoma patients. Due to severe toxicities in a subset of patients, this strategy is only recommended in selected high-risk patients who are carefully followed by an experienced multidisciplinary team. PMID:22020564

  10. Design of the EXercise Intervention after Stem cell Transplantation (EXIST) study: a randomized controlled trial to evaluate the effectiveness and cost-effectiveness of an individualized high intensity physical exercise program on fitness and fatigue in patients with multiple myeloma or (non-) Hodgkin's lymphoma treated with high dose chemotherapy and autologous stem cell transplantation

    PubMed Central

    2010-01-01

    Background The use of high-dose chemotherapy combined with autologous stem cell transplantation has improved the outcome of hematologic malignancies. Nevertheless, this treatment can cause persistent fatigue and a reduced global quality of life, role and physical function. Physical exercise interventions may be beneficial for physical fitness, fatigue and quality of life. However, the trials conducted so far to test the effects of physical exercise interventions in this group of patients were of poor to moderate methodological quality and economic evaluations are lacking. Hence there is need for a rigorous, appropriately controlled assessment of the effectiveness of exercise programs in these patients. The aims of the present study are (1) to determine the effectiveness of an individualized high intensity strength and interval training program with respect to physiological and psychological health status in patients with multiple myeloma or (non-)Hodgkin's lymphoma who have recently undergone high dose chemotherapy followed by autologous stem cell transplantation; and (2) to evaluate the cost-effectiveness of this program. Methods A multicenter, prospective, single blind randomized controlled trial will be performed. We aim to recruit 120 patients within an inclusion period of 2 years at 7 hospitals in the Netherlands. The patients will be randomly assigned to one of two groups: (1) intervention plus usual care; or (2) usual care. The intervention consists of an 18-week individualized supervised high-intensity exercise program and counselling. The primary outcomes (cardiorespiratory fitness, muscle strength and fatigue) and secondary outcomes are assessed at baseline, at completion of the intervention and at 12 months follow-up. Discussion The strengths of this study include the solid trial design with clearly defined research groups and standardized outcome measures, the inclusion of an economic evaluation and the inclusion of both resistance and endurance

  11. Radiation Therapy Oncology Group Protocol 02-29: A Phase II Trial of Neoadjuvant Therapy With Concurrent Chemotherapy and Full-Dose Radiation Therapy Followed by Surgical Resection and Consolidative Therapy for Locally Advanced Non-small Cell Carcinoma of the Lung

    SciTech Connect

    Suntharalingam, Mohan; Paulus, Rebecca; Edelman, Martin J.; Krasna, Mark; Burrows, Whitney; Gore, Elizabeth; Wilson, Lynn D.; Choy, Hak

    2012-10-01

    Purpose: To evaluate mediastinal nodal clearance (MNC) rates after induction chemotherapy and concurrent, full-dose radiation therapy (RT) in a phase II trimodality trial (Radiation Therapy Oncology Group protocol 0229). Patients and Methods: Patients (n=57) with stage III non-small cell lung cancer (pathologically proven N2 or N3) were eligible. Induction chemotherapy consisted of weekly carboplatin (AUC = 2.0) and paclitaxel 50 mg/m{sup 2}. Concurrent RT was prescribed, with 50.4 Gy to the mediastinum and primary tumor and a boost of 10.8 Gy to all gross disease. The mediastinum was pathologically reassessed after completion of chemoradiation. The primary endpoint of the study was MNC, with secondary endpoints of 2-year overall survival and postoperative morbidity/mortality. Results: The grade 3/4 toxicities included hematologic 35%, gastrointestinal 14%, and pulmonary 23%. Forty-three patients (75%) were evaluable for the primary endpoint. Twenty-seven patients achieved the primary endpoint of MNC (63%). Thirty-seven patients underwent resection. There was a 14% incidence of grade 3 postoperative pulmonary complications and 1 30-day, postoperative grade 5 toxicity (3%). With a median follow-up of 24 months for all patients, the 2-year overall survival rate was 54%, and the 2-year progression-free survival rate was 33%. The 2-year overall survival rate was 75% for those who achieved nodal clearance, 52% for those with residual nodal disease, and 23% for those who were not evaluable for the primary endpoint (P=.0002). Conclusions: This multi-institutional trial confirms the ability of neoadjuvant concurrent chemoradiation with full-dose RT to sterilize known mediastinal nodal disease.

  12. Chemotherapy tolerance after radioimmunotherapy with 90Y-CC49 monoclonal antibody in patients with advanced non-small cell lung cancer: clinical effects and hematologic toxicity.

    PubMed

    Robert, Francisco; Busby, Elizabeth M; LoBuglio, Albert F

    2003-06-01

    The purpose of this retrospective analysis was to evaluate the hematologic toxicity and clinical outcome of salvage chemotherapy following (90)Y-CC49 radioimmunotherapy (RIT) in patients with non-small cell lung cancer (NSCLC). Sixteen patients from a total of 37 who were enrolled in a phase I trial of (90)Y-CC49 monoclonal therapy were treated with post-RIT salvage chemotherapy at our institution. Five patients had received chest radiation therapy prior to RIT, and seven patients had prior chemotherapy. The majority of these patients were treated with doses of (90)Y of >/= 14 mCi/m(2) (8-20 mCi/m(2)), and four of them received concurrent 96-hour taxol infusion. The maximum tolerated dose of this study was exceeded at 17 mCi/m(2), and grade 4 thrombocytopenia/neutropenia were the dose-limiting toxicities. Twelve patients received one chemotherapy regimen as salvage therapy, and four patients had more than one regimen. Four patients (25%) experienced reversible grade 4 neutropenia, but no grade 4 thrombocytopenia was observed. Five patients had stable disease. The median survival from start of salvage therapy was 5.5 months. Our data suggest that therapy with RIT did not significantly affect survival of these patients. Taking into consideration the potential clinical relevance of integration of RIT with other treatment modalities, it is important to expand this clinical experience in order to support combined modality strategies. PMID:12954119

  13. Epoetin Theta in Anaemic Cancer Patients Receiving Platinum-Based Chemotherapy: A Randomised Controlled Trial

    PubMed Central

    Tjulandin, Sergei A; Bias, Peter; Elsässer, Reiner; Gertz, Beate; Kohler, Erich; Buchner, Anton

    2010-01-01

    Introduction Recombinant human erythropoietin (r-HuEPO) is used to treat symptomatic anaemia due to chemotherapy. A new r-HuEPO, Epoetin theta (Eporatio®), was investigated and compared to placebo and Epoetin beta in a randomised, double-blind clinical trial in adult cancer patients receiving platinum-based chemotherapy, using a fixed weekly starting dose of 20,000 IU Epoetin theta. The primary efficacy endpoint was the responder rate (complete Hb response, Hb increase ≥ 2 g/dL). Research Design and Methods 223 patients were randomised to s.c. treatment for 12 weeks with either Epoetin theta (n = 76) once per week, Epoetin beta (n = 73) three times per week or placebo (n = 74). The starting dose was 20,000 IU once weekly Epoetin theta or 450 IU/kgBW per week Epoetin beta administered in 3 equal weekly doses. Results In the Epoetin theta group were significantly more responders than in the placebo group (65.8 vs. 20.3%, P < 0.0001). Epoetin beta was also more effective than placebo (71.2 vs. 20.3%, P < 0.0001). The mean weekly dose at the time of complete Hb response was lower in the Epoetin theta group (30,000 IU) than in the Epoetin beta group (42,230 IU). Epoetin theta was clearly more effective than placebo. Conclusion This small study showed, that Epoetin theta is a safe and effective treatment of symptomatic anaemia due to platinum-based chemotherapy in cancer patients. PMID:21331363

  14. Delay of the Blink Reflex in Patients Receiving Platinum-Analogue Chemotherapy

    PubMed Central

    Park, Kang Young; Park, Yun Hee; Chang, Hyun Jung; Cho, Eun Sol; Kim, Seok-Hyun; Kim, Woo Jin

    2016-01-01

    Objective To investigate the presence of cranial neuropathy in patients with platinum-analogue chemotherapy using electrodiagnostic evaluations. Methods Thirty-nine patients whose chemotherapy was completed within a month and 40 control subjects were enrolled in the study. Electrodiagnostic evaluation was performed using sensory and motor nerve conduction studies and blink reflex studies, in addition to the two-point discrimination test. Results The chemotherapy group had significantly longer latencies of bilateral R1 responses (left p<0.001; right p<0.001) and greater distance in two-point discrimination (p<0.001) compared to the control group. In the subgroup with peripheral polyneuropathy, the left R1 (p=0.01), both R2i (left p=0.02; right p=0.03) and the left R2c (p=0.02) were prolonged relative to those without the polyneuropathy, and both R1 (left p<0.001; right p<0.001), R2i (left p=0.01; right p=0.03), and the left R2c (p=0.01) were prolonged relative to the controls. On the other hand, the subgroup without the polyneuropathy showed only prolongation of both R1 (left p=0.006; right p<0.001) relative to the controls. Conclusion In the present study, comparison of blink reflex and two-point discrimination showed the likelihood of subclinical cranial neuropathy following platinum-analogue chemotherapy. Cranial neuropathy caused by platinum agents was more profound in patients with peripheral polyneuropathy and may be dependent on the cumulative dose of the drug. The blink reflex may be of value in detecting subclinical cranial neuropathy in patients undergoing platinum-analogue chemotherapy. PMID:26949671

  15. Cataracts after total body irradiation and marrow transplantation: a sparing effect of dose fractionation

    SciTech Connect

    Deeg, H.J.; Flournoy, N.; Sullivan, K.M.; Sheehan, K.; Buckner, C.D.; Sanders, J.E.; Storb, R.; Witherspoon, R.P.; Thomas, E.D.

    1984-07-01

    Two hundred seventy-seven patients, who have been followed for 1 to 12 years after marrow transplantation, have been examined for cataract development. In preparation for transplantation, 96 patients with aplastic anemia were conditioned with chemotherapy only, while 181 patients (two with aplastic anemia and 179 with a hematologic malignancy) were conditioned with a regimen of total body irradiation (TBI) and chemotherapy. TBI was delivered from two opposing /sup 60/Co sources at an exposure rate of 4 to 8 cGy/min, either as a single dose of 10 Gy (105 patients) or in fractions (76 patients). To date, 86 patients have developed cataracts. Kaplan-Meier product limit estimates of the incidence of cataracts for patients given chemotherapy only and no TBI, single-dose TBI, and fractionated TBI are 19, 80, 18%, respectively. On the basis of proportional hazards regression analyses, patients given single-dose TBI had a relative risk of developing cataracts that was 4.7-fold higher than in patients given fractionated TBI or chemotherapy only, suggesting a significant sparing effect with use of TBI dose fractionation.

  16. Chemotherapy-induced neutropenia among pediatric cancer patients in Egypt: Risks and consequences

    PubMed Central

    Badr, Mohamed; Hassan, Tamer; Sakr, Hanan; Karam, Nehad; Rahman, Doaa Abdel; Shahbah, Doaa; Zakaria, Marwa; Fehr, Sahbaa

    2016-01-01

    Chemotherapy-induced neutropenia (CIN) is the major dose-limiting toxicity of systemic chemotherapy and it is associated with significant morbidity, mortality and treatment cost. The aim of the present study was to identify the risk factors that may predispose pediatric cancer patients who receive myelosuppressive chemotherapy to CIN and associated sequelae. A total of 113 neutropenia episodes were analyzed and the risk factors for CIN were classified as patient-specific, disease-specific and regimen-specific, while the consequences of CIN were divided into infectious and dose-modifying sequelae. The risks and consequences were analyzed to target high-risk patients with appropriate preventive strategies. Among our patients, 28% presented with a single neutropenia attack, while 72% experienced recurrent attacks during their treatment cycles. The mean absolute neutrophil count was 225.5±128.5 ×109/l (range, 10–497 ×109/l), starting 14.2±16.3 days (range, 2–100 days) after the onset of chemotherapy and resolving within 11.2±7.3 days, either with (45.1%) or without (54.9%) granulocyte colony-stimulating factor (G-CSF). No significant association was observed between any patient characteristics or disease stage and the risk for CIN. However, certain malignancies, such as acute lymphocytic leukemia (ALL), neuroblastoma and Burkitt's lymphoma, and certain regimens, such as induction block for ALL and acute myelocytic leukemia, exerted the most potent myelotoxic effect, with severe and prolonged episodes of neutropenia. G-CSF significantly shortened the duration of the episodes and enhanced bone marrow recovery. Febrile neutropenia was the leading complication among our cases (73.5%) and was associated with several documented infections, particularly mucositis (54.9%), respiratory (45.1%), gastrointestinal tract (38.9%) and skin (23.9%) infections. A total of 6% of our patients succumbed to infection-related complications. Neutropenia was responsible for treatment

  17. Chemotherapy-induced oral mucositis: new approaches to prevention and management.

    PubMed

    Wright, Janice; Feld, Ronald; Knox, Jennifer

    2005-03-01

    Oral mucositis is a common and significant toxicity of cancer chemotherapy. It is under-reported and not well treated, particularly in patients that receive high-dose therapy with an autologous or allogenic stem cell transplant. Two recently published retrospective analyses of patient complaints following stem cell transplantation have identified oral mucositis as the worst toxicity reported by patients, and what is more important is that patients indicated that oncology healthcare team members do a poor job of managing and providing methods of symptom relief. Twenty percent of patients surveyed indicated they received no symptom relief at all. PMID:15794713

  18. Survival outcomes and toxicity of intraoperative intraperitoneal chemotherapy in advanced epithelial ovarian cancer

    PubMed Central

    Yoon, Ji-Young; Koo, Yu-Jin; Kim, Mi-Jung; Kim, Tae-Jin; Lim, Kyung-Taek

    2014-01-01

    Objective To assess the effect of single-dose cisplatin intraperitoneally administered during cytoreductive surgery in advanced epithelial ovarian cancer. Methods Data from patients who underwent surgical management followed by intravenous (IV) chemotherapy for stage III epithelial ovarian cancer from 2003 to 2012 were retrospectively reviewed. Subjects were divided into intraperitoneal (IP) and no-intraperitoneal (NIP) groups according to the administration of IP cisplatin 100 mg during the staging surgery. Clinical results such as survival outcomes and chemotherapeutic toxicity were compared between the two groups. Results Thirty-seven patients in the IP group and 26 in the NIP group were identified. There were no significant differences between the two groups in basic characteristics such as age, histology, and surgical procedures. After the surgery with or without IP chemotherapy, there was no difference in the rate of either hematologic or gastrointestinal toxicity or in the rate of incompletion of following IV chemotherapy. Tumor recurrence occurred in 67.6% (25 patients) of IP group and 57.7% (15 patients) of NIP group (P=0.423) during the mean follow-up period of 37 months. The 3-year disease free-survival rate was 39.9% in the IP group and 35.8% in the NIP group, and the relative risk of recurrence was 0.864 (95% confidence interval, 0.447-1.673; P=0.665) in the IP group as compared with the NIP group. Conclusion IP chemotherapy with single-dose cisplatin during cytoreductive surgery is safe and feasible with little chemotherapeutic toxicity in advanced epithelial ovarian cancer, but no distinct improvement in survival could be demonstrated in the present study. PMID:25469337

  19. Cisplatin based chemotherapy in testicular cancer patients: long term platinum excretion and clinical effects.

    PubMed

    Hohnloser, J H; Schierl, R; Hasford, B; Emmerich, B

    1996-09-20

    Patients with advanced testicular cancer (TC) have a very good long-term prognosis owing to cisplatin-based polychemotherapy. Platinum is believed to be excreted at a rapid rate via urine within weeks after chemotherapy. As a new, highly sensitive method has become available detecting even natural background platinum levels in body fluids, this study was set up to analyze urinary and serum platinum levels in long-term survivors of testicular neoplasm after cisplatin based polychemotherapy and to correlate clinical data with urinary and serum platinum levels. Urinary platinum concentrations were measured in 64 healthy controls (C) and 22 male patients (TC) 150 to 3022 days after the last application of i.v. cisplatin using voltammetry after UV-photolysis. In the latter group (TC), serum platinum levels were measured as well. Clinical data were analysed as to long-term organ toxicity. Mean urinary platinum levels were 2700 times higher in the patient group (TC) than natural background noise (p < 0.0001). There was a decline of urinary and serum platinum levels over time, being significantly above normal even 8 years after cisplatin exposure. The only significant variables related to the urine platinum concentration were a) the interval between the last i.v. cisplatin application and time of study and b) the total dose given. Not significant were the number of chemotherapy cycles, pre-therapy renal disease, patient age, tumour resection before/after chemotherapy, site of pre/post therapy resection, clinical staging, histological subtypes or tumour markers. Post-therapy renal disease or peripheral nerve damage were not significantly associated with urinary platinum levels. Our data indicate that even 8 years after cisplatin based chemotherapy 500 times elevated urinary and serum platinum levels can be measured in testicular cancer patients. No organ toxicity related to long-term platinum excretion could be detected. This may be due to our small sample size. PMID

  20. Pharmacokinetics of high-dose busulfan in children.

    PubMed

    Vassal, G; Gouyette, A; Hartmann, O; Pico, J L; Lemerle, J

    1989-01-01

    The pharmacokinetics of high-dose busulfan given orally at 1 mg/kg every 6 h over 4 days (total dose, 16 mg/kg) in combined chemotherapy followed by autologous bone marrow transplantation was studied in 12 children with a mean age of 7 years (range, 4-14 years). Busulfan levels in biological fluids were measured by a gas chromatographic assay with mass fragmentographic detection, using a deuterated analogue as the internal standard. In a high-dose regimen, busulfan followed one-compartment model kinetics with zero-order absorption. A mean maximal concentration of 803 +/- 228 ng/ml was achieved at 92-255 min after dosing. The mean elimination half-life was 2.33 h, and the mean total clearance was 119 +/- 54 ml/min per m2, with an apparent distribution volume of 27.10 +/- 11.50 l/m2. A mean trough level of 370 ng/ml was found throughout the 4 days of the chemotherapy course. There were no significant variations in pharmacokinetic parameters measured after the first and last doses. Busulfan was monitored in the CSF of nine children at 3.25-7 h after the last dose and was detected in all patients, with a mean CSF-to-plasma concentration ratio of 0.95 (range, 0.5-1.4). PMID:2791192

  1. Preradiation chemotherapy may improve survival in pediatric diffuse intrinsic brainstem gliomas: Final results of BSG 98 prospective trial

    PubMed Central

    Frappaz, Didier; Schell, Matthias; Thiesse, Philippe; Marec-Bérard, Perrine; Mottolese, Carmine; Perol, David; Bergeron, Christophe; Philip, Thierry; Ricci, Anne Claire; Galand-Desme, Sophie; Szathmari, Alexandru; Carrie, Christian

    2008-01-01

    Radiation therapy remains the only treatment that provides clinical benefit to children with diffuse brainstem tumors. Their median survival, however, rarely exceeds 9 months. The authors report a prospective trial of front-line chemotherapy aimed at delaying radiation until time of clinical progression. The aim was to investigate the possibility that radiotherapy would maintain its activity in children whose disease progressed after chemotherapy. Twenty-three patients took part in this protocol, the BSG 98 protocol, which consisted of frontline chemotherapy alternating hematotoxic and nonhematotoxic schedules. Each cycle included three courses delivered monthly; the first course was 1,3-bis(2-chloroethyl)-1-nitrosourea– cisplatin, and the second and third were high-dose methotrexate. Three patients underwent one cycle; 5 patients each, two and three cycles; and 10 patients, four cycles. Twenty of the 23 patients eventually received local radiation therapy. A historical cohort of 14 patients who received at least local radiation therapy served as controls. Four patients experienced severe iatrogenic infections, and 11 patients required platelet transfusions. Median survival increased significantly in patients participating in the protocol compared to that in the historical controls (17 months, 95% confidence interval [CI], 10–23 months, vs. 9 months, 95% CI, 8–10 months; p = 0.022), though hospitalization was prolonged (57 vs. 25 days, p = 0.001). Although frontline chemotherapy alternating hematotoxic and nonhematotoxic schedules significantly increases overall median survival, its cost from infection and hospitalization deserves honest discussion with the children and their parents. PMID:18577561

  2. Chemotherapy-related toxicity in patients with non-metastatic Ewing sarcoma: influence of sex and age.

    PubMed

    Paioli, Anna; Luksch, Roberto; Fagioli, Franca; Tamburini, Angela; Cesari, Marilena; Palmerini, Emanuela; Abate, Massimo Eraldo; Marchesi, Emanuela; Balladelli, Alba; Pratelli, Loredana; Ferrari, Stefano

    2014-02-01

    Influence of age and sex on chemotherapy-related toxicity was evaluated in children (3-9 years), adolescents (10-17 years), and adults (up to 40 years) with localized Ewing sarcoma (ES) enrolled in the ISG/SSG III protocol. Treatment was based on vincristine, doxorubicin, cyclophosphamide, ifosfamide, dactinomycin, and etoposide. High-dose chemotherapy with busulfan and melphalan was given in poor responder patients. The analysis was based on 2191 courses of standard chemotherapy and 230 patients. A lower risk of G4 leukopenia and thrombocytopenia, hospitalization, febrile neutropenia, and red blood cell (RBC) transfusions was observed in males. Use of granulocyte colony-stimulating factor (G-CSF) was more frequent in adults, while children more often received RBC transfusions. A significant correlation between sex and chemotherapy-related toxicity was observed in the study, whereas no significant differences in terms of bone marrow toxicity can be expected according to patient age. Further studies should analyse the role of pharmacokinetics, pharmacogenomics, and clinical characteristics. PMID:24091100

  3. A combination of spatial and recursive temporal filtering for noise reduction when using region of interest (ROI) fluoroscopy for patient dose reduction in image guided vascular interventions with significant anatomical motion

    NASA Astrophysics Data System (ADS)

    Setlur Nagesh, S. V.; Khobragade, P.; Ionita, C.; Bednarek, D. R.; Rudin, S.

    2015-03-01

    Because x-ray based image-guided vascular interventions are minimally invasive they are currently the most preferred method of treating disorders such as stroke, arterial stenosis, and aneurysms; however, the x-ray exposure to the patient during long image-guided interventional procedures could cause harmful effects such as cancer in the long run and even tissue damage in the short term. ROI fluoroscopy reduces patient dose by differentially attenuating the incident x-rays outside the region-of-interest. To reduce the noise in the dose-reduced regions previously recursive temporal filtering was successfully demonstrated for neurovascular interventions. However, in cardiac interventions, anatomical motion is significant and excessive recursive filtering could cause blur. In this work the effects of three noise-reduction schemes, including recursive temporal filtering, spatial mean filtering, and a combination of spatial and recursive temporal filtering, were investigated in a simulated ROI dose-reduced cardiac intervention. First a model to simulate the aortic arch and its movement was built. A coronary stent was used to simulate a bioprosthetic valve used in TAVR procedures and was deployed under dose-reduced ROI fluoroscopy during the simulated heart motion. The images were then retrospectively processed for noise reduction in the periphery, using recursive temporal filtering, spatial filtering and a combination of both. Quantitative metrics for all three noise reduction schemes are calculated and are presented as results. From these it can be concluded that with significant anatomical motion, a combination of spatial and recursive temporal filtering scheme is best suited for reducing the excess quantum noise in the periphery. This new noise-reduction technique in combination with ROI fluoroscopy has the potential for substantial patient-dose savings in cardiac interventions.

  4. A Combination of Spatial and Recursive Temporal Filtering for Noise Reduction when Using Region of Interest (ROI) Fluoroscopy for Patient Dose Reduction in Image Guided Vascular Interventions with Significant Anatomical Motion

    PubMed Central

    Nagesh, S.V. Setlur; Khobragade, P.; Ionita, C.; Bednarek, D.R; Rudin, S.

    2015-01-01

    Because x-ray based image-guided vascular interventions are minimally invasive they are currently the most preferred method of treating disorders such as stroke, arterial stenosis, and aneurysms; however, the x-ray exposure to the patient during long image-guided interventional procedures could cause harmful effects such as cancer in the long run and even tissue damage in the short term. ROI fluoroscopy reduces patient dose by differentially attenuating the incident x-rays outside the region-of-interest. To reduce the noise in the dose-reduced regions previously recursive temporal filtering was successfully demonstrated for neurovascular interventions. However, in cardiac interventions, anatomical motion is significant and excessive recursive filtering could cause blur. In this work the effects of three noise-reduction schemes, including recursive temporal filtering, spatial mean filtering, and a combination of spatial and recursive temporal filtering, were investigated in a simulated ROI dose-reduced cardiac intervention. First a model to simulate the aortic arch and its movement was built. A coronary stent was used to simulate a bio-prosthetic valve used in TAVR procedures and was deployed under dose-reduced ROI fluoroscopy during the simulated heart motion. The images were then retrospectively processed for noise reduction in the periphery, using recursive temporal filtering, spatial filtering and a combination of both. Quantitative metrics for all three noise reduction schemes are calculated and are presented as results. From these it can be concluded that with significant anatomical motion, a combination of spatial and recursive temporal filtering scheme is best suited for reducing the excess quantum noise in the periphery. This new noise-reduction technique in combination with ROI fluoroscopy has the potential for substantial patient-dose savings in cardiac interventions. PMID:26900203

  5. Human recombinant TSH preceding a therapeutic dose of radioiodine for multinodular goiters has no significant effect in the surge of TSH-receptor and TPO antibodies.

    PubMed

    Rubio, Ileana G S; Perone, Bruno H; Silva, Marcia N C; Knobel, Meyer; Medeiros-Neto, Geraldo

    2005-02-01

    Radioiodine (RAI) treatment has increasingly been used mostly in elderly patients with multinodular goiter (MNG) as an alternative for surgery. Recombinant human thyrotropin (rhTSH) has been demonstrated to increase the uptake of RAI and also to promote a more even distribution of radionuclide among the various nodules. We have compared the surge of autoantibodies to thyroid peroxidase (anti-TPO) and to the TSH receptor (TRAb) in two groups of patients with MNG. Group RAI (n = 15) received only RAI, and Group RAI+rhTSH (n = 15) received RAI 24 h after 0.45 mg of rhTSH intramuscularly. At baseline, all 30 patients had negative anti-TPO antibodies. After RAI, 16 patients (eight in each group) exhibited a positive anti-TPO test (range, 70-2359 U/mL). In the rhTSH-treated group, anti-TPO values were significantly higher (as compared to basal levels; p < 0.02) after 3 months of RAI treatment. After 12 months, the anti-TPO values decreased to lower but still positive concentrations in nine patients (Group RAI: three patients; Group RAI+rhTSH: five patients). Only one patient had a positive TRAb test at baseline (67.5% inhibition of the TSH binding). After RAI, positive TRAb values were present in 21/30 patients. After 6 months of RAI treatment, there was a significant increase of the TRAb values in Group RAI+rhTSH patients. After 12 months, only four patients had positive TRAb (Group RAI: three patients; Group RAI+rhTSH: one patient). Two patients, one of each group, had an elevation of free T4 levels and suppressed serum TSH values, indicating hyperthyroidism (Graves' disease). Bioassay of TSH receptor (TSHR) indicated absence of a significant elevation of cAMP in the medium before and after RAI treatment in all patients. Moreover, predominantly blocking TSHR autoantibodies were detected in six of the 30 patients (three of each group). Sera from these patients were able to reduce the TSH-stimulated cAMP generation by CHO cells. We conclude that the autoantibodies to the

  6. Gene therapy enhances chemotherapy tolerance and efficacy in glioblastoma patients

    PubMed Central

    Adair, Jennifer E.; Johnston, Sandra K.; Mrugala, Maciej M.; Beard, Brian C.; Guyman, Laura A.; Baldock, Anne L.; Bridge, Carly A.; Hawkins-Daarud, Andrea; Gori, Jennifer L.; Born, Donald E.; Gonzalez-Cuyar, Luis F.; Silbergeld, Daniel L.; Rockne, Russell C.; Storer, Barry E.; Rockhill, Jason K.; Swanson, Kristin R.; Kiem, Hans-Peter

    2014-01-01

    BACKGROUND. Temozolomide (TMZ) is one of the most potent chemotherapy agents for the treatment of glioblastoma. Unfortunately, almost half of glioblastoma tumors are TMZ resistant due to overexpression of methylguanine methyltransferase (MGMThi). Coadministration of O6-benzylguanine (O6BG) can restore TMZ sensitivity, but causes off-target myelosuppression. Here, we conducted a prospective clinical trial to test whether gene therapy to confer O6BG resistance in hematopoietic stem cells (HSCs) improves chemotherapy tolerance and outcome. METHODS. We enrolled 7 newly diagnosed glioblastoma patients with MGMThi tumors. Patients received autologous gene-modified HSCs following single-agent carmustine administration. After hematopoietic recovery, patients underwent O6BG/TMZ chemotherapy in 28-day cycles. Serial blood samples and tumor images were collected throughout the study. Chemotherapy tolerance was determined by the observed myelosuppression and recovery following each cycle. Patient-specific biomathematical modeling of tumor growth was performed. Progression-free survival (PFS) and overall survival (OS) were also evaluated. RESULTS. Gene therapy permitted a significant increase in the mean number of tolerated O6BG/TMZ cycles (4.4 cycles per patient, P < 0.05) compared with historical controls without gene therapy (n = 7 patients, 1.7 cycles per patient). One patient tolerated an unprecedented 9 cycles and demonstrated long-term PFS without additional therapy. Overall, we observed a median PFS of 9 (range 3.5–57+) months and OS of 20 (range 13–57+) months. Furthermore, biomathematical modeling revealed markedly delayed tumor growth at lower cumulative TMZ doses in study patients compared with patients that received standard TMZ regimens without O6BG. CONCLUSION. These data support further development of chemoprotective gene therapy in combination with O6BG and TMZ for the treatment of glioblastoma and potentially other tumors with overexpression of MGMT. TRIAL

  7. Clinical roundtable monograph: New data in emerging treatment options for chemotherapy-induced nausea and vomiting.

    PubMed

    Morrow, Gary R; Navari, Rudolph M; Rugo, Hope S

    2014-03-01

    Chemotherapy-induced nausea and vomiting (CINV) has long been one of the most troublesome adverse effects of chemotherapy, leading to significant detriments in quality of life and functioning, increased economic costs, and, in some cases, the discontinuation of effective cancer therapy. The past 2 decades have witnessed a dramatic increase in the number of effective antiemetic agents, with the introduction of the serotonin (5-hydroxytryptamine [5-HT₃]) receptor antagonists (ondansetron, granisetron, and palonosetron), the neurokinin-1 (NK₁) receptor antagonists (aprepitant and fosaprepitant), and the identification of other agents that have demonstrated efficacy against CINV, including corticosteroids. These agents often provide excellent control of emesis. Nausea, however, has proven more intractable, particularly in the days after administration of chemotherapy. Newer antiemetic agents under study may provide additional CINV control, particularly against delayed nausea. New agents undergoing review by the US Food and Drug Administration for the prevention of CINV include the novel NK₁ receptor antagonist rolapitant and a fixed-dose combination consisting of the novel NK₁ receptor antagonist netupitant and palonosetron (NEPA). Adherence to clinical practice guidelines has been shown to significantly improve CINV control. As antiemetic therapy continues to evolve, it will be important for clinicians to stay informed of new developments and changes in guidelines. PMID:24874107

  8. Neoadjuvant and Adjuvant Chemotherapy of Cervical Cancer.

    PubMed

    Mallmann, Peter; Mallmann, Christoph

    2016-01-01

    Neoadjuvant chemotherapy is indicated in patients who can tolerate the side effects of a chemotherapy and with preoperative presentation of one of the following clinical risk situations: bulky disease with a maximal tumor diameter of > 4 cm, suspicious lymph nodes in magnetic resonance imaging (MRI), computed tomography (CT) scan or endosonography, histopathologically confirmed lymph node metastasis, or histopathologically documented risk factors such as G3 and L1V1. A neoadjuvant chemotherapy followed by surgery should be performed with cisplatin at a dosage of > 25 mg/m2 per week and an application interval of < 14 days. The previously published data suggests an improved rate of complete resection and reduced incidences of positive lymph nodes and parametric infiltration. Accordingly, the percentage of patients in need for adjuvant radiochemotherapy after operation can be significantly reduced. Some studies demonstrated a prolongation of progression-free and overall survival. Following the previously published studies, adjuvant chemotherapy after operation or after radiochemotherapy has no significant effect on the overall survival and, following the current guidelines, should be avoided. PMID:27614740

  9. B-IGEV (bortezomib plus IGEV) versus IGEV before high-dose chemotherapy followed by autologous stem cell transplantation in relapsed or refractory Hodgkin lymphoma: a randomized, phase II trial of the Fondazione Italiana Linfomi (FIL).

    PubMed

    Balzarotti, Monica; Brusamolino, Ercole; Angelucci, Emanuele; Carella, Angelo Michele; Vitolo, Umberto; Russo, Eleonora; Congiu, Angelagiovanna; Gotti, Manuel; Massidda, Stefania; Botto, Barbara; Annechini, Giorgia; Spina, Michele; Re, Alessandro; Zilioli, Vittorio Ruggero; Merli, Francesco; Salvi, Flavia; Stelitano, Caterina; Bonfichi, Maurizio; Rodari, Marcello; Murru, Roberta; Magagnoli, Massimo; Anastasia, Antonella; Mazza, Rita; Giordano, Laura; Santoro, Armando

    2016-10-01

    This randomized, multicenter study evaluates the addition of bortezomib (13 mg/m(2)) to IGEV (B-IGEV) in patients with relapsed/refractory Hodgkin Lymphoma (HL). Patients received either four courses of IGEV alone (n = 40) or B-IGEV (n = 40). The primary endpoint was the complete response (CR) proportion, evaluated by FDG-PET, after induction chemotherapy. CR proportion was 39% with B-IGEV and 53% with IGEV. PFS and OS were similar between the two groups (two-year PFS: 58% vs 56%; two-year OS: 93% vs 81%). The PET-negative status after treatment was the only variable favorably influencing both PFS (two-year PFS: 77% vs 40%; p = 0.002) and OS (two-year OS: 100% vs 76%; p < 0.001). Toxicity was overall similar with the two regimens. The addition of bortezomib to IGEV does not improve response in relapsed/refractory HL patients. However, its favorable therapeutic and safety profile, and the prognostic role of pre-transplant PET negativity in patients receiving IGEV-based regimens are confirmed. PMID:26879066

  10. Impact of obesity on chemotherapy management and outcomes in women with gynecologic malignancies

    PubMed Central

    Horowitz, Neil S.; Wright, Alexi A.

    2015-01-01

    Objective To describe the effects of obesity on the pharmacokinetics and dosing of chemotherapies and provide recommendations for chemotherapy management in obese women with gynecologic malignancies. Methods PubMEd and MEDLINE databases were searched for articles published before June 2014. Only English-language articles were considered. 84 manuscripts were reviewed and 66 were included. Search terms included: obesity, overweight, body mass index, body surface area, glomerular filtration rate, chemotherapy, ovarian cancer, endometrial cancer, inflammation, and pharmacokinetics, Results Obese cancer patients have worse clinical outcomes, compared with non-obese patients. This may be because of differences in pharmacokinetics, metabolic dysregulation, or physicians' decisions to reduce chemotherapy dose-intensity during treatment to minimize toxicities. A 2012 American Society of Clinical Oncology Clinical Practice Guideline recommends using actual body weight for chemotherapy dosing in all patients treated with curative intent, irrespective of obesity, to avoid compromising clinical outcomes, including progression free survival (PFS) and overall survival (OS). In women with gynecologic cancers most studies demonstrate no difference in PFS or OS when obese patients receive the same chemotherapy dose intensity as non-obese patients, except perhaps with bevacizumab. Conclusions Chemotherapy dose-intensity is a critical determinant of cancer outcomes and should be maintained in all patients, irrespective of obesity. Future studies should prospectively examine the impact of obesity on clinical outcomes (adverse events, survival) to improve the care of this growing population of patients who are at risk for inferior clinical outcomes. PMID:25870918

  11. The significance of antral follicle size prior to stimulation in predicting ovarian response in a multiple dose GnRH antagonist protocol.

    PubMed

    Lai, Qiaohong; Chen, Cai; Zhang, Zhijun; Zhang, Shu; Yu, Qilin; Yang, Ping; Hu, Jun; Wang, Cong-Yi

    2013-01-01

    Prediction of ovarian responses prior to stimulation is not only useful for patient counseling, but also important in tailoring the optimal dosage of gonadotrophin for individual patients. By prospectively study of 214 women undergoing in vitro fertilization and embryo transfer (IVF-ET) treatment, we obtained data supporting that antral follicle size could be an additional valuable predictive marker other than the antral follicle count (AFC) in predicting ovarian response. Our studies revealed that AFC achieved the best predictive value in relation to the number of oocyte obtained, followed by antral follicle size, basal follicle stimulating hormone (FSH) and body mass index (BMI). Unlike AFC, antral follicle size was noted to be negatively correlated with the dosage (R = -0.493) and duration (R = -0.465) of rFSH stimulation. Antral follicle size was also found with higher negative regression coefficient (B = -0.661) as compared with that of basal FSH concentration (B = -0.326) and BMI (b = -0.281). More importantly, women with antral follicle size 6-7 mm showed significantly higher AFC, oocytes retrieved, fertilized oocytes and grade I/II embryos along with much lower transfer cycle cancellation rate (7.5% vs. 16-17%). Together, our data suggest that basal antral follicle size could be a valued predictive marker in women with IVF-ET treatment, in which women with antral follicle size 6-7 mm are likely predisposed to better IVF-ET outcomes. PMID:23330011

  12. Dose response and factors related to interstitial pneumonitis after bone marrow transplant

    SciTech Connect

    Sampath, Sagus; Schultheiss, Timothy E. . E-mail: schultheiss@coh.org; Wong, Jeffrey

    2005-11-01

    Purpose: Total body irradiation (TBI) and chemotherapy are common components of conditioning regimens for bone marrow transplantation. Interstitial pneumonitis (IP) is a known regimen-related complication. Using published data of IP in a multivariate logistic regression, this study sought to identify the parameters in the bone marrow transplantation conditioning regimen that were significantly associated with IP and to establish a radiation dose-response function. Methods and Materials: A retrospective review was conducted of articles that reported IP incidence along with lung dose, fractionation, dose rate, and chemotherapy regimen. In the final analysis, 20 articles (n = 1090 patients), consisting of 26 distinct TBI/chemotherapy regimens, were included in the analysis. Multivariate logistic regression was performed to determine dosimetric and chemotherapeutic factors that influenced the incidence of IP. Results: A logistic model was generated from patients receiving daily fractions of radiation. In this model, lung dose, cyclophosphamide dose, and the addition of busulfan were significantly associated with IP. An incidence of 3%-4% with chemotherapy-only conditioning regimens is estimated from the models. The {alpha}/{beta} value of the linear-quadratic model was estimated to be 2.8 Gy. The dose eliciting a 50% incidence, D {sub 50}, for IP after 120 mg/kg of cyclophosphamide was 8.8 Gy; in the absence of chemotherapy, the estimated D {sub 50} is 10.6 Gy. No dose rate effect was observed. The use of busulfan as a substitute for radiation is equivalent to treating with 14.8 Gy in 4 fractions with 50% transmission blocks shielding the lung. The logistic regression failed to find a model that adequately fit the multiple-fraction-per-day data. Conclusions: Dose responses for both lung radiation dose and cyclophosphamide dose were identified. A conditioning regimen of 12 Gy TBI in 6 daily fractions induces an IP incidence of about 11% in the absence of lung shielding

  13. [Salivation in children during anticancer chemotherapy].

    PubMed

    Popruzhenko, T V; Boris, S P

    2016-01-01

    The study aimed to assess the needs and options for salivation management in children treated with antileukemic chemotherapy. In a preliminary cross-sectional study the saliva flow rate and viscosity were evaluated in 75 leukemic children that received chemotherapy with methotrexate in low dose (44 people, 44 episode, group 1), or in high-dose (31 people, 42 episode, group 2), and in 25 healthy children (group 3). Then, 26 children were randomly divided into two groups in the 70 episodes course of high-dosed chemotherapy, and received acetylcysteine (A) or only standard oral management (S) for 1-10 day of treatment. Parameters of salivation and children performance (Lansky et al.) were evaluated. Mann-Whitney U-test was used for analysis. In group 1, 2 and 3 the flow rate (Me [LQ/HQ]) was 0.5 [0.3; 0.8]; 0.9 [0.6; 1.2] and 0.5 [0.3; 0.6] ml/min respectively (p1-3>0.05; p<0.01; p1-2<0.05). Viscosity levels in group 1, 2 and 3 were 2.75 [3.67; 3.67], 10.05 [5.3; 26.0] and 3.9 [2.7; 6.5] unites respectively (p1-3>0.05; p2, 3<0.01; p1, 2<0.01). In group A and S the flow rate was 2.7 [0.5; 4.1] and 0.4 [0.1; 2.2] ml/min (р<0.05); viscosity was 1.5 [1.2; 4.1] and 6.4 [5.3; 8.1] unites (р<0.001), performance Lansky index was 80 [65; 90] and 70 [60; 80] (р<0.01) respectively. Salivation dysfunction complicates the chemotherapy with high-dosed methotrexate in children: it is indicated by high viscosity combined with elevated flow rate. Acetylcysteine normalizes saliva viscosity and improves children's performance. PMID:27239994

  14. [Assessment of hand-foot syndrome in cancer patients treated with capecitabine-containing chemotherapy].

    PubMed

    Yamagiwa, Kouhei; Shigematsu, Tadashi; Takeda, Keiko; Shirai, Masahiro; Amemori, Keiko; Sunda, Kazumi; Koike, Chikayo; Yamada, Toshimi

    2013-12-01

    Capecitabine is one of the most effective oral chemotherapeutic drugs for advanced or recurrent colorectal cancer and gastric cancer. Capecitabine-containing chemotherapy is recommended as a first-line option for gastrointestinal tract cancer. The incidence of hand-foot syndrome (HFS), an adverse event of chemotherapy with capecitabine, is high. Moreover, once the symptoms of HFS are identified, they can significantly impair the quality of life (QOL) of patients. HFS should be managed by dose interruption and, if necessary, by dose reduction. Pharmacists and oncology nurses play an increasingly important role in the early identification and prevention of HFS through patient education and close clinical assessment. The aim of this study was to evaluate the efficacy of support tools for the early identification, prevention, and management of HFS and to assess the effectiveness of "patient self-check sheets". The patient was detected as having HFS of mild severity and had used a moisturizer at the time of initiation of therapy. Maintaining moisture retention is important in the management of HFS. The ambulatory team plays a key role by using self-check sheets to educate patients on how to recognize HFS, when to interrupt treatment, and how to adjust the dose so as to maintain effective therapy with capecitabine. For the continuation and completion of treatment and for maintaining an improved QOL in the home environment, supportive measures for adverse effects such as HFS and an ambulatory team are indispensable. PMID:24712132

  15. Attenuation effect of Abnormal Savda Munziq on liver and heart toxicity caused by chemotherapy in mice

    PubMed Central

    AIKEMU, AINIWAER; AMAT, NURMUHAMAT; YUSUP, ABDIRYIM; SHAN, LIANLIAN; QI, XINWEI; UPUR, HALMURAT

    2016-01-01

    Abnormal Savda Munziq (ASMq), an Uighur medicine formula commonly used in the treatment of cancer, has been speculated to possess antioxidative and antiproliferative effects, and to regulate immune activity. The present study was designed to systematically elucidate the toxicity-reducing activity of ASMq in mice undergoing combination chemotherapy with doxorubicin and 5-fluorouracil (5-FU). The mice were divided into normal (saline, 10 ml/kg) and doxorubicin + 5-FU groups (doxorubicin, 2.5 mg/kg; 5-FU, 10 mg/kg on alternate days). In addition, three groups received different doses of ASMq (2, 4 and 8 g/kg), in addition to doxorubicin (2.5 mg/kg) and 5-FU (10 mg/kg) treatment on alternate days. The histology of the heart and liver, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activity, malondialdehyde (MDA) concentrations in heart homogenate, and various biochemical parameters of the liver were evaluated. Compared with the normal control group, ASMq dose-dependently improved a number of variables, including body weight, liver index, transaminase and total protein, and partially normalized liver and cardiac pathology. ASMq restored activities of defense antioxidant enzymes SOD and GSH-Px towards normal levels, and decreased MDA concentration in dose-dependent manner. These results demonstrated that ASMq provides significant protection against doxorubicin + 5-FU combination induced hepatotoxicity and cardiotoxicity. Further studies are required to determine the effects of ASMq against doxorubicin + 5-FU-induced toxicity during chemotherapy in vivo. PMID:27347066

  16. Therapeutic Non-Toxic Doses of TNF Induce Significant Regression in TNFR2-p75 Knockdown Lewis Lung Carcinoma Tumor Implants

    PubMed Central

    Sasi, Sharath P.; Bae, Sanggyu; Song, Jin; Perepletchikov, Aleksandr; Schneider, Douglas; Carrozza, Joseph; Yan, Xinhua; Kishore, Raj; Enderling, Heiko; Goukassian, David A.

    2014-01-01

    Tumor necrosis factor-alpha (TNF) binds to two receptors: TNFR1/p55-cytotoxic and TNFR2/p75-pro-survival. We have shown that tumor growth in p75 knockout (KO) mice was decreased more than 2-fold in Lewis lung carcinoma (LLCs). We hypothesized that selective blocking of TNFR2/p75 LLCs may sensitize them to TNF-induced apoptosis and affect the tumor growth. We implanted intact and p75 knockdown (KD)-LLCs (>90%, using shRNA) into wild type (WT) mice flanks. On day 8 post-inoculation, recombinant murine (rm) TNF-α (12.5 ng/gr of body weight) or saline was injected twice daily for 6 days. Tumor volumes (tV) were measured daily and tumor weights (tW) on day 15, when study was terminated due to large tumors in LLC+TNF group. Tubular bones, spleens and peripheral blood (PB) were examined to determine possible TNF toxicity. There was no significant difference in tV or tW between LLC minus (-) TNF and p75KD/LLC-TNF tumors. Compared to 3 control groups, p75KD/LLC+TNF showed >2-5-fold decreases in tV (p<0.001) and tW (p<0.0001). There was no difference in tV or tW end of study vs. before injections in p75KD/LLC+TNF group. In 3 other groups tV and tW were increased 2.7-4.5-fold (p<0.01, p<0.0002 and p<0.0001). Pathological examination revealed that 1/3 of p75KD/LLC+rmTNF tumors were 100% necrotic, the remaining revealed 40-60% necrosis. No toxicity was detected in bone marrow, spleen and peripheral blood. We concluded that blocking TNFR2/p75 in LLCs combined with intra-tumoral rmTNF injections inhibit LLC tumor growth. This could represent a novel and effective therapy against lung neoplasms and a new paradigm in cancer therapeutics. PMID:24664144

  17. Pathophysiology of cardiotoxicity induced by nonanthracycline chemotherapy.

    PubMed

    Madeddu, Clelia; Deidda, Martino; Piras, Alessandra; Cadeddu, Christian; Demurtas, Laura; Puzzoni, Marco; Piscopo, Giovanna; Scartozzi, Mario; Mercuro, Giuseppe

    2016-05-01

    The risk and mechanism of chemotherapy-induced cardiotoxicity (CTX) vary depending on the type and intensity of the anticancer regimen. Myriad chemotherapeutic drugs produce adverse cardiovascular effects such as arterial hypertension, heart failure, and thromboembolic events. Among the numerous classes of these drugs, anthracyclines have been studied most extensively because of their overt cardiovascular effects and the high associated incidence of heart failure. However, CTX might also be caused by other types of chemotherapeutic agents, including alkylating agents (cyclophosphamide, ifosfamide), platinum agents, antimetabolites (5-fluorouracil, capecitabine), antibiotics (mitoxantrone, mitomycin, bleomycin), and antimicrotubule agents (taxanes). Here, we review the incidence, clinical impact, and potential mechanisms of CTX associated with nonanthracycline chemotherapy used for cancer patients. The published data support a marked increase in CTX risk, particularly with certain drugs such as 5-fluorouracil and cisplatin. Each anticancer regimen is associated with distinct modes of heart damage, both symptomatic and asymptomatic. However, the underlying mechanisms of CTX have been established only in a few cases, and only few nonanthracycline chemotherapeutics (mitoxantrone, mitomycin, ifosfamide) act through a recognizable mechanism and show a predictable dose dependence. Lastly, nonanthracycline chemotherapy can induce both chronic lesions, such as systolic dysfunction, and acute lesions, such as the ischemia that occurs within hours or days after treatment. An increased understanding of the incidence, mechanisms, and potential therapeutic targets of CTX induced by various nonanthracycline chemotherapeutic agents is clearly required. PMID:27183520

  18. [Chemotherapies of negative schizophrenia].

    PubMed

    Petit, M; Dollfus, S

    1991-01-01

    Five years ago, Goldberg claimed that negative symptoms of schizophrenia do respond to neuroleptics. This apparent discovery is, in fact, a very common way of thinking for European schools of psychiatry, specially the French one guided by Delay and Deniker. Initially focused on reserpine and some alerting phenothiazines such as thioproperazine, this opinion has been extended to benzamides in the 1970s. The analysis of the publications devoted to this point indicates that several drugs are actually considered as potent disinhibitors (i.e. active on negative symptoms of schizophrenia): Phenothiazines: As shown in the controlled studies by Itil (1971), Poirier-Littré (1988), fluphenazine and pipotiazine improve the BPRS anergia factor and the SANS score. Butyrophenones: The first description of the "imipramine like" effect of trifluperidol by Janssen (1959) initiated the studies by Gallant (1960), Fox (1963). They compared trifluperidol at low doses versus haloperidol and chlorpromazine at medium and high doses, BPRS anergia factor improved only at low doses. Diphenylbutylpiperidines (DPBP): Meltzer's review (1986) concluded to the efficacy of such drugs on negative symptoms appearing as a specific biochemical relationship effect. A definite analysis about doses leads to a very different interpretation: DPBP low doses and only low doses improved negative symptoms as much as some low doses of phenothiazines. On the opposite, DPBP, phenothiazines and butyrophenones high doses are inefficient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1683624

  19. [Chemotherapy and the heart].

    PubMed

    Plana, Juan C

    2011-05-01

    The improvements in cancer detection and therapy have created a new cohort of patients who will experience sufficient survival to develop the cardiac complications of the cancer therapy. Three-dimensional echocardiography has been validated as the ultrasound modality with the best accuracy for the calculation of ejection fraction when compared to magnetic resonance imaging, the current gold standard, making it the tool of choice, when available, for the initial evaluation and follow up of the patient receiving chemotherapy. If three-dimensional echocardiography is not available, or if the quality of the images is inadequate, the use of ultrasound contrast can be useful for the definition of the endocardial border and identification of the true apex of the heart, enhancing the ability of the interpreter to accurately calculate volumes and ejection fraction. Two-dimensional strain appears promising as a tool to identify abnormalities in myocardial mechanics very early on during cardiotoxicity, allowing the prediction of later overt systolic dysfunction. This parameter may be useful in the detection of chemotherapy treated patients who could benefit from alternate therapies, thereby decreasing the incidence of cardiotoxicity and its associated morbidity and mortality. PMID:21492985

  20. The extent of chromosomal aberrations induced by chemotherapy in non-human primates depends on the schedule of administration.

    PubMed

    Rao, V Koneti; Knutsen, Turid; Ried, Thomas; Wangsa, Darawalee; Flynn, Bernard Mike; Langham, Gregory; Egorin, Merrill J; Cole, Diane; Balis, Frank; Steinberg, Seth M; Bates, Susan; Fojo, Tito

    2005-06-01

    We utilized a non-human primate model, the rhesus monkey (Macaca mulatta), to quantitate the extent of chromosomal damage in bone marrow cells following chemotherapy. Thiotepa, etoposide, and paclitaxel were chosen as the chemotherapy agents due to their distinct mechanisms of action. Chromosomal aberrations were quantitated using traditional Giemsa stain. We sought to evaluate the extent to which genotoxicity was dependent on the schedule of administration by giving chemotherapy as either a bolus or a 96 h continuous infusion. Neutropenia and areas under the concentration curve (AUCs) were monitored to ensure comparable cytotoxicity and dose administered. At least 100 metaphases were scored in each marrow sample by an investigator unaware of the treatment history of the animals. All three drugs produced a statistically significant higher percentage of abnormal metaphases following bolus chemotherapy (p<0.0001, p=0.0015 and p<0.0001 for thiotepa, etoposide and paclitaxel, respectively). We conclude that infusional administration of thiotepa, etoposide and paclitaxel is less genotoxic to normal bone marrow cells than is bolus administration. These results suggest infusional regimens may be considered where there are concerns about long-term genotoxic sequelae, including secondary cancer, teratogenicity, or possibly the development of drug resistance. We believe this approach provides a reproducible model in which drugs and eventually, regimens can be compared. PMID:15927870

  1. Pre-irradiation with low-dose 12C6+ beam significantly enhances the efficacy of AdCMV-p53 gene therapy in human non-small lung cancer

    NASA Astrophysics Data System (ADS)

    Liu, Bing; Zhang, Hong; Li, Wenjian; Li, Qiang; Zhou, Guangming; Xie, Yi; Hao, Jifang; Min, Fengling; Zhou, Qingming; Duan, Xin

    2007-04-01

    The combination of ionizing radiation and gene therapy has been investigated. However, there are very few reports about the combination of heavy-ion irradiation and gene therapy. To determine if the pre-exposure to low-dose heavy ion beam enhances the suppression of AdCMV-p53 on non-small lung cancer (NSLC), the cells pre-irradiated or non-irradiated were infected with 20, 40 MOI of AdCMV-p53. Survival fraction and the relative biology effect (RBE) were determined by clonogenic assay. The results showed that the proportions of p53 positive cells in 12C6+ beam induced AdCMV-p53 infected cells were more than 90%, which were significantly more than those in γ-ray induced AdCMV-p53 infected cells. The pre-exposure to low-dose 12C6+ beam significantly prevented the G0/G1 arrest and activated G2/M checkpoints. The pre-exposure to 12C6+ beam significantly improved cell to apoptosis. RBEs for the 12C6+ + AdCMV-p53 infection groups were 30% 60%, 20% 130% and 30% 70% more than those for the 12C6+-irradiated only, AdCMV-p53 infected only, and γ-irradiation induced AdCMVp53 infected groups, respectively. The data suggested that the pre-exposure to low-dose 12C6+ beam significantly promotes exogenous p53 expression in NSLC, and the suppression of AdCMV-p53 gene therapy on NSLC.

  2. Metronomic Chemotherapy for Metastatic Breast Cancer – a Systematic Review of the Literature

    PubMed Central

    Banys-Paluchowski, M.; Schütz, F.; Ruckhäberle, E.; Krawczyk, N.; Fehm, T.

    2016-01-01

    Conventional chemotherapy is generally administered in high doses followed by a treatment-free period to give the body needful time to recover. This “maximum tolerated dose” approach results in high response rates. However, long periods between therapy cycles can lead to development of resistance mechanisms and consequently disease progression. One of the most interesting alternative strategies is metronomic chemotherapy. This concept relies on the continuous administration of chemotherapy at low doses and aims at targeting endothelial cells in the tumor bed as well. Recently, metronomic chemotherapy has been incorporated into the recommendations issued by the German AGO expert panel (www.ago-online.de). A systematic review of PubMed/Medline, ClinicalTrials.gov, the European Clinical Trials Database (EudraCT) and the Cochrane Database was conducted. In the present review, we discuss the current evidence on metronomic chemotherapy in metastatic breast cancer. PMID:27239061

  3. Neoadjuvant chemotherapy for radioinduced osteosarcoma of the extremity: The Rizzoli experience in 20 cases

    SciTech Connect

    Bacci, Gaetano . E-mail: gaetano.bacci@ior.it; Longhi, Alessandra; Forni, Cristiana R.N.; Fabbri, Nicola; Briccoli, Antonio; Barbieri, Enza; Mercuri, Mario; Balladelli, Alba B.A.; Ferrari, Stefano; Picci, Piero

    2007-02-01

    Purpose: Evaluate treatment and outcome of 20 patients with radioinduced osteosarcoma (RIO). Because of previous primary tumor treatment, RIO protocols were different from others we used for non-RIO. Patients and Methods: Between 1983 and 1998, we treated 20 RIO patients, ages 4-36 years (mean 16 years), with chemotherapy (two cycles before surgery, three postoperatively). The first preoperative cycle consisted of high-dose Methotrexate (HDMTX)/Cisplatinum (CDP)/Adriamycin (ADM) and the second of HDMTX/CDP/Ifosfamide (IFO). The three postoperative treatments were performed with cycles of MTX/CDP; IFO was used as single agent per cycle repeated three times. Results: Two patients received palliative treatment because their osteosarcoma remained unresectable after preoperative chemotherapy. The remaining 18 patients had surgery (7 amputations, 11 resections); histologic response to preoperative chemotherapy was good in 8 patients, poor in 10. At a mean follow-up of 11 years (range, 7-22 years), 9 patients remained continuously disease-free, 10 died from osteosarcoma and 1 died from a third neoplasm (myeloid acute leukemia). These results are not significantly different from those achieved in 754 patients with conventional osteosarcoma treated in the same period with protocols used for conventional treatment. However, this later group had an 18% 3-year event-free survival after treatment of relapse vs. 0% in the RIO group. Conclusion: Treated with neoadjuvant chemotherapy RIO seem to have an outcome that is not significantly different from that of comparable patients with conventional primary high grade osteosarcoma (5-year event-free survival: 40% vs. 60%, p = NS; 5-year overall survival 40% vs. 67%, p < 0.00008.

  4. Structural Brain Alterations in Children an Average of 5 Years after Surgery and Chemotherapy for Brain Tumors

    PubMed Central

    Nelson, Mary Baron; Macey, Paul M.; Harper, Ronald M.; Jacob, Eufemia; Patel, Sunita K.; Finlay, Jonathan L.; Nelson, Marvin D.; Compton, Peggy

    2014-01-01

    Background Young children with brain tumors are often treated with high-dose chemotherapy after surgery to avoid brain tissue injury associated with irradiation. The effects of systemic chemotherapy on healthy brain tissue in this population, however, are unclear. Our objective was to compare gray and white matter integrity using MRI procedures in children with brain tumors (n=7, mean age 8.3 years), treated with surgery and high-dose chemotherapy followed by autologous hematopoietic cell rescue (AuHCR) an average of 5.4 years earlier, to age- and gender-matched healthy controls (n=9, mean age 9.3 years). Methods Diffusion tensor imaging data were collected to evaluate tissue integrity throughout the brain, as measured by mean diffusivity (MD), a marker of glial, neuronal, and axonal status, and fractional anisotropy (FA), an index of axonal health. Individual MD and FA maps were calculated, normalized, smoothed, and compared between groups using analysis of covariance, with age and sex as covariates. Results Higher mean diffusivity values, indicative of injury, emerged in patients compared with controls (p<0.05, corrected for multiple comparisons), and were especially apparent in the central thalamus, external capsule, putamen, globus pallidus and pons. Reduced FA values in some regions did not reach significance after correction for multiple comparisons. Conclusions Children treated with surgery and high-dose chemotherapy with AuHCR for brain tumors an average of 5.4 years earlier show alterations in white and gray matter in multiple brain areas distant from the tumor site, raising the possibility for long-term consequences of the tumor or treatment. PMID:24830985

  5. Drug scheduling of cancer chemotherapy based on natural actor-critic approach.

    PubMed

    Ahn, Inkyung; Park, Jooyoung

    2011-11-01

    Recently, reinforcement learning methods have drawn significant interests in the area of artificial intelligence, and have been successfully applied to various decision-making problems. In this paper, we study the applicability of the NAC (natural actor-critic) approach, a state-of-the-art reinforcement learning method, to the drug scheduling of cancer chemotherapy for an ODE (ordinary differential equation)-based tumor growth model. ODE-based cancer dynamics modeling is an active research area, and many different mathematical models have been proposed. Among these, we use the model proposed by de Pillis and Radunskaya (2003), which considers the growth of tumor cells and their interaction with normal cells and immune cells. The NAC approach is applied to this ODE model with the goal of minimizing the tumor cell population and the drug amount while maintaining the adequate population levels of normal cells and immune cells. In the framework of the NAC approach, the drug dose is regarded as the control input, and the reward signal is defined as a function of the control input and the cell populations of tumor cells, normal cells, and immune cells. According to the control policy found by the NAC approach, effective drug scheduling in cancer chemotherapy for the considered scenarios has turned out to be close to the strategy of continuing drug injection from the beginning until an appropriate time. Also, simulation results showed that the NAC approach can yield better performance than conventional pulsed chemotherapy. PMID:21839140

  6. In situ injection of phenylboronic acid based low molecular weight gels for efficient chemotherapy.

    PubMed

    Gao, Wenxia; Liang, Yan; Peng, Xinyu; Hu, Yalong; Zhang, Longgui; Wu, Huayue; He, Bin

    2016-10-01

    Injectable low molecular weight gels (LMWGs) based on the derivatives of phenylboronic acid were prepared and used as substrates for efficient in situ chemotherapy. The gelators as well as LMWGs were characterized by (1)H NMR, UV-vis, FTIR, MS and SEM. Anticancer drug doxorubicin hydrochloride (DOX) was encapsulated in the gels. The rheological properties and rapid recovery capability of both blank and drug-loaded gels were tested. The LMWGs were non-toxic to both 3T3 fibroblasts and 4T1 breast cancer cells. The gels were formed rapidly after injected in vivo. The in vivo anticancer activities of DOX-loaded LMWGs were investigated in breast cancer bearing mice. The intratumoral injection of DOX loaded LMWGs with dose of 30 mg/kg revealed that the gels could coat around the tumor tissues to release DOX sustainingly and maintain effective DOX concentration for chemotherapy. The systemic toxicity of DOX was reduced significantly with the in situ administration of LMWGs formulations. The injectable LMWGs exhibited excellent therapeutic efficacy and low side effects in local chemotherapy. PMID:27497056

  7. Equivalent chemotherapy efficacy against leukemia in mice treated with topical vasoconstrictors to prevent cancer therapy side effects.

    PubMed

    Graul-Conroy, Amanda; Hicks, Emily J; Fahl, William E

    2016-06-15

    Topically applied vasoconstrictor is a new strategy to prevent oral mucositis and alopecia, two complications of chemotherapy and stem-cell transplant. We sought to determine whether mice treated with topical vasoconstrictor minutes before chemotherapy to suppress L1210 leukemia would develop a vasoconstrictor-induced L1210 cell sanctuary, and with it, significantly worse survival outcomes. B6D2F1 mice received 10(4) mouse L1210 leukemia cells via retro-orbital intravenous injection and were then divided into treatment groups, which included: (i) no further treatment, (ii) a single, sub-curative, intraperitoneal dose of cyclophosphamide (90 µg/gm bw) 24 hr after L1210 cell inoculation, (iii) topical epinephrine (25-400 mM) to clipped dorsal backs 20 min before cyclophosphamide or (iv) orotopical phenylephrine (16-130 mM), epinephrine (10 mM) or norepinephrine (25 mM) 20 min before cyclophosphamide. All mice were then followed until day of death. Differences in median survival time and percent survival between mice receiving cyclophosphamide alone and mice treated with either orotopical phenylephrine, epinephrine or norepinephrine; or topical epinephrine before cyclophosphamide were not significantly different. A discernible leukemia sanctuary was not created by topical vasoconstrictor treatment prior to chemotherapy; there was no significant difference in leukemia progression between untreated mice and those treated with either orotopical or topical vasoconstrictor before chemotherapy. We have opened a Phase I/IIa dose escalation trial to evaluate the safety and efficacy of orotopical phenylephrine in preventing oral mucositis in subjects undergoing hematopoietic stem cell transplant conditioning with cyclophosphamide plus total body irradiation. This could provide a cost-effective and convenient method to prevent oral mucositis. PMID:26860340

  8. Improved Tumor-Specific Drug Accumulation by Polymer Therapeutics with pH-Sensitive Drug Release Overcomes Chemotherapy Resistance.

    PubMed

    Heinrich, Anne-Kathrin; Lucas, Henrike; Schindler, Lucie; Chytil, Petr; Etrych, Tomáš; Mäder, Karsten; Mueller, Thomas

    2016-05-01

    The success of chemotherapy is limited by poor selectivity of active drugs combined with occurrence of tumor resistance. New star-like structured N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-based drug delivery systems containing doxorubicin attached via a pH-sensitive hydrazone bond were designed and investigated for their ability to overcome chemotherapy resistance. These conjugates combine two strategies to achieve a high drug concentration selectively at the tumor site: (I) high accumulation by passive tumor targeting based on enhanced permeability and retention effect and (II) pH-sensitive site-specific drug release due to an acidic tumor microenvironment. Mice bearing doxorubicin-resistant xenograft tumors were treated with doxorubicin, PBS, poly HPMA (pHPMA) precursor or pHPMA-doxorubicin conjugate at different equivalent doses of 5 mg/kg bodyweight doxorubicin up to a 7-fold total dose using different treatment schedules. Intratumoral drug accumulation was analyzed by fluorescence imaging utilizing intrinsic fluorescence of doxorubicin. Free doxorubicin induced significant toxicity but hardly any tumor-inhibiting effects. Administering at least a 3-fold dose of pHPMA-doxorubicin conjugate was necessary to induce a transient response, whereas doses of about 5- to 6-fold induced strong regressions. Tumors completely disappeared in some cases. The onset of response was differential delayed depending on the tumor model, which could be ascribed to distinct characteristics of the microenvironment. Further fluorescence imaging-based analyses regarding underlying mechanisms of the delayed response revealed a related switch to a more supporting intratumoral microenvironment for effective drug release. In conclusion, the current study demonstrates that the concept of tumor site-restricted high-dose chemotherapy is able to overcome therapy resistance. Mol Cancer Ther; 15(5); 998-1007. ©2016 AACR. PMID:26939698

  9. Chemotherapy targeting cancer stem cells

    PubMed Central

    Liu, Haiguang; Lv, Lin; Yang, Kai

    2015-01-01

    Conventional chemotherapy is the main treatment for cancer and benefits patients in the form of decreased relapse and metastasis and longer overall survival. However, as the target therapy drugs and delivery systems are not wholly precise, it also results in quite a few side effects, and is less efficient in many cancers due to the spared cancer stem cells, which are considered the reason for chemotherapy resistance, relapse, and metastasis. Conventional chemotherapy limitations and the cancer stem cell hypothesis inspired our search for a novel chemotherapy targeting cancer stem cells. In this review, we summarize cancer stem cell enrichment methods, the search for new efficient drugs, and the delivery of drugs targeting cancer stem cells. We also discuss cancer stem cell hierarchy complexity and the corresponding combination therapy for both cancer stem and non-stem cells. Learning from cancer stem cells may reveal novel strategies for chemotherapy in the future. PMID:26045975

  10. Pharmacokinetics, safety, and efficacy of APF530 (extended-release granisetron) in patients receiving moderately or highly emetogenic chemotherapy: results of two Phase II trials

    PubMed Central

    Gabrail, Nashat; Yanagihara, Ronald; Spaczyński, Marek; Cooper, William; O’Boyle, Erin; Smith, Carrie; Boccia, Ralph

    2015-01-01

    Background Despite advances with new therapies, a significant proportion of patients (>30%) suffer delayed-onset chemotherapy-induced nausea and vomiting (CINV) despite use of antiemetics. APF530 is a sustained-release subcutaneous (SC) formulation of granisetron for preventing CINV. APF530 pharmacokinetics, safety, and efficacy were studied in two open-label, single-dose Phase II trials (C2005-01 and C2007-01, respectively) in patients receiving moderately emetogenic chemotherapy or highly emetogenic chemotherapy. Methods In C2005-01, 45 patients received APF530 250, 500, or 750 mg SC (granisetron 5, 10, or 15 mg, respectively). In C2007-01, 35 patients were randomized to APF530 250 or 500 mg SC. Injections were given 30 to 60 minutes before single-day moderately emetogenic chemotherapy or highly emetogenic chemotherapy. Plasma granisetron was measured from predose to 168 hours after study drug administration. Safety and efficacy were also evaluated. Results APF530 pharmacokinetics were dose proportional, with slow absorption and elimination of granisetron after a single SC dose. Median time to maximum plasma concentration and half-life were similar for APF530 250 and 500 mg in both trials, with no differences between the groups receiving moderately and highly emetogenic chemotherapy. Exposure to granisetron was maintained at a therapeutic level over the delayed-onset phase, at least 168 hours. Adverse events in both trials were as expected for granisetron; injection site reactions (eg, erythema and induration) were predominantly mild and seen in ≤20% of patients. Complete responses (no emesis, with no rescue medication) were obtained in the acute, delayed, and overall phases in ≥80% and ≥75% of patients in both trials with the 250 and 500 mg doses, respectively. Conclusion After a single injection of APF530, there were dose-proportional pharmacokinetics and sustained concentrations of granisetron over 168 hours. The 250 and 500 mg doses were well tolerated

  11. Xanthogranulomatous Appendicitis Mimicking Residual Burkitt's Lymphoma After Chemotherapy

    PubMed Central

    Nam, Soomin; Choi, Sung-Eun; Kim, Yu Ri; Baik, Seung Hyuk; Sohn, Seung-Kook

    2016-01-01

    The case of a 23-year-old female treated with aggressive high-dose therapy for Burkitt's lymphoma is reported. A positron emission tomography and computed tomography scan after completion of chemotherapy revealed a residual hypermetabolic lesion in the right pelvic cavity. A pelvic magnetic resonance imaging scan showed circumferential wall thickening at the tip of the appendix. A laparoscopic exploration and appendectomy were performed, and a pathologic examination of the resected appendix revealed xanthogranulomatous appendicitis. This is a rare case of a xanthogranulomatous appendicitis mimicking remnant Burkitt's lymphoma after completion of chemotherapy. PMID:27218100

  12. Xanthogranulomatous Appendicitis Mimicking Residual Burkitt's Lymphoma After Chemotherapy.

    PubMed

    Nam, Soomin; Kang, Jeonghyun; Choi, Sung-Eun; Kim, Yu Ri; Baik, Seung Hyuk; Sohn, Seung-Kook

    2016-04-01

    The case of a 23-year-old female treated with aggressive high-dose therapy for Burkitt's lymphoma is reported. A positron emission tomography and computed tomography scan after completion of chemotherapy revealed a residual hypermetabolic lesion in the right pelvic cavity. A pelvic magnetic resonance imaging scan showed circumferential wall thickening at the tip of the appendix. A laparoscopic exploration and appendectomy were performed, and a pathologic examination of the resected appendix revealed xanthogranulomatous appendicitis. This is a rare case of a xanthogranulomatous appendicitis mimicking remnant Burkitt's lymphoma after completion of chemotherapy. PMID:27218100

  13. Pioneers in Antimicrobial Chemotherapy.

    PubMed

    Gupta, Neha; Rodrigues, Camilla; Soman, Rajeev

    2015-09-01

    "If we are not careful, we soon will be in the post-antibiotic era, and for some patients and some microbes we are already there"- Tom Friedan Antibiotics revolutionized medicine in the 20th century. The era of antibacterial chemotherapy began in 1907 with the discovery of arsphenamine, first synthesized by Alferd Bertheim and Paul Ehrlich in 1907, used to treat syphilis. The first systemically active antibiotic, Prontosil was discovered in 1933 by Gerhard Domagk, for which he was awarded the 1939 Nobel Prize. Fleming's accidental discovery and isolation of penicillin in September 1928 marked the start of modern antibiotics. It was a discovery that changed the course of history and saved millions of lives. PMID:27608881

  14. Early injury to cortical and cancellous bone from induction chemotherapy for adolescents and young adults treated for acute lymphoblastic leukemia.

    PubMed

    Orgel, E; Mueske, N M; Wren, T A L; Gilsanz, V; Butturini, A M; Freyer, D R; Mittelman, S D

    2016-04-01

    Diminished bone density and skeletal fractures are common morbidities during and following therapy for acute lymphoblastic leukemia (ALL). While cumulative doses of osteotoxic chemotherapy for ALL have been reported to adversely impact bone density, the timing of onset of this effect as well as other changes to bone structure is not well characterized. We therefore conducted a prospective cohort study in pre-adolescent and adolescent patients (10-21years) newly diagnosed with ALL (n=38) to explore leukemia-related changes to bone at diagnosis and the subsequent impact of the first phase of chemotherapy ("Induction"). Using quantitative computerized tomography (QCT), we found that pre-chemotherapy bone properties were similar to age- and sex-matched controls. Subsequently over the one month Induction period, however, cancellous volumetric bone mineral density (vBMD) decreased markedly (-26.8%, p<0.001) with sparing of cortical vBMD (tibia -0.0%, p=0.860, femur -0.7%, p=0.290). The tibia underwent significant cortical thinning (average cortical thickness-1.2%, p<0.001; cortical area-0.4%, p=0.014), while the femur was less affected. Areal BMD (aBMD) concurrently measured by dual-energy X-ray absorptiometry (DXA) underestimated changes from baseline as compared to vBMD. Biochemical evidence revealed prevalent Vitamin D insufficiency and a net resorptive state at start and end of Induction. Our findings demonstrate for the first time that significant alterations to cancellous and cortical bone develop during the first month of treatment, far earlier during ALL therapy than previously considered. Given that osteotoxic chemotherapy is integral to curative regimens for ALL, these results provide reason to re-evaluate traditional approaches toward chemotherapy-associated bone toxicity and highlight the urgent need for investigation into interventions to mitigate this common adverse effect. PMID:26851412

  15. Intraoperative imaging identifies thymoma margins following neoadjuvant chemotherapy

    PubMed Central

    Keating, Jane J.; Nims, Sarah; Venegas, Ollin; Jiang, Jack; Holt, David; Kucharczuk, John C.; Deshpande, Charuhas; Singhal, Sunil

    2016-01-01

    Near infrared (NIR) molecular imaging is useful to identify tumor margins during surgery; however, the value of this technology has not been evaluated for tumors that have been pre-treated with chemotherapy. We hypothesized that NIR molecular imaging could locate mediastinal tumor margins in a murine model after neoadjuvant chemotherapy. Flank thymomas were established on mice. Two separate experiments were performed for tumor margin detection. The first experiment compared (i) surgery and (ii) surgery + NIR imaging. The second experiment compared (iii) preoperative chemotherapy + surgery, and (iv) preoperative chemotherapy + surgery + NIR imaging. NIR imaging occurred following systemic injection of indocyanine green. Margins were assessed for residual tumor cells by pathology. NIR imaging was superior at detecting retained tumor cells during surgery compared to standard techniques (surgery alone vs. surgery + NIR imaging, 20% vs. 80%, respectively). Following chemotherapy, the sensitivity of NIR imaging of tumor margins was not significantly altered. The mean in vivo tumor-to-background fluorescence ratio was similar in the treatment-naïve and chemotherapy groups ((p = 0.899): 3.79 ± 0.69 (IQR 3.29 - 4.25) vs. 3.79 ± 0.52 (IQR 3.40 – 4.03)). We conclude that chemotherapy does not affect tumor fluorescence or identification of retained cancer cells at margins. PMID:26689990

  16. Intraoperative imaging identifies thymoma margins following neoadjuvant chemotherapy.

    PubMed

    Keating, Jane J; Nims, Sarah; Venegas, Ollin; Jiang, Jack; Holt, David; Kucharczuk, John C; Deshpande, Charuhas; Singhal, Sunil

    2016-01-19

    Near infrared (NIR) molecular imaging is useful to identify tumor margins during surgery; however, the value of this technology has not been evaluated for tumors that have been pre-treated with chemotherapy. We hypothesized that NIR molecular imaging could locate mediastinal tumor margins in a murine model after neoadjuvant chemotherapy. Flank thymomas were established on mice. Two separate experiments were performed for tumor margin detection. The first experiment compared (i) surgery and (ii) surgery + NIR imaging. The second experiment compared (iii) preoperative chemotherapy + surgery, and (iv) preoperative chemotherapy + surgery + NIR imaging. NIR imaging occurred following systemic injection of indocyanine green. Margins were assessed for residual tumor cells by pathology. NIR imaging was superior at detecting retained tumor cells during surgery compared to standard techniques (surgery alone vs. surgery + NIR imaging, 20% vs. 80%, respectively). Following chemotherapy, the sensitivity of NIR imaging of tumor margins was not significantly altered. The mean in vivo tumor-to-background fluorescence ratio was similar in the treatment-naïve and chemotherapy groups ((p = 0.899): 3.79 ± 0.69 (IQR 3.29 - 4.25) vs. 3.79 ± 0.52 (IQR 3.40 - 4.03)). We conclude that chemotherapy does not affect tumor fluorescence or identification of retained cancer cells at margins. PMID:26689990

  17. Chemotherapy and prognosis in advanced thymic carcinoma patients

    PubMed Central

    Song, Zhengbo; Yu, Xinmin; Zhang, Yiping

    2015-01-01

    OBJECTIVE: The role of chemotherapy in treating advanced thymic carcinoma is unclear. The purpose of the current study was to investigate the efficacy of chemotherapy and the prognostic factors for patients with advanced thymic carcinoma. METHODS: A retrospective review of the medical records of 86 patients treated with chemotherapy for advanced thymic carcinoma was conducted between 2000 and 2012 at our institution. The clinical characteristics, chemotherapy regimens and prognostic factors were analyzed. Survival curves were plotted using the Kaplan–Meier method and the Cox proportional hazard model was used for multivariate analysis. RESULTS: Of the 86 patients, 56 were male and 30 were female. The median survival time was 24.5 months. For the first-line chemotherapy treatment, the objective response rate was 47.7% and the disease control rate was 80.2%. The median progression-free survival for all patients was 6.5 months for first-line chemotherapy. No significant differences in progression-free survival were observed among the different chemotherapy regimens. Multivariate analyses revealed that the prognostic factors for overall survival included performance status (p=0.043), histology grade (p=0.048), and liver metastasis (p=0.047). CONCLUSION: Our results suggest that there is no difference in efficacy between multiagent and doublet regimens. The prognosis of patients with advanced thymic carcinoma can be predicted based on histological grade, liver metastasis and performance status. PMID:26735216

  18. Altered discharges of spinal neurons parallel the behavioral phenotype shown by rats with bortezomib related chemotherapy induced peripheral neuropathy

    PubMed Central

    Robinson, Caleb R.; Zhang, Hongmei; Dougherty, Patrick M.

    2014-01-01

    Bortezomib is a first generation proteasome inhibitor that is the frontline chemotherapy for multiple myeloma with the chief dose-limiting side effect of painful peripheral neuropathy. The goal of this study was to define the behavioral phenotype in a preclinical model of bortezomib chemotherapy-induced peripheral neuropathy (CIPN) and to test whether this is matched by changes in the physiological responses of spinal wide dynamic range neurons. Sprague-Dawley rats were treated with four injections of bortezomib at four doses, 0.05mg/kg, 0.10 mg/kg, 0.15 mg/kg, 0.20 mg/kg, or equal volume of saline. All doses of bortezomib above 0.05mg/kg produced showed significant dose-dependent mechanical hyperalgesia that was fully established at 30 days after treatment and that recovered to baseline levels by day 69 after treatment. Thermal, cold, and motor testing were all unaffected by treatment with bortezomib. Spinal wide dynamic range (WDR) neurons in rats with confirmed bortzomib-related CIPN showed an increase in number of evoked discharges to mechanical stimuli and exaggerated after-discharges in rats with bortezomib CIPN. PMID:24949562

  19. Understanding Resistance to Combination Chemotherapy

    PubMed Central

    Pritchard, Justin R.; Lauffenburger, Douglas A.; Hemann, Michael T.

    2014-01-01

    Summary The current clinical application of combination chemotherapy is guided by a historically successful set of practices that were developed by basic and clinical researchers 50-60 years ago. Thus, in order to understand how emerging approaches to drug development might aid the creation of new therapeutic combinations, it is critical to understand the defining principles underlying classic combination therapy and the original experimental rationales behind them. One such principle is that the use of combination therapies with independent mechanisms of action can minimize the evolution of drug resistance. Another is that in order to kill sufficient cancer cells to cure a patient, multiple drugs must be delivered at their maximum tolerated dose – a condition that allows for enhanced cancer cell killing with manageable toxicity. In light of these models, we aim to explore recent genomic evidence underlying the mechanisms of resistance to the combination regimens constructed on these principles. Interestingly, we find that emerging genomic evidence contradicts some of the rationales of early practitioners in developing commonly used drug regimens. However, we also find that the addition of recent targeted therapies has yet to change the current principles underlying the construction of anti-cancer combinatorial regimens, nor have they made substantial inroads into the treatment of most cancers. We suggest that emerging systems/network biology approaches have an immense opportunity to impact the rational development of successful drug regimens. Specifically, by examining drug combinations in multivariate ways, next generation combination therapies can be constructed with a clear understanding of how mechanisms of resistance to multi-drug regimens differ from single agent resistance. PMID:23164555

  20. Pharmacokinetics, dynamics and toxicity of docetaxel: Why the Japanese dose differs from the Western dose

    PubMed Central

    Kenmotsu, Hirotsugu; Tanigawara, Yusuke

    2015-01-01

    Docetaxel (Taxotere®) has been one of the most important chemotherapeutic drugs for cancer treatment since 1996. Although a large number of clinical studies have been conducted in various cancer fields, there is a discrepancy in the standard dose between Japan and Western countries. This article reviews the pharmacokinetic, pharmacodynamic and toxicological profiles of docetaxel, and explains why there exists an ethnic difference in dose, and further discusses which direction we should go forward to solve this problem. The original recommended dose was 100 mg/m2 every 3 weeks in US and European populations, while a Japanese phase I study suggested the recommended dose as 60 mg/m2 every 3 weeks. A prospective population pharmacokinetic analysis of docetaxel conducted in both the USA/Europe and Japan, indicated an absence of ethnic difference in the pharmacokinetics. Both analyses demonstrated that docetaxel clearance is related to α1-acid glycoprotein level, hepatic function, age and body surface area. The relationship was observed between increasing docetaxel dose and increased tumor response rates across the dose range of 60 to 100 mg/m2. The area under the serum concentration time curve (AUC) of docetaxel at the first cycle was significantly related to time to progression. Hematological toxicities were well correlated with the AUC of docetaxel, and severe hematological toxicities were more frequently observed in Japanese patients treated with 60 mg/m2, compared to the US/European patients treated with 75–100 mg/m2 dose. The Japanese population seems more susceptible to the toxicity of docetaxel. A docetaxel dose of 75 mg/m2 is now standard not only in global trials but also in recent Japanese trials. Although the optimal dose of docetaxel is still unclear, we need to continue to seek the appropriate dose of docetaxel depending on patient status and the goals of chemotherapy. PMID:25728850

  1. Toward successful migration to computerized physician order entry for chemotherapy

    PubMed Central

    Jeon, J.; Taneva, S.; Kukreti, V.; Trbovich, P.; Easty, A.C.; Rossos, P.G.; Cafazzo, J.A.

    2014-01-01

    Background Computerized physician order entry (cpoe) systems allow for medical order management in a clinical setting. Use of a cpoe has been shown to significantly improve chemotherapy safety by reducing the number of prescribing errors. Usability of these systems has been identified as a critical factor in their successful adoption. However, there is a paucity of literature investigating the usability of cpoe for chemotherapy and describing the experiences of cancer care providers in implementing and using a cpoe system. Methods A mixed-methods study, including a national survey and a workshop, was conducted to determine the current status of cpoe adoption in Canadian oncology institutions, to identify and prioritize knowledge gaps in cpoe usability and adoption, and to establish a research agenda to bridge those gaps. Survey respondents were representatives of cancer care providers from each Canadian province. The workshop participants were oncology clinicians, human factors engineers, patient safety researchers, policymakers, and hospital administrators from across Canada, with participation from the United States. Results A variety of issues related to implementing and using a cpoe for chemotherapy were identified. The major issues concerned the need for better understanding of current practices of chemotherapy ordering, preparation, and administration; a lack of system selection and procurement guidance; a lack of implementation and maintenance guidance; poor cpoe usability and workflow support; and other cpoe system design issues. An additional three research themes for addressing the existing challenges and advancing successful adoption of cpoe for chemotherapy were identified: The need to investigate variances in workflows and practices in chemotherapy ordering and administrationThe need to develop best-practice cpoe procurement and implementation guidance specifically for chemotherapyThe need to measure the effects of cpoe implementation in medical

  2. Efficacy of upfront high-dose chemotherapy plus rituximab followed by autologous peripheral blood stem cell transplantation for untreated high-intermediate-, and high-risk diffuse large B-cell lymphoma: a multicenter prospective phase II study (JSCT-NHL04).

    PubMed

    Murayama, Tohru; Fukuda, Takahiro; Okumura, Hirokazu; Sunami, Kazutaka; Sawazaki, Aiko; Maeda, Yoshinobu; Tsurumi, Hisashi; Uike, Naokuni; Hidaka, Tomonori; Takatsuka, Yoshifusa; Eto, Tetsuya; Tsuda, Hiroyuki; Fujisaki, Tomoaki; Miyamoto, Toshihiro; Tsuneyoshi, Naoko; Iyama, Satoshi; Nagafuji, Koji; Harada, Mine

    2016-06-01

    To evaluate the efficacy and feasibility of upfront high-dose chemotherapy (HDCT) and rituximab (R) followed by autologous peripheral blood stem cell transplantation (auto-PBSCT) in patients with newly diagnosed high-intermediate(HI)-, and high(H)-risk diffuse large B-cell lymphoma (DLBCL), we conducted a multicenter prospective phase II trial. In 15-60-year-old patients with H- or HI-risk DLBCL, after three courses of (R-)CHOP14, high-dose etoposide was given prior to peripheral blood stem cell harvesting. After an additional three courses of (R-)CHOP14, auto-PBSCT was performed following HDCT. The primary endpoint of the study is progression-free survival (PFS) at 2 years after registration in eligible patients. The expected PFS and the threshold PFS were estimated to be 70 and 50 %, respectively. Among 40 eligible patients registered, 30 patients completed treatment. With a median observation period in surviving eligible patients of 63 months, the 2- and 4-year PFS after registration were 79.9 and 72.0 %, respectively. The 2- and 4-year overall survival (OS) were 92.5 and 84.6 %, respectively. In 30 patients who completed treatment, the 4-year PFS and OS after auto-PBSCT were 79.2 and 85.9 %, respectively. In conclusion, the results of our study suggest that upfront HDCT and auto-PBSCT combined with rituximab is highly effective as an initial treatment for HI-, and H-risk DLBCL. PMID:27084252

  3. Chemotherapy-Induced Amenorrhea – An Update

    PubMed Central

    Liedtke, C.; Kiesel, L.

    2012-01-01

    Because of the heterogeneity in the definition of chemotherapy-induced amenorrhea (CIA) there are distinct differences in the literature with regard to its incidence as well as its dependence on various influencing factors. The occurrence of CIA varies greatly depending on the applied chemotherapy. The pathogenesis of CIA is especially based on a reduction of ovarian reserves. Various sonographic and biochemical factors can be used to exclude or confirm CIA. This is particularly important when an endocrine therapy with tamoxifen is not possible and the use of aromatase inhibitors is under consideration. CIA and especially the frequently thereby resulting early menopause can lead to pronounced restrictions in the quality of life of the affected patients, not least due to the resulting infertility. On the other hand, various studies have shown that CIA may have a positive prognostic significance. Thus, the identification of measures to prevent CIA (for example, through the use of GnRH analogues) is of particular importance. PMID:26640289

  4. Assessment of the Radiation-Equivalent of Chemotherapy Contributions in 1-Phase Radio-chemotherapy Treatment of Muscle-Invasive Bladder Cancer

    SciTech Connect

    Plataniotis, George A.; Dale, Roger G.

    2014-03-15

    Purpose: To estimate the radiation equivalent of the chemotherapy contribution to observed complete response rates in published results of 1-phase radio-chemotherapy of muscle-invasive bladder cancer. Methods and Materials: A standard logistic dose–response curve was fitted to data from radiation therapy-alone trials and then used as the platform from which to quantify the chemotherapy contribution in 1-phase radio-chemotherapy trials. Two possible mechanisms of chemotherapy effect were assumed (1) a fixed radiation-independent contribution to local control; or (2) a fixed degree of chemotherapy-induced radiosensitization. A combination of both mechanisms was also considered. Results: The respective best-fit values of the independent chemotherapy-induced complete response (CCR) and radiosensitization (s) coefficients were 0.40 (95% confidence interval −0.07 to 0.87) and 1.30 (95% confidence interval 0.86-1.70). Independent chemotherapy effect was slightly favored by the analysis, and the derived CCR value was consistent with reports of pathologic complete response rates seen in neoadjuvant chemotherapy-alone treatments of muscle-invasive bladder cancer. The radiation equivalent of the CCR was 36.3 Gy. Conclusion: Although the data points in the analyzed radio-chemotherapy studies are widely dispersed (largely on account of the diverse range of chemotherapy schedules used), it is nonetheless possible to fit plausible-looking response curves. The methodology used here is based on a standard technique for analyzing dose-response in radiation therapy-alone studies and is capable of application to other mixed-modality treatment combinations involving radiation therapy.

  5. Impact of Toceranib/Piroxicam/Cyclophosphamide Maintenance Therapy on Outcome of Dogs with Appendicular Osteosarcoma following Amputation and Carboplatin Chemotherapy: A Multi-Institutional Study

    PubMed Central

    Mathie, Tamra; Stingle, Nicole; Portela, Roberta; Pennell, Michael L.; Clifford, Craig A.; Rosenberg, Mona P.; Vail, David M.; Williams, Laurel E.; Cronin, Kim L.; Wilson-Robles, Heather; Borgatti, Antonella; Henry, Carolyn J.; Bailey, Dennis B.; Locke, Jennifer; Northrup, Nicole C.; Crawford-Jakubiak, Martin; Gill, Virginia L.; Klein, Mary K.; Ruslander, David M.; Thamm, Doug H.; Phillips, Brenda; Post, Gerald

    2015-01-01

    Background We hypothesized that the addition of toceranib to metronomic cyclophosphamide/piroxicam therapy would significantly improve disease-free interval (DFI) and overall survival (OS) in dogs with appendicular osteosarcoma (OSA) following amputation and carboplatin chemotherapy. Methods and Findings This was a randomized, prospective clinical trial in which dogs with OSA free of gross metastatic disease (n = 126) received carboplatin chemotherapy (4 doses) following amputation. On study entry, dogs were randomized to receive piroxicam/cyclophosphamide with or without toceranib (n = 63 each) after completing chemotherapy. Patient demographics were not significantly different between both groups. During or immediately following carboplatin chemotherapy, 32 dogs (n = 13 toceranib; n = 19 control) developed metastatic disease, and 13 dogs left the study due to other medical conditions or owner preference. Following carboplatin chemotherapy, 81 dogs (n = 46 toceranib; n = 35 control) received the metronomic treatment; 35 dogs (n = 20 toceranib; n = 15 control) developed metastatic disease during the maintenance therapy, and 26 dogs left the study due to other medical conditions or owner preference. Nine toceranib-treated and 11 control dogs completed the study without evidence of metastatic disease 1-year following amputation. Toceranib-treated dogs experienced more episodes of diarrhea, neutropenia and weight loss than control dogs, although these toxicities were low-grade and typically resolved with supportive care. More toceranib-treated dogs (n = 8) were removed from the study for therapy-associated adverse events compared to control dogs (n = 1). The median DFI for control and toceranib treated dogs was 215 and 233 days, respectively (p = 0.274); the median OS for control and toceranib treated dogs was 242 and 318 days, respectively (p = 0.08). The one year survival rate for control dogs was 35% compared to 38% for dogs receiving toceranib. Conclusions The

  6. A metronomic schedule as salvage chemotherapy for upper gastrointestinal tract cancer.

    PubMed

    Roberto, Michela; Romiti, Adriana; Onesti, Concetta E; D'Antonio, Chiara; Milano, Annalisa; Falcone, Rosa; Barucca, Viola; Palombi, Lucia; Righini, Riccardo; Marchetti, Paolo

    2016-02-01

    In recent years, metronomic chemotherapy, consisting of continuous administration of low doses of cytotoxic agents, has being used as rescue therapy for different tumours. The aim of this study was to retrospectively assess the efficacy and safety of low-dose metronomic, oral capecitabine in pretreated or frail patients with recurrent upper gastrointestinal tract cancer. Patients with pretreated upper gastrointestinal tract cancer or who were not candidates for standard chemotherapy because of toxicity concerns received capecitabine at 1500 mg per day continuously until disease progression or occurrence of toxicity. Forty-seven patients (25 oesophagogastric cancer, 22 pancreatobiliary cancer; 25 men, 22 women; median age 69 years, range 42-90) were included in the study. Forty-five percent of the patients had received at least two previous lines of treatment and the median number of previous treatments was 1 (range 0-5). Twelve (31.6%) patients achieved clinical benefit (one partial response, 11 stable disease), whereas nine (23.7%) patients were progression free for at least 6 months. In an exploratory analysis, there was a significant relationship between performance status and clinical benefit (hazard ratio=8.25; P=0.01). The median overall survival was 5 months. A good performance status was associated with a longer survival (hazard ratio=0.26; P<0.01). No severe toxicity or treatment-related death was reported. Metronomic capecitabine showed good safety and moderate activity in frail or pretreated patients with advanced, upper gastrointestinal tract cancer. PMID:26473528

  7. A New mouthwash for Chemotherapy Induced Stomatitis

    PubMed Central

    Miranzadeh, Sedigheh; Adib-Hajbaghery, Mohsen; Soleymanpoor, Leyla; Ehsani, Majid

    2014-01-01

    Background: Stomatitis is a disturbing side-effect of chemotherapy that disturbs patients and causes difficulties in patient’s drinking, eating and talking, and may results in infection and bleeding. Objectives: This study aimed to investigate the effect of Yarrow distillate in the treatment of chemotherapy-induced stomatitis. Patients and Methods: This randomized controlled trial study was conducted during 2013. The study population consisted of all cancer patients with chemotherapy-induced oral stomatitis referred to Shahid Beheshti Medical Center, Kashan, Iran. The data collection instrument had two-part; a demographic part and another part recording the severity of the stomatitis at the first, seventh, and 14th days of the intervention based on a WHO criteria checklist in 2005. In this study, 56 patients diagnosed with cancer were randomly assigned into control and experimental groups in similar blocks according to their stomatitis severity. The experimental group gargled 15 mL of a routine solution mixed with Yarrow distillate 4 times a day for 14 days while the control group gargled 15 mL of routine solution. The severity of stomatitis was assessed at the beginning of the intervention, and then after 7 and 14 days of the study. Data were analyzed using chi-square and Fisher exact test, Mann-Whitney U, Kruskal-Wallis, and Friedman tests using SPSS 11.5 software. Results: At first, the median score of stomatitis in the experimental group was 2.50 that significantly reduced to 1 and 0 in days 7 and 14 of the intervention, respectively (P value < 0.001). However, in the control group, the median score of stomatitis was 2.50, which significantly increased to 3 in days 7 and 14 (P value < 0.001). Conclusions: Yarrow distillate-contained solution reduced stomatitis severity more than the routine solution. Therefore, we suggest using it in patients with chemotherapy-induced stomatitis. PMID:25699281

  8. The effect of training during treatment with chemotherapy on muscle strength and endurance capacity: A systematic review.

    PubMed

    Van Moll, Christel C A; Schep, Goof; Vreugdenhil, Art; Savelberg, Hans H C M; Husson, Olga

    2016-05-01

    Background Treatment of cancer with chemotherapy decreases endurance capacity and muscle strength. Training during chemotherapy might prevent this. There are no clear guidelines concerning which type of training and which training dose are effective. This review aims to gain insight into the different training modalities during chemotherapy and the effects of such training to improve endurance capacity and muscle strength in order to obtain the knowledge to compose a future training program which trains cancer patients in the most effective way. Material and methods A systematic search of PubMed was carried out. In total, 809 studies of randomized controlled trials studying the effects of training during chemotherapy on endurance capacity and muscle strength were considered. Only 14 studies met all the inclusion criteria. The studies were assessed on methodological quality by using Cochrane criteria for randomized controlled trials. Results The quality of the studies was generally poor and the study populations varied considerably as the training programs were very heterogeneous. Variables of endurance capacity reported beneficial effects in 10 groups (59%). Increases due to training ranged from 8% to 31%. Endurance capacity decreased in nine of 13 control groups (69%), which ranged from 1% to 32%. Muscle strength improved significantly in 17 of 18 intervention groups (94%), ranging from 2% to 38%. Muscle strength also improved in 11 of 14 control groups (79%), but this increase was only minimal, ranging from 1.3% to 6.5%. Conclusions This review indicates that training during chemotherapy may help in preventing the decrease in muscle strength and endurance capacity. It is important to know which training intensity and duration is the most effective in training cancer patients, to provide a training program suitable for every cancer patient. Training should be based on good research and should be implemented into international guidelines and daily practice. More

  9. Chemotherapy for Soft Tissue Sarcomas

    MedlinePlus

    ... drugs may be used as well, including cisplatin, dacarbazine (DTIC), docetaxel (Taxotere ® ), gemcitabine (Gemzar ® ), methotrexate, oxaliplatin, paclitaxel (Taxol ® ), ... such as: MAID (mesna, Adriamycin [doxorubicin], ifosfamide, and dacarbazine). Chemotherapy drugs kill cancer cells but also damage ...

  10. Pathobiology of cancer chemotherapy-induced peripheral neuropathy (CIPN)

    PubMed Central

    Han, Yaqin; Smith, Maree T.

    2013-01-01

    Chemotherapy induced peripheral neuropathy (CIPN) is a type of neuropathic pain that is a major dose-limiting side-effect of potentially curative cancer chemotherapy treatment regimens that develops in a “stocking and glove” distribution. When pain is severe, a change to less effective chemotherapy agents may be required, or patients may choose to discontinue treatment. Medications used to alleviate CIPN often lack efficacy and/or have unacceptable side-effects. Hence the unmet medical need for novel analgesics for relief of this painful condition has driven establishment of rodent models of CIPN. New insights on the pathobiology of CIPN gained using these models are discussed in this review. These include mitochondrial dysfunction and oxidative stress that are implicated as key mechanisms in the development of CIPN. Associated structural changes in peripheral nerves include neuronopathy, axonopathy and/or myelinopathy, especially intra-epidermal nerve fiber (IENF) degeneration. In patients with CIPN, loss of heat sensitivity is a hallmark symptom due to preferential damage to myelinated primary afferent sensory nerve fibers in the presence or absence of demyelination. The pathobiology of CIPN is complex as cancer chemotherapy treatment regimens frequently involve drug combinations. Adding to this complexity, there are also subtle differences in the pathobiological consequences of commonly used cancer chemotherapy drugs, viz platinum compounds, taxanes, vincristine, bortezomib, thalidomide and ixabepilone, on peripheral nerves. PMID:24385965

  11. Glutamine: A novel approach to chemotherapy-induced toxicity

    PubMed Central

    Gaurav, Kumar; Goel, R. K.; Shukla, Mridula; Pandey, Manoj

    2012-01-01

    Treatment of cancer is associated with short- and long-term side-effects. Cancer produces a state of glutamine deficiency, which is further aggravated by toxic effects of chemotherapeutic agents leading to increased tolerance of tumor to chemotherapy as well as reduced tolerance of normal tissues to the side-effects of chemotherapy. This article reviews the possible role of glutamine supplementation in reducing the serious adverse events in patients treated with anticancer drugs. The literature related to the possible role of glutamine in humans with cancer and the supportive evidence from animal studies was reviewed. Searches were made and the literature was retrieved using PUBMED, MEDLINE, COCHRANE LIBRARY, CENAHL and EMBASE, with a greater emphasis on the recent advances and clinical trials. Glutamine supplementation was found to protect against radiation-induced mucositis, anthracycline-induced cardiotoxicity and paclitaxel-related myalgias/arthralgias. Glutamine may prevent neurotoxicity of paclitaxel, cisplatin, oxaplatin bortezomib and lenolidamide, and is beneficial in the reduction of the dose-limiting gastrointestinal toxic effects of irinotecan and 5-FU-induced mucositis and stomatitis. Dietary glutamine reduces the severity of the immunosuppressive effect induced by methotrexate and improves the immune status of rats recovering from chemotherapy. In patients with acute myeloid leukemia requiring parenteral nutrition, glycyl-glutamine supplementation could hasten neutrophil recovery after intensive myelosuppressive chemotherapy. Current data supports the usefulness of glutamine supplementation in reducing complications of chemotherapy; however, paucity of clinical trials weakens the clear interpretation of these findings. PMID:22754203

  12. Why do patients with weight loss have a worse outcome when undergoing chemotherapy for gastrointestinal malignancies?

    PubMed

    Andreyev, H J; Norman, A R; Oates, J; Cunningham, D

    1998-03-01

    The aim of this study was to examine whether weight loss at presentation, in patients who were to receive chemotherapy for gastrointestinal carcinomas, influences outcome and whether nutritional intervention would be worthwhile. This study was a retrospective review of prospectively gathered data. The outcomes of patients with or without weight loss and treated for locally advanced or metastatic tumours of the oesophagus, stomach, pancreas, colon or rectum were compared. In 1555 such consecutive patients treated over a 6-year period, weight loss at presentation was reported more commonly by men than women (51 versus 44%, P = 0.01). Although patients with weight loss received lower chemotherapy doses initially, they developed more frequent and more severe dose limiting toxicity--specifically plantar-palmar syndrome (P < 0.0001) and stomatitis (P < 0.0001)--than patients without weight loss. Consequently, patients with weight loss on average received 1 month (18%) less treatment (P < 0.0001). Weight loss correlated with shorter failure-free (P < 0.0001, hazard ratio = 1.25) and overall survival (P < 0.0001, hazard ratio = 1.63), decreased response (P = 0.006), quality of life (P < 0.0001) and performance status (P < 0.0001). Patients who stopped losing weight had better overall survival (P = 0.0004). Weight loss at presentation was an independent prognostic variable (hazard ratio = 1.43). The poorer outcome from treatment in patients with weight loss appears to occur because they receive significantly less chemotherapy and develop more toxicity rather than any specifically reduced tumour responsiveness to treatment. These findings provide a rationale for attempting randomised nutritional intervention studies in these patients. PMID:9713300

  13. Dosimetric Evaluation and Treatment Outcome of Intensity Modulated Radiation Therapy After Doxorubicin-Based Chemotherapy for Primary Mediastinal Large B-Cell Lymphoma

    SciTech Connect

    Xu, Li-Ming; Li, Ye-Xiong; Fang, Hui; Jin, Jing; Wang, Wei-Hu; Wang, Shu-Lian; Liu, Yue-Ping; Song, Yong-Wen; Liu, Qing-Feng; Chen, Bo; Qi, Shu-Nan; Ren, Hua; Dai, Jian-Rong

    2013-04-01

    Purpose: The value of intensity-modulated radiation therapy (IMRT) after doxorubicin-based chemotherapy in primary mediastinal large B-cell lymphoma (PMBCL) is unknown. We assessed the dosimetric parameters, treatment outcomes, and toxicity of IMRT in PMBCL. Methods and Materials: Forty-one PMBCL patients underwent mediastinal IMRT after doxorubicin-based chemotherapy. Thirty-eight patients had stage I-II disease, and 3 patients had stage III-IV disease. Most patients presented with bulky mediastinal disease (65.9%) and local invasion (82.9%). The dose-volume histograms of the target volume and critical normal structures were evaluated. Results: The average planning target volume (PTV) mean dose was 39 Gy. Only 0.5% and 1.4% of the PTV received <90% and <95% of the prescribed dose, respectively, indicating excellent target coverage. The median mean lung dose and percentage lung volume receiving 20 Gy (V20) were 16.3 Gy and 30.6%. The 5-year overall survival (OS) and local control (LC) were 95.1% and 89.8%. After chemotherapy, consolidation radiation therapy in patients with complete/partial response resulted in significantly better survival than salvage radiation therapy in patients with stable/progressive disease (3-year OS 100% vs 75%; 3-year LC 96.6% vs 62.5%). No grade 4 or 5 acute or late toxicities occurred. Conclusions: Mediastinal IMRT after doxorubicin-based chemotherapy can be safely and efficiently delivered, and it provides favorable outcomes in PMBCL patients with a large target volume and high-risk features.

  14. AB058. Intravenous chemotherapy combined with intravesical chemotherapy to treat T1G3 bladder urothelial carcinoma after transurethral resection of bladder tumor: results of a retrospective study

    PubMed Central

    Zhang, Yu; Hu, Hailong; Tian, Dawei; Wu, Changli

    2016-01-01

    Objective The management of stage 1 and grade 3 (T1G3) bladder cancer continues to be controversial. Although the transurethral resection of bladder tumor (TURBT) followed by intravesical chemotherapy is a conservative strategy for treatment of T1G3 bladder cancer, a relatively high risk of tumor recurrence and progression remains regarding the therapy. This study aimed to compare the efficacy of intravenous chemotherapy combined with intravesical chemotherapy versus intravesical chemotherapy alone for T1G3 bladder cancer after TURBT surgery. Methods We retrospectively reviewed the cases of 457 patients who were newly diagnosed with T1G3 bladder urothelial carcinoma between January 2009 and March 2014. After TURBT, 281 patients received intravesical chemotherapy alone, whereas 176 patients underwent intravesical chemotherapy in combination with intravenous chemotherapy. Tumor recurrence and progression were monitored periodically by urine cytology and cystoscopy in follow-up. Recurrence-free survival and progression-free survival of the two chemotherapy strategies following TURBT were analyzed. Univariable and multivariable Cox hazards analyses were performed to predict the prognostic factors for tumor recurrence and progression. Results The tumor recurrence rate was 36.7% for patients who received intravesical chemotherapy alone after TURBT, compared with 19.9% for patients who received intravenous chemotherapy combined with intravesical chemotherapy after TURBT (P<0.001). The progression rate was 10.6% for patients who underwent intravesical chemotherapy alone and 2.3% for patients who underwent the combined chemotherapies (P=0.003). Kaplan-Meier curves showed significant differences in recurrence-free survival and progression-free survival between the two treatment strategies, with a log-rank P value of <0.001 and 0.003, respectively. Multivariable analyses revealed that intravenous chemotherapy was the independent prognostic factor for tumor recurrence and

  15. Intravenous chemotherapy combined with intravesical chemotherapy to treat T1G3 bladder urothelial carcinoma after transurethral resection of bladder tumor: results of a retrospective study

    PubMed Central

    Zhang, Yu; Xie, Linguo; Chen, Tao; Xie, Wanqin; Wu, Zhouliang; Xu, Hao; Xing, Chen; Sha, Nan; Shen, Zhonghua; Qie, Yunkai; Liu, Xiaoteng; Hu, Hailong; Wu, Changli

    2016-01-01

    Objective The management of stage 1 and grade 3 (T1G3) bladder cancer continues to be controversial. Although the transurethral resection of bladder tumor (TURBT) followed by intravesical chemotherapy is a conservative strategy for treatment of T1G3 bladder cancer, a relatively high risk of tumor recurrence and progression remains regarding the therapy. This study aimed to compare the efficacy of intravenous chemotherapy combined with intravesical chemotherapy versus intravesical chemotherapy alone for T1G3 bladder cancer after TURBT surgery. Methods We retrospectively reviewed the cases of 457 patients who were newly diagnosed with T1G3 bladder urothelial carcinoma between January 2009 and March 2014. After TURBT, 281 patients received intravesical chemotherapy alone, whereas 176 patients underwent intravesical chemotherapy in combination with intravenous chemotherapy. Tumor recurrence and progression were monitored periodically by urine cytology and cystoscopy in follow-up. Recurrence-free survival and progression-free survival of the two chemotherapy strategies following TURBT were analyzed. Univariable and multivariable Cox hazards analyses were performed to predict the prognostic factors for tumor recurrence and progression. Results The tumor recurrence rate was 36.7% for patients who received intravesical chemotherapy alone after TURBT, compared with 19.9% for patients who received intravenous chemotherapy combined with intravesical chemotherapy after TURBT (P<0.001). The progression rate was 10.6% for patients who underwent intravesical chemotherapy alone and 2.3% for patients who underwent the combined chemotherapies (P=0.003). Kaplan–Meier curves showed significant differences in recurrence-free survival and progression-free survival between the two treatment strategies, with a log-rank P-value of <0.001 and 0.003, respectively. Multivariable analyses revealed that intravenous chemotherapy was the independent prognostic factor for tumor recurrence and

  16. [PIPAC--Pressurized intraperitoneal aerosol chemotherapy. A novel treatment for peritoneal carcinomatosis].

    PubMed

    Hübner, Martin; Teixeira, Hugo; Boussaha, Tarek; Cachemaille, Matthieu; Lehmann, Kuno; Demartines, Nicolas

    2015-06-17

    Peritoneal carcinomatosis remains a diagnostic challenge with sparse treatment options. The effect of systemic chemotherapy remains limited inside the peritoneum due to low penetration and a relative resistance of peritoneal nodules. Heated IntraPeritoneal Chemotherapy (HIPEC) improves survival in selected patients but entails a high incidence of complications. Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) allows to disperse the active agents inside the peritoneal cavity by laparoscopy. Distribution and tissue penetration of chemotherapy by PIPAC are superior to HIPEC and systemic chemotherapy despite of lower doses. Systemic side effects are uncommon and surgical trauma is limited. Histological and clinical response rates in platinum-resistant patients approach 70% and survival data appear to be favorable compared with standard therapy. PMID:26255492

  17. Intensified Adjuvant IFADIC Chemotherapy for Adult Soft Tissue Sarcoma: A Prospective Randomized Feasibility Trial

    PubMed Central

    Brodowicz, Thomas; Schwameis, Eva; Widder, Joachim; Amann, Gabriele; Wiltschke, Christoph; Dominkus, Martin; Windhager, Reinhard; Ritschl, Peter; Pötter, Richard; Kotz, Rainer

    2000-01-01

    Purpose. The present prospective randomized adjuvant trial was carried out to compare the toxicity, feasibility and efficacy of augmented chemotherapy added to hyperfractionated accelerated radiotherapy after wide or marginal resection of grade 2 and grade 3 soft tissue sarcoma (STS). Patients and methods. Fifty-nine patients underwent primary surgery by wide or marginal excision and were subsequently randomized to receive radiotherapy alone or under the addition of six courses of ifosfamide (1500 mg/m2 , days 1–4), dacarbazine (DTIC) (200 mg/m2 , days 1–4) and doxorubicin (25 mg/m2 , days 1–2) administered in 14-day-intervals supported by granulocyte-colony stimulating factor (30 × 106 IU/day, s.c.) on days 5–13. According to the randomization protocol, 28 patients received radiotherapy only, whereas 31 patients were treated with additional chemotherapy. Results. The relative ifosfamide–doxorubicin–DTIC (IFADIC) dose intensity achieved was 93%. After a mean observation period of 41±19.7 months (range, 8.1–84 months), 16 patients (57%) in the control group versus 24 patients (77%) in the chemotherapy group were free of disease (p>0.05).Within the control group, tumor relapses occurred in 12 patients (43%;six patients with distant metastases, two with local relapse, four with both) versus seven patients (23%; five patients with distant metastases, one with local recurrence, one with both) from the chemotherapy group. Relapse-free survival (RFS) (p=0.1), time to local failure (TLF) (p=0.09), time to distant failure (TDF) (p=0.17) as well as overall survival (OS) (p=0.4) did not differ significantly between the two treatment groups. Treatment-related toxicity was generally mild in both treatment arms. Conclusion. We conclude that the safety profile of intensified IFADIC added to radiotherapy was manageable and tolerable in the current setting. Inclusion of intensified IFADIC was not translated into a significant benefit concerning OS, RFS, TLF and

  18. The double-edged sword: Neurotoxicity of chemotherapy.

    PubMed

    Magge, Rajiv S; DeAngelis, Lisa M

    2015-03-01

    The number of available therapies for hematologic malignancies continues to grow at a rapid pace. Unfortunately, many of these treatments carry both central and peripheral nervous system toxicities, potentially limiting a patient's ability to tolerate a full course of treatment. Neurotoxicity with chemotherapy is common and second only to myelosuppression as a reason to limit dosing. This review addresses the neurotoxicity of newly available therapeutic agents including brentuximab vedotin and blinatumomab as well as classic ones such as methotrexate, vinca alkaloids and platinums. Although peripheral neuropathy is common with many drugs, other complications such as seizures and encephalopathy may require more immediate attention. Rapid recognition of adverse neurologic effects may lead to earlier treatment and appropriate adjustment of dosing regimens. In addition, knowledge of common toxicities may help differentiate chemotherapy-related symptoms from actual progression of cancer into the CNS. PMID:25445718

  19. Role of chemotherapy in the management of advanced thymic tumors.

    PubMed

    Evans, Tracey L; Lynch, Thomas J

    2005-01-01

    Chemotherapy has an important role in the treatment of advanced thymic tumors. Early stage tumors are successfully treated with surgery. Locally advanced tumors (Masaoka stage III and IVA) are often treated with combined modality treatment including surgery, radiation, and chemotherapy. For patients with curable thymic tumors, the ability to attain a complete resection is a critical prognostic factor. Locally advanced tumors have a relatively high risk of recurrence and decreased rates of long-term survival. A multimodality approach including induction chemotherapy and postoperative radiation therapy can improve complete resection rates and long-term outcomes. Thymic tumors are chemoresponsive with optimal responses achieved with cisplatin-based combination chemotherapy. Chemotherapy with radiation can result in long-term progression-free survival for patients with locally advanced disease who remain inoperable following induction therapy. Patients with disseminated (stage IVB) thymic tumors can also have significant disease response and palliation of symptoms when treated with chemotherapy. Octreotide and corticosteroids also have shown efficacy. For best results, it is important that thoracic surgeons, radiation oncologists, and medical oncologists work together to obtain the best local control of tumor and optimal treatment of metastases. PMID:16104360

  20. Therapeutic efficacy of 177Lu-CHX-A″-DTPA-hu3S193 radioimmunotherapy in prostate cancer is enhanced by EGFR inhibition or docetaxel chemotherapy

    PubMed Central

    Kelly, Marcus P; Lee, Sze Ting; Lee, F-T; Smyth, Fiona E; Davis, Ian D.; Brechbiel, Martin W; Scott, Andrew M

    2008-01-01

    Background This study investigated the biodistribution and therapeutic efficacy of Lutetium-177 (177Lu) radiolabeled anti-Lewis Y monoclonal antibody hu3S193 radioimmunotherapy (RIT) in mice bearing prostate cancer xenografts. The ability of Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitor AG1478 and docetaxel chemotherapy to enhance the efficacy of RIT was also assessed in vivo. Methods The in vitro cytotoxicity of 177Lu labeled hu3S193 on Ley positive DU145 prostate cancer cells was assessed using proliferation assays, with induction of apoptosis measured by ELISA. The in vivo biodistribution and tumor localization of 177Lu-hu3S193 was assessed in mice bearing established DU145 tumor xenografts. The efficacy and maximum tolerated dose of 177Lu-hu3S193 RIT in vivo was determined by a dose escalation study. EGFR inhibitor AG1478 or docetaxel chemotherapy was administered at sub-therapeutic doses in conjunction with RIT in vivo. Results 177Lu-hu3S193 mediated significant induction of cytotoxicity and apoptosis in vitro. In vivo analysis of 177Lu-hu3S193 biodistribution demonstrated specific targeting of DU145 prostate cancer xenografts, with maximal tumor uptake of 33.2 ± 3.9 %ID/g observed at 120 hr post injection. In RIT studies, 177Lu-hu3S193 caused specific and dose-dependent inhibition of prostate cancer tumor growth. A maximum tolerated dose of 350μCi was determined for 177Lu-hu3S193. Combination of 177Lu-hu3S193 RIT with EGFR inhibitor AG1478 or docetaxel chemotherapy both significantly improved efficacy. Conclusions 177Lu-hu3S193 RIT is effective as a single agent in the treatment of Ley positive prostate cancer models. The enhancement of RIT by AG1478 or docetaxel indicates the promise of combined modality strategies. PMID:18942092

  1. Effect of local hyperthermia of the bladder on mitomycin C pharmacokinetics during intravesical chemotherapy for the treatment of superficial transitional cell carcinoma

    PubMed Central

    Paroni, Rita; Salonia, Andrea; Lev, Avigdor; Da Pozzo, Luigi Filippo; Cighetti, Giuliana; Montorsi, Francesco; Rigatti, Patrizio; Colombo, Renzo

    2001-01-01

    Aims To assess the effect of local hyperthermia on the systemic absorption of mitomycin C (MMC) during intravesical chemotherapy for the treatment of superficial transitional cell carcinoma of the bladder, and to establish the likely safety of this procedure. Methods Group 1 (n = 12) received 20 mg intravesical MMC plus local hyperthermia, group 2 (n = 13) 20 mg MMC alone, group 3 (n = 16) 40 mg MMC plus local hyperthermia and group 4 (n = 10) 40 mg MMC alone. Patients in groups 1, 2, and 4 underwent post-tumour resection adjuvant treatment, whereas those in group 3 still had tumour present and were treated to eradicate it. Intravesical instillation lasted 60 min, with the solution (50 ml) being replaced after the first 30 min. Blood samples were taken before, and every 15 min during instillation. MMC concentrations in plasma and in urine were determined by h.p.l.c. Results The highest MMC plasma concentration (67.9 ng ml−1) occurred in a patient in group 3. This value was well below the threshold concentration (400 ng ml−1) for myelosuppression. Local hyperthermia associated with the intravesical chemotherapy enhanced plasma MMC concentrations at 30, 45 and 60 min compared with chemotherapy alone (Group 1 vs 2, P ≤ 0.008). Systemic exposure to MMC was not significantly increased by doubling the intravesical dose when intravesical chemotherapy alone was administered. Patients in group 3 displayed the highest degree of MMC absorption and the greatest variability in pharmacokinetics between patients. Conclusions Local hyperthermia enhances the systemic absorption of MMC during intravesical chemotherapy for bladder cancer. In the doses used, plasma MMC concentrations were always more than six times lower than those shown to cause toxicity. PMID:11560559

  2. Transfer factors as immunotherapy and supplement of chemotherapy in experimental pulmonary tuberculosis

    PubMed Central

    FABRE, R A; PÉREZ, T M; AGUILAR, L D; RANGEL, M J; ESTRADA-GARCÌA, I; HERNÁNDEZ-PANDO, R; ESTRADA PARRA, S

    2004-01-01

    Problems of logistics, compliance and drug resistance point to an urgent need for immunotherapeutic strategies capable of shortening the current six month antibiotic regimens used to treat tuberculosis. One potential immunotherapeutic agent is transfer factors. Transfer factors (TF) are low molecular weight dialysable products from immune cells which transmit the ability to express delayed-type hypersensitivity (DTH) and cell mediated immunity from sensitized donors to nonimmune recipients. In this study we determined the efficiency of TF as immunotherapy to treat experimental tuberculosis. When BALB/c mice are infected via the trachea with Mycobacterium tuberculosis H37Rv there is an initial phase of partial resistance dominated by Th-1 type cytokines plus tumour necrosis factor-alpha (TNFα) and the inducible isoform of nitric oxide synthase (iNOS), followed by a phase of progressive disease characterized by increasing expression of IL-4, diminished expression of TNFα and iNOS, and low DTH. Animals in this late progressive phase of the disease (day 60) were treated with different doses of TF (one injection per week) obtained from spleen cells when the peak of immune protection in this animal model is reached (day 21), or with different doses of TF from peripheral leucocytes of PPD + healthy subjects. We show here that the treatment with murine or human TF restored the expression of Th-1 cytokines, TNFα and iNOS provoking inhibition of bacterial proliferation and significant increase of DTH and survival. This beneficial effect was dose dependent. Interestingly, murine TF in combination with conventional chemotherapy had a synergistic effect producing significant faster elimination of lung bacteria loads than chemotherapy alone. PMID:15086383

  3. MLN2238, a proteasome inhibitor, induces caspase-dependent cell death, cell cycle arrest, and potentiates the cytotoxic activity of chemotherapy agents in rituximab-chemotherapy-sensitive or rituximab-chemotherapy-resistant B-cell lymphoma preclinical models.

    PubMed

    Gu, Juan J; Hernandez-Ilizaliturri, Francisco J; Mavis, Cory; Czuczman, Natalie M; Deeb, George; Gibbs, John; Skitzki, Joseph J; Patil, Ritesh; Czuczman, Myron S

    2013-11-01

    To further develop therapeutic strategies targeting the proteasome system, we studied the antitumor activity and mechanisms of action of MLN2238, a reversible proteasome inhibitor, in preclinical lymphoma models. Experiments were conducted in rituximab-chemotherapy-sensitive cell lines, rituximab-chemotherapy-resistant cell lines (RRCL), and primary B-cell lymphoma cells. Cells were exposed to MLN2238 or caspase-dependent inhibitors, and differences in cell viability, alterations in apoptotic protein levels, effects on cell cycle, and the possibility of synergy when combined with chemotherapeutic agents were evaluated. MLN2238 showed more potent dose-dependent and time-dependent cytotoxicity and inhibition of cell proliferation in lymphoma cells than bortezomib. Our data suggest that MLN2238 can induce caspase-independent cell death in RRCL. MLN2238 (and to a much lesser degree bortezomib) reduced RRCL S phase and induced cell cycle arrest in the G2/M phase. Exposure of rituximab-chemotherapy-sensitive cell lines and RRCL to MLN2238 potentiated the cytotoxic effects of gemcitabine, doxorubicin, and paclitaxel and overcame resistance to chemotherapy in RRCL. MLN2238 is a potent proteasome inhibitor active in rituximab-chemotherapy-sensitive and rituximab-chemotherapy-resistant cell models and potentiates the antitumor activity of chemotherapy agents and has the potential of becoming an effective therapeutic agent in the treatment of therapy-resistant B-cell lymphoma. PMID:23995855

  4. Chemotherapy plus Erlotinib versus Chemotherapy Alone for Treating Advanced Non-Small Cell Lung Cancer: A Meta-Analysis

    PubMed Central

    Xu, J. L.; Jin, B.; Ren, Z. H.; Lou, Y. Q.; Zhou, Z. R.; Yang, Q. Z.; Han, B. H.

    2015-01-01

    Background Whether a combination of chemotherapy and erlotinib is beneficial for advanced non-small cell lung cancer (NSCLC) remains controversial. This study aimed to summarize the currently available evidence and compare the efficacy and safety of chemotherapy plus erlotinib versus chemotherapy alone for treating advanced NSCLC. Methods EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials were searched for relevant studies. Our protocol was registered in PROSPERO (CRD42014015015). Results Nine randomized controlled trials with a total of 3599 patients were included. Compared to chemotherapy alone, chemotherapy plus erlotinib was superior in PFS (HR = 0.76 [95% CI 0.62, 0.92], P = 0.006), and no statistically significant difference was observed in OS (HR = 0.94 [95% CI 0.86, 1.03], P = 0.16). Intercalated erlotinib plus chemotherapy demonstrated improvements in PFS (HR = 0.67 [95% CI 0.50, 0.91], P = 0.009) and OS (HR = 0.82 [95% CI 0.69, 0.98], P = 0.03). Continuous erlotinib plus chemotherapy treatment failed to demonstrate improvements in PFS (HR = 0.91 [95% CI 0.80, 1.04], P = 0.16) and OS (HR = 0.98 [95% CI 0.89, 1.09], P = 0.75). The association of chemotherapy plus erlotinib with improvement in PFS was significant in never smoking patients (HR = 0.46 [95% CI 0.37, 0.56], P<0.00001) but not in smoking patients (HR = 0.70 [95% CI 0.49, 1.00], P = 0.05). Among patients with EGFR mutant tumors, chemotherapy plus erlotinib demonstrated significant improvements in PFS (HR = 0.31 [95% CI 0.17, 0.58], P = 0.0002) and OS (HR = 0.52 [95% CI 0.30, 0.88], P = 0.01). Among patients with EGFR wild-type tumors, no statistically significant difference was observed with respect to PFS (HR = 0.87 [95% CI 0.70, 1.08], P = 0.21) and OS (HR = 0.78 [95% CI 0.59, 1.01], P = 0.06). Conclusion Combination of chemotherapy and erlotinib is a viable treatment option for patients with NSCLC, especially for patients who never smoked and patients with EGFR mutation

  5. Hematopoietic stem cell compartment: Acute and late effects of radiation therapy an chemotherapy<