Science.gov

Sample records for cisplatin based chemotherapy

  1. 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

  2. Administration of contrast media just before cisplatin-based chemotherapy increases cisplatin-induced nephrotoxicity.

    PubMed

    Sendur, M A N; Aksoy, S; Yaman, S; Arik, Z; Tugba Kos, F; Akinci, M B; Civelek, B; Yildirim Ozdemir, N; Uncu, D; Zengin, N

    2013-01-01

    There is a clinical need to predict the probability of cisplatin-induced nephrotoxicity (CIN) in order to make decisions about patient management and relevant preventive measures. The purpose of this study was to develop a risk prediction methodology of CIN. 197 consecutive cancer patients, whose serum creatinine was measured at least 48 h before every cycle of cisplatin-based chemotherapy, were included in the study. Demographic and clinical data were collected from the patient medical records. Renal function was evaluated at least 48 h before treatment (day 0) of each cycle, based on the Modification of Diet in Renal Disease (MDRD) formula. CIN was defined as a decrease of ≥ 25% in glomerular filtration rate (GFR) compared to baseline GFR values. The mean age of the study population was 54.5±9.6 years. Fifty-eight patients (29.4%) whose GFR had decreased by at least 25% compared to baseline values formed the CIN group, and the remaining 139 patients formed the non-CIN group. No significant differences were noted between the CIN and non-CIN groups in terms of age, gender, body mass index and smoking history. Metastatic disease was similar in both groups (p=0.86). History of hypertension (p=0.81), diabetes mellitus (p=0.72), and cardiovascular disease (p=0.58) were similar in the two groups. Chemotherapeutic agents used concurrently with cisplatin were similar in both groups. Significantly more radiologic examinations using contrast media were performed in the CIN group compared with the non-CIN group (p=0.01). In patients exposed to contrast media within a week before cisplatin administration, the risk of CIN was 2.56-fold higher (957 percent; CI 1.28-5.11) than in patients without such exposure (p=0.009). In patients with exposure to contrast media within a week before cisplatin administration, the risk of CIN was significantly higher than in patients without such an exposure. No additional risk factors for CIN were found in this retrospective observational

  3. Predictive Factors for Developing Venous Thrombosis during Cisplatin-Based Chemotherapy in Testicular Cancer.

    PubMed

    Heidegger, Isabel; Porres, Daniel; Veek, Nica; Heidenreich, Axel; Pfister, David

    2017-01-01

    Malignancies and cisplatin-based chemotherapy are both known to correlate with a high risk of venous thrombotic events (VTT). In testicular cancer, the information regarding the incidence and reason of VTT in patients undergoing cisplatin-based chemotherapy is still discussed controversially. Moreover, no risk factors for developing a VTT during cisplatin-based chemotherapy have been elucidated so far. We retrospectively analyzed 153 patients with testicular cancer undergoing cisplatin-based chemotherapy at our institution for the development of a VTT during or after chemotherapy. Clinical and pathological parameters for identifying possible risk factors for VTT were analyzed. The Khorana risk score was used to calculate the risk of VTT. Student t test was applied for calculating the statistical significance of differences between the treatment groups. Twenty-six out of 153 patients (17%) developed a VTT during chemotherapy. When we analyzed the risk factors for developing a VTT, we found that Lugano stage ≥IIc was significantly (p = 0.0006) correlated with the risk of developing a VTT during chemotherapy. On calculating the VTT risk using the Khorana risk score model, we found that only 2 out of 26 patients (7.7%) were in the high-risk Khorana group (≥3). Patients with testicular cancer with a high tumor volume have a significant risk of developing a VTT with cisplatin-based chemotherapy. The Khorana risk score is not an accurate tool for predicting VTT in testicular cancer. © 2017 S. Karger AG, Basel.

  4. The association of Raynaud's syndrome with cisplatin-based chemotherapy - a meta-analysis.

    PubMed

    Mohokum, Melvin; Hartmann, Peter; Schlattmann, Peter

    2012-10-01

    Vasospastic disorders of the digital circulation such as the Raynaud's syndrome (RS) are known side-effects of treatment of cisplatin-based chemotherapy. The prevalence of RS in patients during treatment with cisplatin-based chemotherapy is not well-defined. The objective of this paper was to assess the prevalence of RS in patients receiving cisplatin-based chemotherapy - a meta-analysis of published data was performed. The PubMed database of the National Library of Medicine and ISI Web of Knowledge was used for studies dealing with RS and patients receiving cisplatin-based chemotherapy. The studies provided sufficient data to estimate the prevalence of RS in patients receiving cisplatin-based chemotherapy. A forest plot was determined by the revealed prevalences. Statistical analysis was based on methods for a random effects meta-analysis and a finite mixture model for proportions. Publication bias was investigated with the linear regression test (Egger's method). A meta-regression was conducted by the year of publication and latitude. 24 eligible studies, contributing data on 2749 subjects, were included in this meta-analysis. For RS in patients receiving cisplatin-based chemotherapy a pooled prevalence of 24% and 95% CI (0.175, 0.313) was obtained. A mixture model analysis found four latent classes. Statistically, publication bias was not present (p-value 0.74). The meta-regression indicated that the odds ratio increased when the latitude increased, too (p-value 0.011). Despite some heterogeneity there is a possible indication of an association between RS and patients receiving cisplatin-based chemotherapy. Copyright © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  5. SERPINB1 expression is predictive for sensitivity and outcome of cisplatin-based chemotherapy in melanoma

    PubMed Central

    Willmes, Christoph; Kumar, Rajiv; Becker, Jürgen C.; Fried, Isabella; Rachakonda, P. Sivaramakrishna; Poppe, Lidia M.; Hesbacher, Sonja; Schadendorf, Dirk; Sucker, Antje

    2016-01-01

    Despite of highly effective new therapeutic strategies, chemotherapy still is an important treatment option in metastatic melanoma. Since predictors of chemotherapy response are rare, drugs and regimens are currently chosen arbitrarily. The present study was aimed at the identification of molecular markers predicting the outcome of chemotherapy in melanoma. Tumor biopsies from metastatic lesions were collected from 203 stage IV melanoma patients prior to chemotherapy onset and used for gene expression profiling (n = 6; marker identification set), quantitative real-time PCR (n = 127; validation set 1), and immunohistochemistry on tissue microarrays (n = 70; validation set 2). The results were correlated to the tumors' in-vitro chemosensitivity and to the patients' in-vivo chemotherapy outcome. SERPINB1 was found to correlate to the in-vitro sensitivity to cisplatin-containing chemotherapy regimens (p = 0.005). High SERPINB1 gene expression was associated with favorable tumor response (p = 0.012) and prolonged survival (p = 0.081) under cisplatin-based chemotherapy. High SERPINB1 protein expression in tumor tissue from cisplatin-treated patients was associated with a favorable survival (p = 0.011), and proved as an independent predictor of survival (p = 0.008) by multivariate analysis. We conclude, that SERPINB1 expression, although not functionally involved, is predictive for the outcome of cisplatin-based chemotherapy in melanoma, and thus may be useful to personalize melanoma chemotherapy. PMID:26799424

  6. SERPINB1 expression is predictive for sensitivity and outcome of cisplatin-based chemotherapy in melanoma.

    PubMed

    Willmes, Christoph; Kumar, Rajiv; Becker, Jürgen C; Fried, Isabella; Rachakonda, P Sivaramakrishna; Poppe, Lidia M; Hesbacher, Sonja; Schadendorf, Dirk; Sucker, Antje; Schrama, David; Ugurel, Selma

    2016-03-01

    Despite of highly effective new therapeutic strategies, chemotherapy still is an important treatment option in metastatic melanoma. Since predictors of chemotherapy response are rare, drugs and regimens are currently chosen arbitrarily. The present study was aimed at the identification of molecular markers predicting the outcome of chemotherapy in melanoma. Tumor biopsies from metastatic lesions were collected from 203 stage IV melanoma patients prior to chemotherapy onset and used for gene expression profiling (n = 6; marker identification set), quantitative real-time PCR (n = 127; validation set 1), and immunohistochemistry on tissue microarrays (n = 70; validation set 2). The results were correlated to the tumors' in-vitro chemosensitivity and to the patients' in-vivo chemotherapy outcome. SERPINB1 was found to correlate to the in-vitro sensitivity to cisplatin-containing chemotherapy regimens (p = 0.005). High SERPINB1 gene expression was associated with favorable tumor response (p = 0.012) and prolonged survival (p = 0.081) under cisplatin-based chemotherapy. High SERPINB1 protein expression in tumor tissue from cisplatin-treated patients was associated with a favorable survival (p = 0.011), and proved as an independent predictor of survival (p = 0.008) by multivariate analysis. We conclude, that SERPINB1 expression, although not functionally involved, is predictive for the outcome of cisplatin-based chemotherapy in melanoma, and thus may be useful to personalize melanoma chemotherapy.

  7. Mitochondrial Transcription Factor A and Mitochondrial Genome as Molecular Targets for Cisplatin-Based Cancer Chemotherapy.

    PubMed

    Kohno, Kimitoshi; Wang, Ke-Yong; Takahashi, Mayu; Kurita, Tomoko; Yoshida, Yoichiro; Hirakawa, Masakazu; Harada, Yoshikazu; Kuma, Akihiro; Izumi, Hiroto; Matsumoto, Shinji

    2015-08-20

    Mitochondria are important cellular organelles that function as control centers of the energy supply for highly proliferative cancer cells and regulate apoptosis after cancer chemotherapy. Cisplatin is one of the most important chemotherapeutic agents and a key drug in therapeutic regimens for a broad range of solid tumors. Cisplatin may directly interact with mitochondria, which can induce apoptosis. The direct interactions between cisplatin and mitochondria may account for our understanding of the clinical activity of cisplatin and development of resistance. However, the basis for the roles of mitochondria under treatment with chemotherapy is poorly understood. In this review, we present novel aspects regarding the unique characteristics of the mitochondrial genome in relation to the use of platinum-based chemotherapy and describe our recent work demonstrating the importance of the mitochondrial transcription factor A (mtTFA) expression in cancer cells.

  8. Survival of patients with advanced urothelial cancer treated with cisplatin-based chemotherapy.

    PubMed Central

    Fosså, S. D.; Sternberg, C.; Scher, H. I.; Theodore, C. H.; Mead, B.; Dearnaley, D.; Roberts, J. T.; Skovlund, E.

    1996-01-01

    The aim of the present retrospective study was to assess long-term survival after cisplatin-based chemotherapy in 398 patients with advanced urothelial transitional cell carcinoma (TCC) treated at seven international oncological units. Various combinations of cisplatin, methotrexate, vinblastine (or vincristine) and doxorubicin were used. The complete response rate according to the WHO criteria was 17%. Partial responses were obtained in 42% of the patients. The overall cancer-related 2 year and 5 year survival rates were 21% and 11% respectively. Based on multivariate analyses, a good prognosis group could be identified comprising patients with a good performance status with disease confined to lymph nodes (14%) or patients with T4b disease only. These patients had a 28% 5 year survival rate, which, in part, has to be related to post-chemotherapy consolidation treatment in patients with pelvis-confined disease (radiotherapy, 26%; total cystectomy, 11%). Fifteen patients died of chemotherapy-related complications and in 16% of the patients toxicity led to discontinuation of treatment. Modern cisplatin-based chemotherapy leads to long-term survival and cure of selected patients with advanced urothelial transitional cancer. In routine clinical practice, chemotherapy should be offered to good prognosis patients; those presenting with a good performance status and a non-metastasising T4b tumour or with metastases confined to lymph nodes. Post-chemotherapy consolidation treatment by surgery or radiotherapy should always be considered. Such chemotherapy requires oncological expertise in order to avoid unnecessary toxicity. PMID:8932351

  9. Prometheus' spirit: quality survival in advanced hepatocellular carcinoma after gemcitabine and cisplatin-based chemotherapy.

    PubMed

    Doval, D C; Pande, S B; Sharma, J B; Pavithran, K; Jena, A; Vaid, A K

    2008-10-01

    In advanced virus-induced hepatocellular carcinoma (HCC) associated with cirrhosis, the average survival is four months. We report a 56-year-old man with a large-volume advanced HCC, in whom gemcitabine and cisplatin-based chemotherapy resulted in near-complete regression, and quality survival of 24 months.

  10. Predicting and preventing thromboembolic events in patients receiving cisplatin-based chemotherapy for germ cell tumours.

    PubMed

    Gizzi, Marco; Oberic, Lucie; Massard, Christophe; Poterie, Audrey; Gwenael, Le Teuff; Loriot, Yohann; Albiges, Laurence; Baciarello, Giulia; Michels, Judith; Bossi, Alberto; Blanchard, Pierre; Escudier, Bernard; Fizazi, Karim

    2016-12-01

    Patients with germ cell tumours (GCT) receiving cisplatin-based chemotherapy are at high risk of thromboembolic events (TEE). Previously, we identified serum lactate dehydrogenase (LDH) and body surface area (BSA) as independent predictive factors for TEE. The aim of this study was to validate these predictive factors and to assess the impact of thromboembolism prophylaxis in patients at risk of deep venous thrombosis (DVT). Between 2001 and 2014, 295 patients received first-line cisplatin-based chemotherapy for GCT. Preventive anticoagulation with low-molecular-weight heparin (LMWH) was progressively implemented in patients with predictive factors. Sixteen patients with evidence of TEE before starting chemotherapy were excluded from the analysis. Among 279 eligible patients, a TEE occurred in 38 (14%) consisting of DVT (n = 26), arterial thrombosis (n = 2), and superficial thrombophlebitis (n = 10). DVT occurred in 26 (12.7%) of 204 patients with risk factors versus two (2.6%) of 75 patients with no risk factors (p = 0.01). After a prevention protocol was progressively implemented from 2005, primary thromboprophylaxis was administered to 104 patients (68%) with risk factors. Among patients at risk (n = 151), the incidence of DVT decreased by roughly half when they received a LMWH: 9/97 (9.2%) and 9/54 (16.6%), respectively (p = 0.23). Patients with GCT who receive cisplatin-based chemotherapy are at risk of developing a TEE which can be predicted by elevated serum LDH. To our knowledge this is the first study exploring LMWH as thromboprophylaxis in GCT patients. A prospective trial testing prophylactic anticoagulation is warranted. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. A risk-adapted strategy of radiotherapy or cisplatin-based chemotherapy in stage II seminoma.

    PubMed

    Domont, Julien; Massard, Christophe; Patrikidou, Anna; Bossi, Alberto; de Crevoisier, Renaud; Rose, Mathieu; Wibault, Pierre; Fizazi, Karim

    2013-07-01

    Indications for radiotherapy and chemotherapy in stage II seminoma are currently debated. Since 1980, the policy at Institut Gustave Roussy was to treat patients with stage IIA-B disease with external radiotherapy and patients with stage IIB-C with cisplatin-based chemotherapy. In stage IIB disease, 3 cm was the usual tumor size threshold above which individual patients were considered for chemotherapy. During the period 1980-2001, 67 patients with stage II seminoma were treated: stage IIA (n = 5), stage IIB (n = 31), and stage IIC (n = 31). The median age was 40 years (range: 23-64). Among 37 patients who received radiotherapy, 5, 28, and 4 had a stage IIA, IIB, and IIC, respectively. Among 30 patients who received chemotherapy, 27 had a stage IIC. With a median follow-up of 9.4 years, 19 relapses (28%) occurred, including 11 and 8 cases treated with radiotherapy (30%) and chemotherapy (27%), respectively. The 5-year relapse-free survival was 71% (95% CI: 59-80). All but three relapses were salvaged with chemotherapy followed in selected cases by surgical resection of residual masses. Only 3 patients died of seminoma. The 5-year overall survival rate is 97% (95% CI: 89-99). Five patients subsequently developed a non-germ-cell second cancer, which occurred within the radiation field in 3 cases. With an overall survival rate of 97%, the overall outcome of patients with stage II seminoma managed according to this risk-adapted strategy is good. The possibility of extending the indications for chemotherapy to selected stage IIB seminoma patients needs to be further evaluated as potentially beneficial in terms of relapse risk. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Conventional Cisplatin-Based Combination Chemotherapy Is Effective in the Treatment of Metastatic Spermatocytic Seminoma with Extensive Rhabdomyosarcomatous Transformation

    PubMed Central

    Jeong, Yumun; Cheon, Jaekyung; Kim, Tae-Oh; Lim, Doo-Ho; Lee, Sunpyo; Cho, Young-Mi; Hong, Jun Hyuk; Lee, Jae Lyun

    2015-01-01

    A 52-year-old man was presented with a huge left testicular mass and palpable cervical lymphadenopathy with retroperitoneal lymph node enlargement on an abdominal computed tomography. A left radical orchiectomy and an ultrasound-guided neck node biopsy were performed. A pathological examination revealed spermatocytic seminoma with extensive rhabdomyosarcomatous transformation, a condition known to be highly resistant to platinum-based chemotherapy. The patient received four cycles of etoposide, ifosfamide and cisplatin (VIP) chemotherapy. A repeat computed tomography revealed a substantial regression consistent with a partial response. Retroperitoneal lymph node dissection was attempted, which revealed rhabdomyosarcoma; however, complete microscopic resection was not achieved. After surgery, the residual abdominal lymph node progressed and salvage paclitaxel, ifosfamide and cisplatin (TIP) chemotherapy was employed, which again achieved a partial response. Here, we present a first case report of a spermatocytic seminoma with extensive rhabdomyosarcomatous transformation and multiple metastatic lymphadenopathies that showed a favorable response to platinum-based systemic chemotherapy. PMID:25381827

  13. Conventional Cisplatin-Based Combination Chemotherapy Is Effective in the Treatment of Metastatic Spermatocytic Seminoma with Extensive Rhabdomyosarcomatous Transformation.

    PubMed

    Jeong, Yumun; Cheon, Jaekyung; Kim, Tae-Oh; Lim, Doo-Ho; Lee, Sunpyo; Cho, Young-Mi; Hong, Jun Hyuk; Lee, Jae Lyun

    2015-10-01

    A 52-year-old man was presented with a huge left testicular mass and palpable cervical lymphadenopathy with retroperitoneal lymph node enlargement on an abdominal computed tomography. A left radical orchiectomy and an ultrasound-guided neck node biopsy were performed. A pathological examination revealed spermatocytic seminoma with extensive rhabdomyosarcomatous transformation, a condition known to be highly resistant to platinum-based chemotherapy. The patient received four cycles of etoposide, ifosfamide and cisplatin (VIP) chemotherapy. A repeat computed tomography revealed a substantial regression consistent with a partial response. Retroperitoneal lymph node dissection was attempted, which revealed rhabdomyosarcoma; however, complete microscopic resection was not achieved. After surgery, the residual abdominal lymph node progressed and salvage paclitaxel, ifosfamide and cisplatin (TIP) chemotherapy was employed, which again achieved a partial response. Here, we present a first case report of a spermatocytic seminoma with extensive rhabdomyosarcomatous transformation and multiple metastatic lymphadenopathies that showed a favorable response to platinum-based systemic chemotherapy.

  14. The impact of paclitaxel or cisplatin-based chemotherapy on sympathetic skin response: a prospective study.

    PubMed

    Argyriou, A A; Koutras, A; Polychronopoulos, P; Papapetropoulos, S; Iconomou, G; Katsoulas, G; Makatsoris, T; Kalofonos, H P; Chroni, E

    2005-11-01

    The current study aimed to assess the viability of sympathetic sudomotor fibers in cancer patients treated with cisplatin or paclitaxel-based chemotherapy and to ascertain whether this method could contribute to the diagnostic sensitivity of conventional techniques. Sympathetic skin response (SSR) from the hand and sole of 23 cancer patients (nine females and 14 males, mean age 62.4 +/- 10.5 years) was recorded unilaterally before and after chemotherapy with six courses of cumulative cisplatin or paclitaxel containing regimens. Clinical and electrophysiological data were also collected and correlated with the SSR results. Twenty-three healthy subjects served as controls. SSR abnormalities were only present in patients with evidence of peripheral neuropathy assessed by conventional nerve conduction techniques. Three patients had absent SSR in the upper limb whilst six patients had absent SSR both in the upper and lower limbs. In the upper limb, the mean SSR latency was not significantly altered through time (P = 0.086). In the lower limb the mean delay from baseline to follow-up was significantly changed (P = 0.029). In patients, the mean SSR latency was significantly prolonged compared with controls in both upper limb (P = 0.001) and lower limb (P = 0.000). SSR abnormalities were strongly related to sensory conduction abnormalities as detected by conventional techniques (r = 0.39, P = 0.004). Our results showed that SSR does not seem to add to the diagnostic sensitivity of conventional techniques in chemotherapy-induced neuropathy. However, its role in the disclosure of small fibers neuropathy abnormalities is worth considering. Further studies are warranted to address this important issue.

  15. Ototoxicity After Intensity-Modulated Radiation Therapy and Cisplatin-Based Chemotherapy in Children With Medulloblastoma

    SciTech Connect

    Paulino, Arnold C.; Lobo, Mark; Teh, Bin S.; Okcu, M. Fatih; South, Michael; Butler, E. Brian; Su, Jack; Chintagumpala, Murali

    2010-12-01

    Purpose: To report the incidence of Pediatric Oncology Group (POG) Grade 3 or 4 ototoxicity in a cohort of patients treated with craniospinal irradiation (CSI) followed by posterior fossa (PF) and/or tumor bed (TB) boost using intensity-modulated radiation therapy (IMRT). Methods and Materials: From 1998 to 2006, 44 patients with medulloblastoma were treated with CSI followed by IMRT to the PF and/or TB and cisplatin-based chemotherapy. Patients with standard-risk disease were treated with 18 to 23.4 Gy CSI followed by either a (1) PF boost to 36 Gy and TB boost to 54 to 55.8 Gy or (2) TB boost to 55.8 Gy. Patients with high-risk disease received 36 to 39.6 Gy CSI followed by a (1) PF boost to 54 to 55.8 Gy, (2) PF boost to 45 Gy and TB boost to 55.8 Gy, or (3) TB boost to 55.8 Gy. Median audiogram follow-up was 41 months (range, 11-92.4 months). Results: POG Grade Ototoxicity 0, 1, 2, 3. and 4 was found in 29, 32, 11, 13. and 3 ears. respectively, with POG Grade 3 or 4 accounting for 18.2% of cases. There was a statistically significant difference in mean radiation dose (D{sub mean}) cochlea according to degree of ototoxicity, with D{sub mean} cochlea increasing with severity of hearing loss (p = 0.027). Conclusions: Severe ototoxicity was seen in 18.2% of ears in children treated with IMRT boost and cisplatin-based chemotherapy. Increasing dose to the cochlea was associated with increasing severity of hearing loss.

  16. Risk factors associated with ineligibility of adjuvant cisplatin-based chemotherapy after nephroureterectomy

    PubMed Central

    Shao, I-Hung; Lin, Yu-Hsiang; Hou, Chen-Pang; Juang, Horng-Heng; Chen, Chien-Lun; Chang, Phei-Lang; Tsui, Ke-Hung

    2014-01-01

    Purpose Radical nephroureterectomy (RNU) is a standard treatment for upper urinary tract urothelial carcinoma. However, RNU can result in decreased renal function and cannot be treated with adjuvant chemotherapy. We performed a risk group stratification analysis to determine the preoperative factors that are predictive of diminished renal function after RNU. Materials and methods We retrospectively evaluated the medical records of all patients who underwent nephroureterectomy for upper urinary tract urothelial carcinoma at the Chang Gung Memorial Hospital from 2001 to 2008. We analyzed the association between perioperative glomerular filtration rate and preoperative parameters including cancer characteristics, serum creatinine level, and kidney size measured on computed tomographic images. Results A total of 242 patients fulfilled the inclusion criteria. The average decrease in renal function 1 month after RNU was 19.7%. Using 60 mL/min/1.73 m2 as the eligibility cutoff for cisplatin-based chemotherapy, 42.1% of the population was eligible prior to nephroureterectomy, whereas following surgery only 15.2% remained eligible. Using a cutoff of 45 mL/min/1.73 m2, 59.9% of the cohort was eligible for fractionated cisplatin dosing preoperatively, whereas only 32.6% remained above the cutoff postoperatively. The most significant predictors of poor postoperative renal function were body mass index >25 kg/m2, age >65 years, contralateral kidney length less than 10 cm, and absence of ipsilateral hydronephrosis. Conclusion Our results suggest that older age, higher body mass index, smaller contralateral renal length, and absence of ipsilateral hydronephrosis are predictive of decreased renal function after RNU. PMID:25364228

  17. Changes in blood concentrations of trace metals in cancer patients receiving cisplatin-based chemotherapy

    PubMed Central

    Nakamura, Tsutomu; Takahashi, Minoru; Niigata, Riho; Yamashita, Kazuhiko; Kume, Manabu; Hirai, Midori; Yasui, Hiroyuki

    2016-01-01

    The administration of cisplatin (CDDP) may influence trace metal concentrations in body fluids. In order to test this hypothesis, the blood concentrations of trace metals were determined during the present study in eight Japanese esophageal and lung cancer patients receiving CDDP-based chemotherapy. The levels of manganese, iron (Fe), cobalt, copper, zinc (Zn), platinum and lead in the plasma were determined by inductively coupled plasma-mass spectrometry. In addition, the serum levels of Fe, transferrin and ferritin were evaluated. The baseline plasma concentration of Fe in patients with esophageal cancer was significantly lower than that in lung cancer patients (P=0.011), although there were no significant differences identified with respect to the plasma levels of other trace metals. The data obtained from six fasting patients without blood transfusion demonstrated that plasma concentrations of Fe increased 3.5-fold soon after CDDP treatment and returned to baseline levels ~10 days after therapy. The excessive Fe levels in the bloodstream induced changes in serum ferritin and transferrin levels. Furthermore, serum Zn levels increased 1.8-fold in the 1–3 days following CDDP treatment, and serum cystatin C levels transiently increased. These findings indicate that serum Fe and Zn levels may be useful to understanding the physiological responses in the early stages of CDDP-based chemotherapy, which may be associated with systemic inflammation and/or tissue distribution of CDDP. PMID:28105341

  18. 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.

  19. [Benefits of cisplatin-based polychemotherapy in non-small cell bronchogenic carcinoma. Kyushu Lung Cancer Chemotherapy Study Group].

    PubMed

    Ohta, M; Hara, N; Ichikawa, Y; Kanda, T; Shima, K; Tamura, K; Hokama, M

    1988-06-01

    We studied the efficacy of cisplatin-based polychemotherapy for non-small-cell lung cancer. One hundred nineteen patients with adenocarcinoma or large cell carcinoma were randomized to receive cyclophosphamide, adriamycin, cisplatin and mitomycin C (CAPM) or mitomycin C, cytosine arabinoside and tegafur (MCT), and 48 patients with squamous cell carcinoma were randomized to receive cisplatin, adriamycin and peplomycin (PAP) or mitomycin C, cyclophosphamide, tespamine, toyomycin and tegafur (MCTTT). Radiation was given to the chest in patients with stage I-III disease. The response rates were CAPM, 34.5%; MCT, 13.1% (p less than 0.01) and PAP, 63.3%; MCTTT, 42.3%. A significant difference in response rate between the CAPM and MCT regimens was observed only in stage IV patients and not in stage I-III patients. The median survival was 9.5 months in the CAPM arm vs. 6.5 months in the MCT arm (p less than 0.007), and 8.5 months in the PAP arm vs. 6.5 months in the MCTTT arm. Improved median survival for the CAPM regimen was noted only in stage IV patients and not in stage I-III patients when compared to patients given the MCT regimen, respectively. Nausea and vomiting were significantly increased in patients with cisplatin-based polychemotherapy. Myelosuppression was more severe with the CAPM regimen than with the other chemotherapy regimens. We concluded that cisplatin-based polychemotherapy, CAPM and PAP therapy were of more benefit to patients with disseminated non-small-cell lung cancer than MCT and MCTTT therapy.

  20. Amisulpride in the prevention of nausea and vomiting induced by cisplatin-based chemotherapy: a dose-escalation study.

    PubMed

    Herrstedt, Jørn; Summers, Yvonne; Daugaard, Gedske; Christensen, Thomas B; Holmskov, Karin; Taylor, Paul D; Fox, Gabriel M; Molassiotis, Alexander

    2017-08-11

    The purpose of this study was to investigate the antiemetic effect of the dopamine D2- and dopamine D3-receptor antagonist, amisulpride, in patients receiving cisplatin-based chemotherapy. This dose-finding, non-comparative study investigated the antiemetic effect and safety of increasing doses (2.5, 7.5 and 20 mg) of amisulpride against acute nausea and vomiting in the period 0-24 h after initiation of cisplatin-based chemotherapy. The 20 mg dose was also investigated in combination with the 5-HT3-receptor antagonist, ondansetron. The primary parameter was complete response (0-24 h), defined as no emesis and no need for rescue antiemetics. Secondary parameters were number of emetic episodes, severity of nausea and time to first emetic episode and start of nausea. A total of 51 patients were enrolled and evaluable. None of the 10 patients in the 2.5 and 7.5 mg groups obtained a CR. In the 20 mg monotherapy cohort, two of the 18 subjects (11%) had a CR, 3/18 (17%) had no emesis and 12/18 (67%) had no significant nausea. Seven subjects (39%) had no nausea at all (a VAS score < 5 mm). In the combination (ondansetron plus amisulpride) cohort, 19/23 (83%; 90% confidence interval: 65-94%) had a CR and 14/23 (61%) had no nausea at all. Amisulpride has antiemetic effect against cisplatin-induced acute nausea and vomiting. The effect against nausea is of particular interest. Randomised studies are warranted to further explore the effect and safety of amisulpride.

  1. Prevention of chemotherapy-induced vomiting in children receiving multiple-day cisplatin chemotherapy: A hospital-based, retrospective cohort study.

    PubMed

    Kishimoto, Kenji; Kawasaki, Keiichiro; Saito, Atsuro; Kozaki, Aiko; Ishida, Toshiaki; Hasegawa, Daiichiro; Kosaka, Yoshiyuki

    2017-09-01

    Optimal prevention of chemotherapy-induced vomiting (CIV) has not been established for patients receiving cisplatin in divided doses. The aim of this study was to describe the incidence and risk factors of CIV in children who received multiple-day cisplatin chemotherapy. A total of 24 consecutive pediatric patients (age 0-19 years) who received multiple-day cisplatin chemotherapy in our hospital were enrolled. Patients with relapsed disease or primary intracranial tumor and those who received concurrent radiation therapy were excluded. The number of chemotherapy cycles reviewed was 107, with a median of five per patient. All patients received granisetron. Dexamethasone and NK-1 receptor antagonists (NK1RA) were used as additional antiemetics for prophylaxis of CIV. CIV was observed in 22 of 24 (92%) patients, and 61 of 107 (57%) cycles. Patients who developed CIV had a higher incidence of other chemotherapy-related adverse events (87 vs. 41%, P < 0.001). The incidence of CIV was lower in patients administered with NK1RA than those without (32 vs. 68%, P < 0.001). Multivariate logistic regression identified age less than or equal to 2 years (odds ratio [OR] = 0.25, 95% confidence interval [CI] = 0.10-0.63) and administration of NK1RA (OR = 0.16, 95% CI = 0.06-0.43) as independent factors for CIV. These results suggest that NK1RA is crucial to reduce CIV in children who receive multiple-day cisplatin chemotherapy. © 2017 Wiley Periodicals, Inc.

  2. Comparison of cisplatin- and carboplatin-based third-generation chemotherapy in 1,014 Chinese patients with advanced non-small-cell lung cancer.

    PubMed

    Luo, Jie; Leaw, Shiang J; Xu, Ying; Zheng, Di

    2011-12-01

    The outcome of patients with stage IIIB/IV non-small-cell lung cancer treated with platinum-based chemotherapy as first-line therapy was investigated to determine if cisplatin- or carboplatin-based combination therapy have similar efficacy by comparing the overall survival and safety profile for each combination regimen. A total of 1,014 patients, treated for stage IIIB and IV NSCLC between January 2002 and December 2008, with initial ECOG performance status of 0 and 1, adequate hematologic, hepatic, and renal function, who received at least two cycles of third-generation platinum-based chemotherapy, survived greater than 90 days, and experienced death were included for survival and safety analysis. Of them, 788 patients received cisplatin-based chemotherapy and 226 carboplatin-based. Cisplatin-based regimen yield significant better overall survival with a median survival time of 324 days compared to that of the carboplatin-based regimen of 286 days, attributable to the survival benefit of patients with stage III B (379 days vs. 283 days, Log-rank P=0.003), or with histology of squamous (308 days vs. 262 days, Log-rank P=0.01). Patients of the carboplatin-based arm were more likely to experience thrombocytopenia (OR=0.560, 95% CI=0.332-0.944, P=0.028), while cisplatin-based chemotherapy was associated with more nausea and vomiting (OR=3.720, 95% CI=1.971-7.021, P<0.0001). Non-small-cell lung cancer patients with stage IIIB disease and good performance status have a better survival advantage when treated with third-generation cisplatin-based chemotherapy compared to carboplatin-based regimen, and patients with squamous histology type may have experienced greater survival benefit than those with adenocarcinoma.

  3. The benefit of cisplatin-based polychemotherapy for adenocarcinoma of the lung. The Kyushu Lung Cancer Chemotherapy Study Group.

    PubMed

    Hara, N; Ohta, M; Ichikawa, Y; Kanda, T; Shima, K; Tamura, K; Hokama, M

    1990-01-01

    We studied the efficacy of cisplatin-based polychemotherapy for adenocarcinoma of the lung. A total of 136 patients were randomized for treatment with either cyclophosphamide, Adriamycin, cisplatin and mitomycin C (CAPM) or mitomycin C, cytosine arabinoside and tegafur (MCT). Radiation was given to the chests of patients at stage III. The differences in the response rate (35% in the CAPM arm and 13% in the MCT arm) were statistically significant (P less than 0.01). However, the significant difference was observed in stage-IV patients (CAPM, 33%; MCT, 4%; P less than 0.001) and not in stage-III patients (CAPM, 40%; MCT, 40%). The median period of survival was 9.5 months for the CAPM arm and 5.5 months for the MCT arm (P less than 0.035, Wilcoxon-Gehan test; P less than 0.1, log-rank test). Improved median survival for the CAPM regimen was demonstrated only by stage-IV patients (CAPM, 10 months; MCT, 5.5 months; P less than 0.025, Wilcoxon-Gehan test; P less than 0.05, log-rank test). The duration of the response, including PRs and NCs, was significantly different depending on the treatment, showing 5 months for the CAPM arm and 3 months for the MCT arm (P less than 0.05). The significant difference was also only observed in stage-IV patients. Myelosuppression was more severe with CAPM than with the MCT regimen. Nausea and vomiting were significantly increased in patients receiving the CAPM regimen. However, all toxicities were acceptable and there were no treatment-related deaths. We concluded that cisplatin-based chemotherapy, CAPM therapy, was of more benefit to patients with adenocarcinoma of the lung than MCT therapy.

  4. Pathological T0 Following Cisplatin-Based Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer: A Network Meta-analysis.

    PubMed

    Kim, Hyung Suk; Jeong, Chang Wook; Kwak, Cheol; Kim, Hyeon Hoe; Ku, Ja Hyeon

    2016-03-01

    To systematically assess and compare the relationship between various neoadjuvant chemotherapy regimens and pCR in patients with muscle-invasive bladder cancer. We performed a literature search of PubMed, Embase, and the Cochrane Library for all articles published before March 2015 and according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. There were 17 articles that met the study eligibility criteria and were selected for the final analysis. A direct pair-wise meta-analysis was performed for studies that compared the same regimen. Finally, a Bayesian network meta-analysis was used to indirectly compare the regimens. In a pair-wise meta-analysis, the methotrexate/vinblastine/Adriamycin/cisplatin [MVAC; OR, 4.36; 95% confidence interval (CI), 2.71-7.02] and gemcitabine/cisplatin (GC) regimens (OR, 4.92; 95% CI, 2.93-8.24) were significantly associated with a better pCR than RC alone. In a network meta-analysis, there was no significant difference in terms of pCR achievement between the GC and MVAC regimens (OR, 1.14; 95% CI; 0.85-1.70). However, in a subgroup network meta-analysis that only included prospective randomized trials, the MVAC regimen was significantly correlated with a higher rate of pCR (OR, 5.75; 95% CI, 1.96-24.18). The results of this meta-analysis suggest that a GC regimen was associated with a pCR rate that was similar to that of a MVAC regimen based on retrospective data, but only the MVAC regimen was proven to achieve pCR in prospective randomized trials. Additional prospective randomized trials comparing both regimens will be necessary to establish the optimal neoadjuvant chemotherapy regimen. ©2015 American Association for Cancer Research.

  5. Clinical outcomes following neoadjuvant cisplatin-based chemotherapy for bladder cancer in elderly compared with younger patients.

    PubMed

    Chau, C; Wheater, M; Geldart, T; Crabb, S J

    2015-03-01

    Bladder cancer is a disease of the elderly. Older patients might potentially be undertreated due to assumptions about benefit versus risk. Our objective was to determine outcomes in older patients receiving neoadjuvant chemotherapy for muscle-invasive bladder cancer (MIBC). We hypothesised that appropriately selected elderly patients (≥70 years) with MIBC could have similar clinical outcomes, and be safely treated, with standard neoadjuvant chemotherapy prior to definitive cystectomy or radiotherapy. We utilised a single institution case series analysis of patients with T2-4a N0 M0 transitional cell carcinoma of the bladder treated with cisplatin-based neoadjuvant chemotherapy between 2005 and 2011. Eighty-three patients were eligible. Median age was 68 (range 48-80), 33 patients (40%) were ≥70 years. Overall survival at 3 years was 65.8% (≥70) and 63.2% (<70) (P = 0.653), relapse-free survival at 3 years was 61.6% and 54.8% respectively (P = 0.471). The rates going forward to definitive local therapy (87.9% ≥ 70 and 84.0% < 70) and the pathological complete response rate (31.3% ≥ 70 and 40% < 70) were similar. Disease relapse rate was also similar (63.6% ≥ 70 vs. 60% < 70, P = 0.906). Elderly patients with good functional status and limited comorbidities diagnosed with MIBC receiving standard neoadjuvant chemotherapy followed by cystectomy or radiotherapy can have similar clinical outcomes as their younger counterparts. Prospective studies evaluating the optimum curative management in this elderly population are warranted.

  6. Abdominal visceral and subcutaneous fat increase, insulin resistance and hyperlipidemia in testicular cancer patients treated with cisplatin-based chemotherapy.

    PubMed

    Willemse, Peter-Paul M; van der Meer, Rutger W; Burggraaf, Jacobus; van Elderen, Saskia G C; de Kam, Marieke L; de Roos, Albert; Lamb, Hildo J; Osanto, Susanne

    2014-03-01

    Testicular cancer survivors treated with chemotherapy are at increased risk for metabolic syndrome (MetS) and cardiovascular disease (CVD). We explored acute effects of chemotherapy by assessing metabolic factors, abdominal fat volume, hepatic triglyceride content (HTC) and aortic wall stiffness. We studied 19 testicular cancer patients (age 20-54 years) before, at three and nine months after the start of chemotherapy. Blood serum was analyzed for lipids, glucose and insulin. Abdominal visceral and subcutaneous fat volume and aortic pulse wave velocity were assessed by magnetic resonance imaging (MRI) techniques; HTC was measured by proton MR spectroscopy. Three months after start of chemotherapy visceral abdominal fat volume had significantly increased from 202 ± 141 to 237 ± 153 ml (p = 0.009) whereas body mass index and subcutaneous fat volume significantly increased nine months after treatment from 24.4 ± 4.0 to 26.4 ± 4.1 kg/m(2) (p = 0.01) and from 556 ± 394 to 668 ± 460 ml (p = 0.002) respectively. Serum total cholesterol, low-density lipoprotein cholesterol and insulin also significantly increased three months after start of treatment from 4.88 ± 1.1 to 5.61 ± 1.50 mmol/l (p = 0.002), 3.31 ± 1.16 to 3.73 ± 1.41 mmol/l (p = 0.02) and 5.7 ± 4.4 to 9.6 ± 6.3 mU/ml (p = 0.03), respectively. Nine months after start of chemotherapy serum lipid and insulin concentrations had returned to baseline. HTC increased in seven of the 19 patients (36.8%) during follow-up. Aortic pulse wave velocity remained unchanged at the three time points measured. Cisplatin-based chemotherapy was associated with acute insulin resistance, dyslipidemia and an immediate increase in abdominal visceral adipose tissue and abdominal subcutaneous adipose tissue in testicular cancer patients. A large prospective cohort study with long follow-up is warranted to characterize the time course and relationship between acutely induced obesity and hypercholesterolemia and the development

  7. Challenges in management of patients with intracranial germ cell tumor and diabetes insipidus treated with cisplatin and/or ifosfamide based chemotherapy.

    PubMed

    Afzal, Samina; Wherrett, Diane; Bartels, Ute; Tabori, Uri; Huang, Annie; Stephens, Derek; Bouffet, Eric

    2010-05-01

    Patients with intracranial germ cell tumor (IGCT) often present with pituitary dysfunction, including diabetes insipidus (DI). Recent protocols have used pre-radiation chemotherapy with combinations of etoposide, carboplatin and/or cisplatin, and ifosfamide. Management of DI in these patients requires monitoring of electrolytes and fluids during chemotherapy and hyperhydration. All consecutive patients treated with chemotherapy for an IGCT during the period 1990-2007 at the Hospital for Sick Children, Toronto were reviewed. Out of 32 patients who received chemotherapy, 21 had DI. Only cycles containing cisplatin and/or ifosfamide and hyperhydration were considered. DI and non-DI patients were compared for each cycle of chemotherapy. Patients were studied for number of days in hospital per chemotherapy course, daily fluid input and output, changes in dose, schedule and route of administration of desmopressin (DDAVP) during chemotherapy, daily variations in sodium level, electrolyte monitoring requirements per day, and complications related to fluid and electrolyte disturbances. Fifty-four cycles of chemotherapy in DI patients were compared to 25 cycles in non DI patients. All 21 patients with DI required daily change in dosage and schedule of DDAVP. Marked variations in daily sodium level were observed in the DI group. Seventeen courses required prolonged admission in the DI group (one in non DI patients) and 6 patients experienced serious complications. In conclusion, DI is a risk factor for complications when cisplatin and/or ifosfamide based protocols are used. The role of these agents in the management of ICGT should be carefully evaluated and guidelines for management of DI established.

  8. Induction Cisplatin and Fluorouracil-Based Chemotherapy Followed by Concurrent Chemoradiation for Muscle-Invasive Bladder Cancer

    SciTech Connect

    Lin, C.-C.; Hsu, C.-H.; Cheng, Jason C.; Huang, C.-Y.; Tsai, Y.-C.; Hsu, F.-M.; Huang, K.-H.; Cheng, A.-L.; Pu, Y.-S.

    2009-10-01

    Purpose: To evaluate a multimodality bladder-preserving therapy in patients with muscle-invasive bladder cancer. Methods and Materials: Patients with stages T2-4aN0M0 bladder cancer suitable for cystectomy underwent radical transurethral resection and induction chemotherapy, followed by concurrent chemoradiotherapy (CCRT). Patients with a Karnofsky performance status (KPS) <80 or age {>=}70 years underwent Protocol A: induction chemotherapy with three cycles of the cisplatin and 5-fluorouracil (CF) regimen, and CCRT with six doses of weekly cisplatin and 64.8 Gy radiotherapy given with the shrinking-field technique. Patients with KPS {>=}80 and age <70 years underwent Protocol B: induction chemotherapy with three cycles of weekly paclitaxel plus the CF regimen, and CCRT with six doses of weekly paclitaxel and cisplatin plus 64.8 Gy radiotherapy. Interval cystoscopy was employed after induction chemotherapy and when radiotherapy reached 43.2 Gy. Patients without a complete response (CR) were referred for salvage cystectomy. Results: Among 30 patients (median, 66 years) enrolled, 17 and 13 patients underwent Protocol A and B, respectively. After induction chemotherapy, 23 patients achieved CR. Five (17%) of 7 patients without CR underwent salvage cystectomy. Overall, 28 patients (93%) completed the protocol treatment. Of 22 patients who completed CCRT, 1 had recurrence with carcinoma in situ and 3 had distant metastases. After a median follow-up of 47 months, overall and progression-free survival rate for all patients were 77% and 54% at 3 years, respectively. Of 19 surviving patients, 15 (79%) retained functioning bladders. Conclusions: Our protocols may be alternatives to cystectomy for selected patients who wish to preserve the bladder.

  9. Prevention of cisplatin-based chemotherapy-induced delayed nausea and vomiting using triple antiemetic regimens: a mixed treatment comparison

    PubMed Central

    Li, Hongjia; Le, Qiqi; Liu, Shanshan; Zong, Shaoqi; Zheng, Leizhen; Hou, Fenggang

    2016-01-01

    A variety of triple antiemetic regimens are being used to prevent cisplatin-based chemotherapy induced delayed emesis and nausea in cancer patients. We performed a network meta-analysis to compare the efficacies of the different regimens. Electronic searches of the PubMed, Cochrane Library and MEDLINE databases were performed to identify randomized controlled trials, and data were analyzed using JAGS, Stata 14.0 and R project. The primary outcome was a complete response (CR). The secondary outcomes were no vomiting (NV) and no nausea (NN). Among the 398 studies identified, 10 were eligible and included, providing data on nine regimens. In the CR analysis, the absolute rank of netupitant + palonosetron + dexamethasone (NEPA) was 0.8579. In the NV and NN analyses, NEPA's absolute ranks were 0.8631 and 0.7902, respectively. The compliance of patients treated with rolapitant + granisetron + dexamethasone (RGD) was the best due to a low incidence of adverse events, and good compliance was also observed with NEPA. It was difficult to achieve good compliance with aprepitant + granisetron + dexamethasone (AGD). Overall, NEPA was the best regimen, and aprepitant + ondansetron + dexamethasone (AOD) is also worthy of recommendation because of its low cost and good effect. For patients with severe constipation, hiccups, asthenia and/or delayed nausea, RGD is worthy of consideration. PMID:27015550

  10. Prognostic Model for Predicting Survival of Patients With Metastatic Urothelial Cancer Treated With Cisplatin-Based Chemotherapy

    PubMed Central

    2013-01-01

    A prognostic model that predicts overall survival (OS) for metastatic urothelial cancer (MetUC) patients treated with cisplatin-based chemotherapy was developed, validated, and compared with a commonly used Memorial Sloan-Kettering Cancer Center (MSKCC) risk-score model. Data from 7 protocols that enrolled 308 patients with MetUC were pooled. An external multi-institutional dataset was used to validate the model. The primary measurement of predictive discrimination was Harrell’s c-index, computed with 95% confidence interval (CI). The final model included four pretreatment variables to predict OS: visceral metastases, albumin, performance status, and hemoglobin. The Harrell’s c-index was 0.67 for the four-variable model and 0.64 for the MSKCC risk-score model, with a prediction improvement for OS (the U statistic and its standard deviation were used to calculate the two-sided P = .002). In the validation cohort, the c-indices for the four-variable and the MSKCC risk-score models were 0.63 (95% CI = 0.56 to 0.69) and 0.58 (95% CI = 0.52 to 0.65), respectively, with superiority of the four-variable model compared with the MSKCC risk-score model for OS (the U statistic and its standard deviation were used to calculate the two-sided P = .02). PMID:23411591

  11. Prognostic factors in patients with metastatic germ cell tumors who experienced treatment failure with cisplatin-based first-line chemotherapy.

    PubMed

    Lorch, Anja; Beyer, Jörg; Bascoul-Mollevi, Caroline; Kramar, Andrew; Einhorn, Lawrence H; Necchi, Andrea; Massard, Christophe; De Giorgi, Ugo; Fléchon, Aude; Margolin, Kim A; Lotz, Jean-Pierre; Germa Lluch, Jose Ramon; Powles, Thomas; Kollmannsberger, Christian K

    2010-11-20

    To develop a prognostic model in patients with germ cell tumors (GCT) who experience treatment failure with cisplatin-based first-line chemotherapy. Data from 1,984 patients with GCT who progressed after at least three cisplatin-based cycles and were treated with cisplatin-based conventional-dose or carboplatin-based high-dose salvage chemotherapy was retrospectively collected from 38 centers/groups worldwide. One thousand five hundred ninety-four (80%) of 1,984 eligible patients were randomly divided into a training set of 1,067 patients (67%) and a validation set of 527 patients (33%). Seminomas were set aside for posthoc analyses. Primary end point was the 2-year progression-free survival after salvage treatment. Overall, 990 patients (62%) relapsed and 604 patients (38%) remained relapse free. Histology, primary tumor location, response, and progression-free interval after first-line treatment, as well as levels of alpha fetoprotein, human chorionic gonadotrophin, and the presence of liver, bone, or brain metastases at salvage were identified as independent prognostic variables and used to build a prognostic model in the training set. Survival rates in the training and validation set were very similar. The estimated 2-year progression-free survival rates in patients not included in the training set was 75% in very low risk, 51% in low risk, 40% in intermediate risk, 26% in high risk, and only 6% in very high-risk patients. Due to missing values in individual variables, 69 patients could not reliably be classified into one of these categories. Prognostic variables are important in patients with GCT who experienced treatment failure with cisplatin-based first-line chemotherapy and can be used to construct a prognostic model to guide salvage strategies.

  12. An Epigenomic Approach to Improving Response to Neoadjuvant Cisplatin Chemotherapy in Bladder Cancer.

    PubMed

    Xylinas, Evanguelos; Hassler, Melanie R; Zhuang, Dazhong; Krzywinski, Martin; Erdem, Zeynep; Robinson, Brian D; Elemento, Olivier; Clozel, Thomas; Shariat, Shahrokh F

    2016-09-02

    Bladder cancer is among the five most common cancers diagnosed in the Western world and causes significant mortality and morbidity rates in affected patients. Therapeutic options to treat the disease in advanced muscle-invasive bladder cancer (MIBC) include cystectomy and chemotherapy. Neoadjuvant cisplatin-based combination chemotherapy is effective in MIBC; however, it has not been widely adopted by the community. One reason is that many patients do not respond to neoadjuvant chemotherapy, and no biomarker currently exists to identify these patients. It is also not clear whether a strategy to sensitize chemoresistant patients may exist. We sought to identify cisplatin-resistance patterns in preclinical models of bladder cancer, and test whether treatment with the epigenetic modifier decitabine is able to sensitize cisplatin-resistant bladder cancer cell lines. Using a screening approach in cisplatin-resistant bladder cancer cell lines, we identified dysregulated genes by RNA sequencing (RNAseq) and DNA methylation assays. DNA methylation analysis of tumors from 18 patients receiving cisplatin-based chemotherapy was used to confirm in vitro results. Cisplatin-resistant bladder cancer cells were treated with decitabine to investigate epigenetic sensitization of resistant cell lines. Our results show that HOXA9 promoter methylation status is associated with response to cisplatin-based chemotherapy in bladder cancer cell lines and in metastatic bladder cancer. Bladder cancer cells resistant to cisplatin chemotherapy can be sensitized to cisplatin by the DNA methylation inhibitor decitabine. Our data suggest that HOXA9 promoter methylation could serve as potential predictive biomarker and decitabine might sensitize resistant tumors in patients receiving cisplatin-based chemotherapy.

  13. Significance of TP53 mutations as predictive markers of adjuvant cisplatin-based chemotherapy in completely resected non-small-cell lung cancer.

    PubMed

    Ma, Xiaoli; Rousseau, Vanessa; Sun, Haiji; Lantuejoul, Sylvie; Filipits, Martin; Pirker, Robert; Popper, Helmut; Mendiboure, Jean; Vataire, Anne-Lise; Le Chevalier, Thierry; Soria, Jean Charles; Brambilla, Elisabeth; Dunant, Ariane; Hainaut, Pierre

    2014-05-01

    Adjuvant cisplatin-based chemotherapy only marginally improves survival in patients with completely resected non-small-cell lung cancer (NSCLC). We have evaluated the predictive value of mutations in TP53, encoding the tumour suppressor p53, in the International Adjuvant Lung Cancer Trial (IALT), a randomized trial of adjuvant cisplatin-based chemotherapy against observation. TP53 (exons 4-8) was sequenced in 524 archived specimens of IALT patients with a median follow-up of 7.5 years. Predictive analyses were based on Cox models adjusted for clinical and pathological variables. P-values ≤ 0.01 were considered as significant. Mutations were detected in 221 patients (42%) and had no predictive value for the effect of chemotherapy (interaction between TP53 and treatment: p = 0.17 for Overall Survival (OS); p = 0.06 for Disease-Free Interval, (DFS)). However, among patients with mutations, outcome appeared worse in treatment compared to observation arms (HR for OS = 1.36 (95% CI [0.97-1.31), p = 0.08; DFS = 1.40 (95% CI [1.01-1.95]), p = 0.04). When grouping mutations into classes according to predicted effects on protein structure, the tendency towards worse outcomes was restricted to "structure" mutations affecting residues of the hydrophobic core that are not located at the p53 protein-DNA interface (HR for death in this class vs wild-type T53 = 1.66; 95% CI [1.10-2.52], p = 0.02). Overall, TP53 mutations are not significant predictors of outcome in this trial of cisplatin-based chemotherapy, although a specific class of structural mutations may be associated with a tendency towards worse outcomes upon treatment. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  14. Multi-Institutional Assessment of Adverse Health Outcomes Among North American Testicular Cancer Survivors After Modern Cisplatin-Based Chemotherapy.

    PubMed

    Fung, Chunkit; Sesso, Howard D; Williams, Annalynn M; Kerns, Sarah L; Monahan, Patrick; Abu Zaid, Mohammad; Feldman, Darren R; Hamilton, Robert J; Vaughn, David J; Beard, Clair J; Kollmannsberger, Christian K; Cook, Ryan; Althouse, Sandra; Ardeshir-Rouhani-Fard, Shirin; Lipshultz, Steve E; Einhorn, Lawrence H; Fossa, Sophie D; Travis, Lois B

    2017-04-10

    Purpose To provide new information on adverse health outcomes (AHOs) in testicular cancer survivors (TCSs) after four cycles of etoposide and cisplatin (EPX4) or three or four cycles of bleomycin, etoposide, cisplatin (BEPX3/BEPX4). Methods Nine hundred fifty-two TCSs > 1 year postchemotherapy underwent physical examination and completed a questionnaire. Multinomial logistic regression estimated AHOs odds ratios (ORs) in relation to age, cumulative cisplatin and/or bleomycin dose, time since chemotherapy, sociodemographic factors, and health behaviors. Results Median age at evaluation was 37 years; median time since chemotherapy was 4.3 years. Chemotherapy consisted largely of BEPX3 (38.2%), EPX4 (30.9%), and BEPX4 (17.9%). None, one to two, three to four, or five or more AHOs were reported by 20.4%, 42.0%, 25.1%, and 12.5% of TCSs, respectively. Median number after EPX4 or BEPX3 was two (range, zero to nine and zero to 11, respectively; P > .05) and two (range, zero to 10) after BEPX4. When comparing individual AHOs for EPX4 versus BEPX3, Raynaud phenomenon (11.6% v 21.4%; P < .01), peripheral neuropathy (29.2% v 21.4%; P = .02), and obesity (25.5% v 33.0%; P = .04) differed. Larger cumulative bleomycin doses (OR, 1.44 per 90,000 IU) were significantly associated with five or more AHOs. Increasing age was a significant risk factor for one to two, three to four, or five or more AHOs versus zero AHOs (OR, 1.22, 1.50, and 1.87 per 5 years, respectively; P < .01); vigorous physical activity was protective (OR, 0.62, 0.51, and 0.41, respectively; P < .05). Significant risk factors for three to four and five or more AHOs included current (OR, 3.05 and 3.73) or former (OR, 1.61 and 1.76) smoking ( P < .05). Self-reported health was excellent/very good in 59.9% of TCSs but decreased as AHOs increased ( P < .001). Conclusion Numbers of AHOs after EPX4 or BEPX3 appear similar, with median follow-up of 4.3 years. A healthy lifestyle was associated with reduced number of AHOs.

  15. Breast cancer resistance protein (BCRP) and excision repair cross complement-1 (ERCC1) expression in esophageal cancers and response to cisplatin and irinotecan based chemotherapy

    PubMed Central

    Bharthuar, Anubha; Black, Jennifer D.; Levea, Charles; Malhotra, Usha; Mashtare, Terry L.; Iyer, Renuka

    2014-01-01

    Background Esophageal cancer patients face a dismal outcome despite tri-modality management and median survival remains 15-18 months. Breast cancer resistance protein (BCRP) is an ATP-dependent efflux protein associated with chemotherapy resistance. The role of BCRP expression in esophageal cancer and normal esophageal cells is not known. Excision repair cross complement-1 (ERCC1) overexpression has been correlated with poorer response to cisplatin based chemotherapy. We examined the expression of BCRP and ERCC1 in patients with esophageal cancer and correlated it with survival in patients receiving irinotecan and cisplatin based chemotherapy. Methods With IRB approval, 40 cases of esophageal cancer diagnosed from 2004-2008, were stained for BCRP and ERCC1 expression by immunohistochemistry and scored by a pathologist blinded to clinical data. Baseline demographics, therapy given and survival data were collected and correlated with BCRP and ERCC1 expression. Fisher’s exact test was used to determine association between BCRP and ERCC1 expression and demographics. Cox proportional hazards model was used for association of BCRP and ERCC1 with survival. Results On immunohistochemistry, 30/40 cancers (75%) expressed BCRP. Interestingly, down-regulation of BCRP expression in tumor compared with normal cells was seen in 40% of patients. ERCC1 positivity was seen in 15/30 cases (50%). Median overall survival (OS) was 19 months with no difference in survival between BCRP positive and negative patients (P=0.13) or ERCC1 positive and negative patients (P=0.85). Estimated hazard ratio (HR) of death for BRCP positive patients was 2.29 (95% CI: 0.79-6.64) and for ERCC1 positive patients was 1.09 (95% CI: 0.46-2.56). There was no association of BCRP and ERCC1 expression with disease stage, age, gender or histology. For patients who received cisplatin and irinotecan as first line chemotherapy, there was no difference in survival based on BCRP or ERCC1 status. Conclusions BCRP

  16. Changes in taste and smell function, dietary intake, food preference, and body composition in testicular cancer patients treated with cisplatin-based chemotherapy.

    PubMed

    IJpma, Irene; Renken, Remco J; Gietema, Jourik A; Slart, Riemer H J A; Mensink, Manon G J; Lefrandt, Joop D; Ter Horst, Gert J; Reyners, Anna K L

    2016-10-27

    Taste and smell changes due to chemotherapy may contribute to the high prevalence of overweight in testicular cancer patients (TCPs). This study investigates the taste and smell function, dietary intake, food preference, and body composition in TCPs before, during, and up to 1 year after cisplatin-based chemotherapy. Twenty-one consecutive TCPs participated. At baseline TCPs were compared to healthy controls (N = 48). Taste strips and 'Sniffin' Sticks' were used to determine psychophysical taste and smell function. Subjective taste, smell, appetite, and hunger were assessed using a questionnaire. Dietary intake was analyzed using a food frequency questionnaire. Food preference was assessed using food pictures varying in taste (sweet/savoury) and fat or protein content. A Dual-Energy X-ray Absorptiometry (DEXA) scan was performed to measure whole body composition. Compared to controls, TCPs had a lower smell threshold (P = 0.045) and lower preference for high fat sweet foods at baseline (P = 0.024). Over time, intra-individual psychophysical taste and smell function was highly variable. The salty taste threshold increased at completion of chemotherapy compared to baseline (P = 0.006). A transient decrease of subjective taste, appetite, and hunger feelings was observed per chemotherapy cycle. The percentage of fat mass increased during chemotherapy compared to baseline, while the lean mass and bone density decreased (P < 0.05). Coping strategies regarding subjective taste impairment should especially be provided during the first week of each chemotherapy cycle. Since the body composition of TCPs already had changed at completion of chemotherapy, intervention strategies to limit the impact of cardiovascular risk factors should probably start during treatment. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  17. Addition of 3-day aprepitant to ondansetron and dexamethasone for prophylaxis of chemotherapy-induced nausea and vomiting among patients with diffuse large B cell lymphoma receiving 5-day cisplatin-based chemotherapy.

    PubMed

    Abdel-Malek, Raafat; Abbas, Noha; Shohdy, Kyrillus S; Ismail, Mohamed; Fawzy, Radwa; Salem, Dalal S; Safwat, Ezzat

    2017-09-01

    Neurokinin-1 receptor antagonists, such as aprepitant are currently emerging as powerful prophylactic agents for chemotherapy-induced nausea and vomiting (CINV). Therefore, it is important to adjust the anti-emetic regimens based on personal risk factors of the patient, duration of the chemotherapy regimen and cost-effectiveness. To determine the efficacy of the 3-day aprepitant along with ondansetron and dexamethasone in controlling CINV in patients with large B cell lymphoma receiving multiday-cisplatin regimen chemotherapy. This is a pilot prospective cross-over trial. Patients were allocated to either aprepitant 125mg on day 1 and 80mg on days 2 & 3 or placebo in the first 2 cycles, with crossover to the opposite treatment in the 3rd and 4th cycles. The primary end point was complete response (CR) of both acute (days 1-5) and delayed (days 6-8) CINV. CR means neither to develop emetic episodes nor to use rescue anti-emetics medication. Twelve of the 15 patients recruited for the study were fully evaluable and completed 4 cycles of ESHAP regimen with a total of 48 cycles given. In the cycles with aprepitant and those without the CR were 83.3% and 0% respectively (p<0.05). Patients receiving aprepitant in the first 2 cycles recorded less nausea in subsequent cycles that were given without aprepitant. This was not statistically significant. This triple anti-emetic regimen showed efficacy in controlling the multi-day cisplatin-induced nausea and vomiting. Further randomized controlled trials are needed to compare between 3-day and 7-day aprepitant for multi-day cisplatin regimens. Copyright © 2017. Production and hosting by Elsevier B.V.

  18. The efficacy of irinotecan, paclitaxel, and oxaliplatin (IPO) in relapsed germ cell tumours with high-dose chemotherapy as consolidation: a non-cisplatin-based induction approach.

    PubMed

    Badreldin, Waleed; Krell, Jonathan; Chowdhury, Simon; Harland, Stephen J; Mazhar, Danish; Harding, Victoria; Frampton, Adam E; Wilson, Peter; Berney, Daniel; Stebbing, Justin; Shamash, Jonathan

    2016-03-01

    To determine the outcome of an expanded cohort of patients with relapsed germ cell tumours (GCTs) treated with a salvage chemotherapy regimen consisting of irinotecan, paclitaxel and oxaliplatin (IPO) and assess the role of IPO as an alternative to standard cisplatin-based chemotherapy regimens in this setting. The results of 72 consecutive patients were reviewed retrospectively. IPO was used either as a second-line treatment (29 patients), of which 20 patients subsequently received high-dose chemotherapy (HDCT), or third-line (43), of which 32 patients proceeded to HDCT. The 2-year progression-free survival (PFS) and 3-year overall survival (OS) rates for the whole cohort were 30.2% (95% confidence interval [CI] 17.3-40.5%) and 33.4% (95% CI 20.1-43.8%), respectively. Complete remission was achieved in 3%, marker-negative partial response (PR) in 41%, marker-positive PR in 18%, stable disease in 17% and progressive disease in 20%. In the second-line setting, the 2-year PFS rate was 43.5% (95% CI 21.7-60.8%) and 3-year OS 49.1% (95% CI 24.2-65.1%). In the third-line setting, the 2-year PFS rate was 21.0% (95% CI 9.5-35.4%) and the 3-year OS rate was 23.9% (95% CI 11.7-38.2). According to the current international prognostic factor study group criteria for first relapse for the high- and very high-risk group the 2-year PFS rates were 50% and 30%, respectively. There were two treatment-related deaths from IPO, and four from HDCT. Grade 3 or 4 toxicities included neutropenia (35%), thrombocytopaenia (18%), infection (15%), diarrhoea (11%) and lethargy (8%). IPO offers an effective, well-tolerated, non-nephrotoxic alternative to cisplatin-based salvage regimens for patients with relapsed GCTs. It appears particularly useful in high-risk patients and for those in whom cisplatin is ineffective or contra-indicated. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

  19. Taste and smell function in testicular cancer survivors treated with cisplatin-based chemotherapy in relation to dietary intake, food preference, and body composition.

    PubMed

    IJpma, Irene; Renken, Remco J; Gietema, Jourik A; Slart, Riemer H J A; Mensink, Manon G J; Lefrandt, Joop D; Ter Horst, Gert J; Reyners, Anna K L

    2016-10-01

    Chemotherapy can affect taste and smell function. This may contribute to the high prevalence of overweight and metabolic syndrome in testicular cancer survivors (TCS). Aims of the study were to evaluate taste and smell function and possible consequences for dietary intake, food preference, and body composition in TCS treated with cisplatin-based chemotherapy. Fifty TCS, 1-7 years post-chemotherapy, and 50 age-matched healthy men participated. Taste and smell function were measured using taste strips and 'Sniffin' Sticks', respectively. Dietary intake was investigated using a food frequency questionnaire. Food preference was assessed using food pictures varying in taste (sweet/savoury) and fat or protein content. Dual-Energy X-ray Absorptiometry was performed to measure body composition. Presence of metabolic syndrome and hypogonadism were assessed. TCS had a lower total taste function, a higher bitter taste threshold, higher Body Mass Index (BMI), and more (abdominal) fat than controls (p < 0.05). No differences in smell function and dietary intake were found. Testosterone level was an important determinant of body composition in TCS (p = 0.016). Although taste function was impaired in TCS, this was not related to a different dietary intake compared to controls. Lower testosterone levels were associated with a higher BMI, fat mass, and abdominal fat distribution in TCS. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Efficacy and safety of oral palonosetron compared with IV palonosetron administered with dexamethasone for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with solid tumors receiving cisplatin-based highly emetogenic chemotherapy (HEC).

    PubMed

    Karthaus, Meinolf; Tibor, Csőszi; Lorusso, Vito; Singh-Arora, Rajender; Filippov, Alexander; Rizzi, Giada; Borroni, Maria Elisa; Rossi, Giorgia; Grunberg, Steven M

    2015-10-01

    This study aims to compare the efficacy and safety of oral palonosetron with intravenous (IV) palonosetron for the prevention of cisplatin-related chemotherapy-induced nausea and vomiting (CINV). A multinational, randomized, double-blind study enrolling adult chemotherapy-naive patients with malignant solid tumors scheduled to receive cisplatin-based highly emetogenic chemotherapy (HEC). Patients received oral palonosetron (0.50 mg) or IV palonosetron (0.25 mg), each with oral dexamethasone. The primary objective was to demonstrate non-inferiority in terms of patients with a complete response (CR, no emesis/no rescue medication) within the acute phase (0-24 h after chemotherapy administration). Of the 743 patients randomized, 739 received study medications and 738 were included in the full analysis set. The CR rate in the acute phase was high for both groups (oral 89.4 %; IV 86.2 %). As this difference in proportions (stratum-adjusted Cochran-Mantel-Haenszel method) was 3.21 % (99 % confidence interval (CI) -2.74 to 9.17 %), non-inferiority was demonstrated (since the lower limit of the 99 % CI was closer to zero than the predefined margin of 15 %). Treatment-emergent adverse events (TEAEs) related to the study drug were rare (oral 3.2 %; IV 6.5 %). No TEAEs related to study drug leading to discontinuation were reported. Non-inferiority of oral versus IV palonosetron was demonstrated. The CR rate in the acute phase was >86 % in both patient groups. The safety profiles were comparable.

  1. Randomized Clinical Trial of Weekly vs. Triweekly Cisplatin-Based Chemotherapy Concurrent With Radiotherapy in the Treatment of Locally Advanced Cervical Cancer

    SciTech Connect

    Ryu, Sang-Young; Lee, Won-Moo; Kim, Kidong; Park, Sang-Il; Kim, Beob-Jong; Kim, Moon-Hong; Choi, Seok-Cheol; Cho, Chul-Koo; Nam, Byung-Ho; Lee, Eui-Don

    2011-11-15

    Purpose: To compare compliance, toxicity, and outcome of weekly and triweekly cisplatin administration concurrent with radiotherapy in locally advanced cervical cancer. Methods and Materials: In this open-label, randomized trial, 104 patients with histologically proven Stage IIB-IVA cervical cancer were randomly assigned by a computer-generated procedure to weekly (weekly cisplatin 40 mg/m{sup 2}, six cycles) and triweekly (cisplatin 75 mg/m{sup 2} every 3 weeks, three cycles) chemotherapy arms during concurrent radiotherapy. The difference of compliance and the toxicity profiles between the two arms were investigated, and the overall survival rate was analyzed after 5 years. Results: All patients tolerated both treatments very well, with a high completion rate of scheduled chemotherapy cycles. There was no statistically significant difference in compliance between the two arms (86.3% in the weekly arm, 92.5% in the triweekly arm, p > 0.05). Grade 3-4 neutropenia was more frequent in the weekly arm (39.2%) than in the triweekly arm (22.6%) (p = 0.03). The overall 5-year survival rate was significantly higher in the triweekly arm (88.7%) than in the weekly arm (66.5%) (hazard ratio 0.375; 95% confidence interval 0.154-0.914; p = 0.03). Conclusions: Triweekly cisplatin 75-mg/m{sup 2} chemotherapy concurrent with radiotherapy is more effective and feasible than the conventional weekly cisplatin 40-mg/m{sup 2} regimen and may be a strong candidate for the optimal cisplatin dose and dosing schedule in the treatment of locally advanced cervical cancer.

  2. Human antigen R as a predictive marker for response to gemcitabine-based chemotherapy in advanced cisplatin-resistant urothelial cancer

    PubMed Central

    Miyata, Yasuyoshi; Mitsunari, Kensuke; Akihiro, Asai; Watanabe, Shin-Ichi; Matsuo, Tomohiro; Ohba, Kojiro; Sakai, Hideki

    2017-01-01

    In patients with advanced urothelial cancer (UC), a combination of cisplatin (CDDP) and gemcitabine (GEM) is the most commonly used first-line systematic chemotherapy regimen. Although no standard regime for the treatment of CDDP-resistant UC has been established, GEM-based regimens are frequently used in these patients. In other types of cancer, human antigen R (HuR) status in cancer cells is closely associated with patient response to GEM. The aim of the present study was to establish the predictive potential of HuR expression for disease progression and survival in patients with UC who were treated with GEM-based regimens as a first or second-line chemotherapy. A total of 50 patients with advanced UC were enrolled in the current study. As first-line chemotherapy, methotrexate, vinblastine, epirubicin and CDDP (MVEC) combination therapy and GEM and CDDP combination therapy were administered in 34 (68.0%) and 16 patients (32.0%), respectively. Following progression, 45 patients (90.0%) were treated with combined GEM and paclitaxel therapy, and 5 patients (10.0%) were treated with GEM monotherapy. Cytoplasmic and nuclear HuR expression was evaluated using immunohistochemical techniques. The associations between HuR expression levels and local tumor response and treatment outcomes were analyzed. In first-line chemotherapy, no anticancer effects were observed to be significantly associated with nuclear or cytoplasmic HuR expression. In second-line chemotherapy nuclear HuR expression also exhibited no significant association with anticancer effects; however, the local tumor response was significantly improved if positive cytoplasmic HuR expression was present (P=0.002). Multivariate analyses revealed that cytoplasmic HuR expression levels were a significant predictive marker for longer OS (hazard ratio, 0.22; 95% confidence interval, 0.09–0.56; P=0.001). No significant association was observed between nuclear HuR expression levels and the overall survival. Therefore

  3. Comprehensive Audiometric Analysis of Hearing Impairment and Tinnitus After Cisplatin-Based Chemotherapy in Survivors of Adult-Onset Cancer

    PubMed Central

    Frisina, Robert D.; Wheeler, Heather E.; Fossa, Sophie D.; Kerns, Sarah L.; Fung, Chunkit; Sesso, Howard D.; Monahan, Patrick O.; Feldman, Darren R.; Hamilton, Robert; Vaughn, David J.; Beard, Clair J.; Budnick, Amy; Johnson, Eileen M.; Ardeshir-Rouhani-Fard, Shirin; Lipshultz, Steven E.; Dolan, M. Eileen; Travis, Lois B.

    2016-01-01

    Purpose Cisplatin is widely used but highly ototoxic. Effects of cumulative cisplatin dose on hearing loss have not been comprehensively evaluated in survivors of adult-onset cancer. Patients and Methods Comprehensive audiological measures were conducted on 488 North American male germ cell tumor (GCT) survivors in relation to cumulative cisplatin dose, including audiograms (0.25 to 12 kHz), tests of middle ear function, and tinnitus. American Speech-Language-Hearing Association criteria defined hearing loss severity. The geometric mean of hearing thresholds (0.25 to 12 kHz) summarized overall hearing status consistent with audiometric guidelines. Patients were sorted into quartiles of hearing thresholds of age- and sex-matched controls. Results Increasing cumulative cisplatin dose (median, 400 mg/m2; range, 200 to 800 mg/m2) was significantly related to hearing loss at 4, 6, 8, 10, and 12 kHz (P trends, .021 to < .001): every 100 mg/m2 increase resulted in a 3.2-dB impairment in age-adjusted overall hearing threshold (4 to 12 kHz; P < .001). Cumulative cisplatin doses > 300 mg/m2 were associated with greater American Speech-Language-Hearing Association–defined hearing loss severity (odds ratio, 1.59; P = .0066) and worse normative-matched quartiles (odds ratio, 1.33; P = .093) compared with smaller doses. Almost one in five (18%) patients had severe to profound hearing loss. Tinnitus (40% patients) was significantly correlated with reduced hearing at each frequency (P < .001). Noise-induced damage (10% patients) was unaffected by cisplatin dose (P = .59). Hypertension was significantly related (P = .0066) to overall hearing threshold (4 to 12 kHz) in age- and cisplatin dose–adjusted analyses. Middle ear deficits occurred in 22.3% of patients but, as expected, were not related to cytotoxic drug dosage. Conclusion Follow-up of adult-onset cancer survivors given cisplatin should include routine inquiry for hearing status and tinnitus, referral to audiologists

  4. Comparison of the Efficacy between Gemcitabine-Cisplatin and Capecitabine-Cisplatin Combination Chemotherapy for Advanced Biliary Tract Cancer

    PubMed Central

    Lee, Jieun; Hong, Tae Ho; Lee, In Seok; You, Young Kyoung; Lee, Myung Ah

    2015-01-01

    Purpose Gemcitabine-cisplatin combination chemotherapy has been regarded as standard regimen for advanced or metastatic biliary tract cancer (BTC), based on the ABC-02 trial. To date, however, no studies have compared the efficacies of gemcitabine-platinum and fluoropyrimidine- platinum combination chemotherapy, even though fluoropyrimidine has been widely used as a backbone agent for gastrointestinal cancer. This study compared the efficacy and toxicities of gemcitabine-cisplatin (GP) and capecitabine-cisplatin (XP) combination chemotherapy for treatment of advanced BTC. Materials and Methods We examined 49 patients treated with GP and 44 patients treated with XP from October 2009 to July 2012. All patients had unresectable BTC. The GP regimen comprised gemcitabine (1,000 mg/m2, intravenously [IV], days 1 and 8) and cisplatin (75 mg/m2, IV, day 1). The XP regimen comprised capecitabine (1,250 mg/m2 twice a day, peroral, days 1-14) and cisplatin (60 mg/m2, IV, day 1, every three weeks). We analyzed the response rate (RR), time to progression (TTP), overall survival (OS), and toxicity. Results The RRs were 27.3% and 6.1% in the XP and GP arms, respectively. XP resulted in longer TTP (5.2 months vs. 3.6 months, p=0.016), but OS was not statistically different (10.7 months vs. 8.6 months, p=0.365). Both regimens resulted in grade 3-4 hematologic toxicities, but febrile neutropenia was not noted. Grade 3-4 asthenia, stomatitis, and hand-foot syndrome occurred more frequently in the XP arm. Conclusion XP resulted in a superior TTP and RR compared to GP for treatment of advanced BTC, with comparable toxicity. Conduct of prospective large, randomized trials to evaluate the possibility of XP as another standard therapy is warranted. PMID:25648099

  5. Comparison of the Efficacy between Gemcitabine-Cisplatin and Capecitabine-Cisplatin Combination Chemotherapy for Advanced Biliary Tract Cancer.

    PubMed

    Lee, Jieun; Hong, Tae Ho; Lee, In Seok; You, Young Kyoung; Lee, Myung Ah

    2015-04-01

    Gemcitabine-cisplatin combination chemotherapy has been regarded as standard regimen for advanced or metastatic biliary tract cancer (BTC), based on the ABC-02 trial. To date, however, no studies have compared the efficacies of gemcitabine-platinum and fluoropyrimidine- platinum combination chemotherapy, even though fluoropyrimidine has been widely used as a backbone agent for gastrointestinal cancer. This study compared the efficacy and toxicities of gemcitabine-cisplatin (GP) and capecitabine-cisplatin (XP) combination chemotherapy for treatment of advanced BTC. We examined 49 patients treated with GP and 44 patients treated with XP from October 2009 to July 2012. All patients had unresectable BTC. The GP regimen comprised gemcitabine (1,000 mg/m(2), intravenously [IV], days 1 and 8) and cisplatin (75 mg/m(2), IV, day 1). The XP regimen comprised capecitabine (1,250 mg/m(2) twice a day, peroral, days 1-14) and cisplatin (60 mg/m(2), IV, day 1, every three weeks). We analyzed the response rate (RR), time to progression (TTP), overall survival (OS), and toxicity. The RRs were 27.3% and 6.1% in the XP and GP arms, respectively. XP resulted in longer TTP (5.2 months vs. 3.6 months, p=0.016), but OS was not statistically different (10.7 months vs. 8.6 months, p=0.365). Both regimens resulted in grade 3-4 hematologic toxicities, but febrile neutropenia was not noted. Grade 3-4 asthenia, stomatitis, and hand-foot syndrome occurred more frequently in the XP arm. XP resulted in a superior TTP and RR compared to GP for treatment of advanced BTC, with comparable toxicity. Conduct of prospective large, randomized trials to evaluate the possibility of XP as another standard therapy is warranted.

  6. Combined chemotherapy and photodynamic therapy using a nanohybrid based on layered double hydroxides to conquer cisplatin resistance.

    PubMed

    Wang, Zhigang; Ma, Rong; Yan, Li; Chen, Xianfeng; Zhu, Guangyu

    2015-07-25

    A nanohybrid is assembled by ratiometrically co-loading Pt(IV) prodrugs and photosensitizers into layered double hydroxide nanoparticles. The nanohybrid shows synergistic cell-killing effects and is significantly active against the proliferation of cisplatin-resistant human cancer cells with nanomolar IC50 values. Profound mechanistic investigations confirm its action mode of combined chemo- and photodynamic therapy.

  7. Ifosfamide, Cisplatin or Carboplatin, and Etoposide (ICE)-based Chemotherapy for Mobilization of Autologous Peripheral Blood Stem Cells in Patients with Lymphomas

    PubMed Central

    Zhou, Ping; Liu, Peng; Zhou, Sheng-Yu; He, Xiao-Hui; Han, Xiao-Hong; Qin, Yan; Yang, Sheng; Zhang, Chang-Gong; Gui, Lin; Yao, Jia-Rui; Zhao, Li-Ya; Zhang, Shu-Xiang; Sun, Yan; Shi, Yuan-Kai

    2015-01-01

    Background: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a promising approach for lymphomas. This study aimed to evaluate the effect of ifosfamide, cisplatin or carboplatin, and etoposide (ICE)-based regimen as a mobilization regimen on relapsed, refractory, or high-risk aggressive lymphoma. Methods: From June 2001 to May 2013, patients with lymphomas who mobilized by ICE-based regimen for ASCT were analyzed in this retrospective study. The results of the autologous peripheral blood stem cells collection, toxicity, engraftment after ICE-based mobilization regimen were analyzed in this study. Furthermore, risk factors for overall survival (OS) and progression free survival (PFS) were evaluated by univariate analysis. Results: The stem cells were mobilized using ICE-based regimen plus rituximab or ICE-based regimen alone in 12 patients and 54 patients, respectively. The results of stem cell mobilization were excellent. Ninety-seven percentages of the patients had the stem cell collection of at least 2.0 × 106 CD34+ cells/kg and 68% had at least 5 × 106 CD34+ cells/kg. Fifty-eight percentage of the patients experienced Grade 4 neutropenia, 20% developed febrile neutropenia, and only 12% had Grade 4 thrombocytopenia. At a median follow-up of 63.8 months, the 5-year PFS and OS were 64.4% and 75.3%, respectively. Conclusion: ICE is a powerful regimen for stem cell mobilization in patients with lymphomas. PMID:26365969

  8. Cisplatin-based chemotherapy followed by focal, reduced-dose irradiation for pediatric primary central nervous system germinomas.

    PubMed

    Douglas, James G; Rockhill, Jason K; Olson, James M; Ellenbogen, Richard G; Geyer, J Russell

    2006-01-01

    The objective of this study was to evaluate retrospectively one institution's experience treating pediatric central nervous system (CNS) pure germinomas with platinum-based chemotherapy followed by focal, reduced-dose irradiation. Eight patients were identified with localized, pure CNS germinomas from 1993 to 2004 at the authors' institution. The median age at diagnosis was 13 years (range 7-19). The median follow-up was 40 months (range 8-141). The tumor location was suprasellar in four, the pineal region in three, and the third ventricle in one. Irradiation was started a median of 20 weeks (range 17-22) from diagnosis and consisted of conformal fields to the primary site as determined by the initial diagnostic MR plus a 1.5- to 2-cm margin. Six of the eight patients received a dose of 3,060 cGy; two patients received 3,600 cGy. The 5-year actuarial event free survival was 71% (56-86%, 95% CI). Two patients suffered marginal (at field edge) failures and both were salvaged using reinduction platinum-based chemotherapy followed by cranial spinal irradiation and a boost to the primary tumor. The 5-year actuarial overall survival was 100%. There were no spinal failures. These data suggest that a reduction in both volume and dose (30.6-36 Gy) retains the excellent survival rates for patients with localized, pure germinomas of the CNS. A higher rate of ventricular relapse rate is observed, although salvage of those patients is feasible.

  9. Magnetic nanoparticle hyperthermia enhancement of cisplatin chemotherapy cancer treatment

    PubMed Central

    Petryk, Alicia A.; Giustini, Andrew J.; Gottesman, Rachel E.; Kaufman, Peter A.; Hoopes, P. Jack

    2016-01-01

    Purpose The purpose of this study was to examine the therapeutic effect of magnetic nanoparticle hyperthermia (mNPH) combined with systemic cisplatin chemotherapy in a murine mammary adenocarcinoma model (MTGB). Materials and methods An alternating magnetic field (35.8 kA/m at 165 kHz) was used to activate 110 nm hydroxyethyl starch-coated magnetic nanoparticles (mNP) to a thermal dose of 60 min at 43 °C. Intratumoral mNP were delivered at 7.5 mg of Fe/cm3 of tumour (four equal tumour quadrants). Intraperitoneal cisplatin at 5 mg/kg body weight was administered 1 h prior to mNPH. Tumour regrowth delay time was used to assess the treatment efficacy. Results mNP hyperthermia, combined with cisplatin, was 1.7 times more effective than mNP hyperthermia alone and 1.4 times more effective than cisplatin alone (p<0.05). Conclusions Our results demonstrate that mNP hyperthermia can result in a safe and significant therapeutic enhancement for cisplatin cancer therapy. PMID:24144336

  10. Reappraisal of short-term low-volume hydration in cisplatin-based chemotherapy: results of a prospective feasibility study in advanced lung cancer in the Okayama Lung Cancer Study Group Trial 1002.

    PubMed

    Hotta, Katsuyuki; Takigawa, Nagio; Hisamoto-Sato, Akiko; Ichihara, Eiki; Kudo, Kenichiro; Uchida, Koji; Yanase-Nakamura, Kayo; Tanaka, Hisaaki; Kato, Yuka; Tabata, Masahiro; Tanimoto, Mitsune; Kiura, Katsuyuki

    2013-11-01

    Cisplatin can induce severe renal toxicity. However, the degree and pattern of hydration that is most efficient at preventing it have scarcely been formally evaluated. We here performed a prospective feasibility study of cisplatin-based chemotherapy with short-term low-volume hydration in advanced lung cancer. Chemo-naïve patients with advanced lung cancer and reserving renal function who were suitable for cisplatin use (≥60 mg/m(2) on Day 1) were eligible for this study. Two-and-a-half-liter hydration within ∼4.5 h was investigated. The primary end point was the proportion of patients who underwent cisplatin-based chemotherapy without any Grade 2 or more renal toxicity in the first cycle. A total of 46 patients were registered, all of whom were evaluable for renal toxicity. The median baseline creatinine score was 0.70 mg/dl and the median cisplatin dose on Day 1 was 80 mg/m(2). In the first cycle, none of the patients developed Grade 2 or more creatinine toxicity, which met the primary endpoint. Four patients (9%) had Grade 1 toxicity, with a median worst creatinine score of 1.19 mg/dl, but it disappeared rapidly. Creatinine toxicity was influenced by several clinical factors, including the performance status. Ten patients (22%) needed extra hydration during the first cycle, mainly due to gastrointestinal toxicity. However, all 10 were able to undergo further cycles of treatment. Thirty-two (86%) of the 37 patients who were assumed to be able to undergo further treatment at our institute received it in an outpatient setting. This study demonstrated prospectively the feasibility of short-term low-volume hydration.

  11. Quantitation of cis-diamminedichloroplatinum II (cisplatin)-DNA-intrastrand adducts in testicular and ovarian cancer patients receiving cisplatin chemotherapy.

    PubMed

    Reed, E; Yuspa, S H; Zwelling, L A; Ozols, R F; Poirier, M C

    1986-02-01

    The antitumor activity of cis-diamminedichloroplatinum II (cisplatin) is believed to be related to its covalent interaction with DNA where a major DNA binding product is an intrastrand N7-bidentate adduct on adjacent deoxyguanosines. A novel immunoassay was used to quantitate this adduct in buffy coat DNA from testicular and ovarian cancer patients undergoing cisplatin therapy. 44 out of 120 samples taken from 45 cisplatin patients had detectable cisplatin-DNA adducts. No adducts were detected in 18 samples of DNA taken from normal controls, patients on other chemotherapy, or patients before treatment. The quantity of measurable adducts increased as a function of cumulative dose of cisplatin. This was observed both during repeated daily infusion of the drug and over long-term, repeated 21-28 d cycles of administration. These results suggested that adduct removal is slow even though the tissue has a relatively rapid turnover. Patients receiving cisplatin for the first time on 56-d cycles, and those given high doses of cisplatin as a "salvage" regimen, did not accumulate adducts as rapidly as patients on first time chemotherapy on 21- or 28-d cycles. Disease response data, evaluated for 33 cisplatin-treated patients, showed a positive correlation between the formation of DNA adducts and response to drug therapy. However, more data will be required to confirm this relationship. These data show that specific immunological probes can readily be applied to quantitate DNA adducts in patients undergoing cancer chemotherapy.

  12. Short hydration in chemotherapy containing cisplatin (≥75 mg/m2) for patients with lung cancer: a prospective study.

    PubMed

    Horinouchi, Hidehito; Kubota, Kaoru; Itani, Hidetoshi; Taniyama, Tomoko Katsui; Nakamichi, Shinji; Wakui, Hiroshi; Kanda, Shintaro; Nokihara, Hiroshi; Yamamoto, Noboru; Sekine, Ikuo; Tamura, Tomohide

    2013-11-01

    We previously reported that 22% of lung cancer patients experienced a Grade 2 or 3 elevation in creatinine after chemotherapy containing cisplatin. We conducted a Phase II trial to evaluate the safety and efficacy of short hydration. The major eligibility criteria included patients with lung cancer for whom a ≥75 mg/m(2) cisplatin-based regimen was indicated and adequate organ function. Cisplatin was administered with pre- and post-hydration containing 10 mEq of potassium chloride in 500 ml of fluid over a 60-min period. Immediately before the administration of cisplatin, mannitol (20%, 200 ml) was administered as forced diuresis over 30 min. And magnesium sulfate (8 mEq) was added to pre-hydration. Forty-four patients were enrolled between April and December 2011. The patients included 29 men and 15 women with a median (range) age of 64 (42-74) years. Twenty patients received cisplatin and pemetrexed as their most frequent regimen and 38 patients received three to four cycles of chemotherapy. The median (range) duration and volume of the chemotherapies were 4.0 (3.3-6.8) h and 1600 (1550-2050) ml, respectively. Of the 44 patients, 43 (97.8%) completed the cisplatin-based chemotherapy without Grade 2 or higher renal dysfunction. The only patient who had Grade 2 elevation in creatinine (maximum value 1.7 mg/dl) had prompt improvement in creatinine levels and completed four cycles of chemotherapy. The short hydration is safe without severe renal toxicities in regimens containing cisplatin (≥75 mg/m(2)) for patients with lung cancer.

  13. Comparison between 5-day aprepitant and single-dose fosaprepitant meglumine for preventing nausea and vomiting induced by cisplatin-based chemotherapy.

    PubMed

    Ando, Yosuke; Hayashi, Takahiro; Ito, Kaori; Suzuki, Eri; Mine, Naoyuki; Miyamoto, Ayumi; Oya, Miyuki; Matsuda, Hidezo; Isaji, Ami; Nakanishi, Toru; Imaizumi, Kazuyoshi; Shibata, Tomoyuki; Okada, Tatsuyoshi; Sakurai, Kazuo; Naito, Kensei; Uyama, Ichiro; Kawada, Kenji; Takahashi, Hiroshi; Yamada, Shigeki

    2016-02-01

    We aimed to compare the preventive effect of 5-day administration of aprepitant with single administration of fosaprepitant meglumine against nausea and vomiting symptoms due to highly emetogenic chemotherapy regimens comprising cisplatin (CDDP). Subjects were inpatients who underwent chemotherapy for gastric cancer, esophageal cancer, lung cancer, or head and neck cancer with a regimen comprising 60 mg/m(2) or higher dose of CDDP. In this randomised, open-label, controlled study, the subjects were assigned to a group given aprepitant for 5 days or a group given a single administration of fosaprepitant meglumine. The nausea and vomiting symptoms that emerged within 7 days after the first CDDP administration were investigated with a questionnaire form; the results were compared between the two groups. Risk factors affecting nausea and vomiting symptoms were also investigated. Of the 101 patients enrolled, 93 patients were included (48 in the 5-day aprepitant group and 45 in the single fosaprepitant meglumine group). No significant intergroup differences in the complete response rate or the complete control rate were found over the entire period. The nausea score tended to increase from day 3 in both groups, but no significant intergroup difference was observed. Furthermore, the investigation of risk factors affecting moderate or severe nausea symptoms indicated that the fosaprepitant meglumine administration was not a risk factor. Single administration of fosaprepitant meglumine was not inferior to 5-day administration of aprepitant for preventing acute and delayed nausea and vomiting symptoms occurring after administration of CDDP (60 mg/m(2) or higher).

  14. Phase I trial of daily triapine in combination with cisplatin chemotherapy for advanced-stage malignancies.

    PubMed

    Kunos, Charles A; Chu, Edward; Beumer, Jan H; Sznol, Mario; Ivy, S Percy

    2017-01-01

    Advanced-stage malignancies have increased deoxyribonucleotide demands in DNA replication and repair, making deoxyribonucleotide supply a potential exploitable target for therapy based on ribonucleotide reductase (RNR) inhibition. A dose-finding phase I trial was conducted of intravenous (i.v.) triapine, a small-molecule RNR inhibitor, and cisplatin chemotherapy in patients with advanced-stage solid tumor malignancies. Patients received dose-finding levels of i.v. triapine (48-96 mg/m(2)) and i.v. cisplatin (20-75 mg/m(2)) on 1 of 3 different schedules. The primary endpoint was to identify the maximum tolerated dose of a triapine-cisplatin combination. Secondary endpoints included the rate of triapine-cisplatin objective response and the pharmacokinetics and bioavailability of a single oral triapine dose. (Clinicaltrials.gov number, NCT00024323). The MTD was 96 mg/m(2) triapine daily days 1-4 and 75 mg/m(2) cisplatin split over day 2 and day 3. Frequent grade 3 or 4 adverse events included fatigue, dyspnea, leukopenia, thrombocytopenia, and electrolyte abnormalities. No objective responses were observed; 5 (50%) of 10 patients treated at the MTD had stable disease. Pharmacokinetics indicated an oral triapine bioavailability of 88%. The triapine-cisplatin combination may be given safely in patients with advanced-stage solid tumor malignancies. On the basis of these results, a phase I trial adequately powered to evaluate oral triapine bioavailability in women with advanced-stage uterine cervix or vulvar cancers is underway.

  15. Feasibility of olanzapine, multi acting receptor targeted antipsychotic agent, for the prevention of emesis caused by continuous cisplatin- or ifosfamide-based chemotherapy.

    PubMed

    Bun, Seiko; Yonemori, Kan; Akagi, Toru; Noguchi, Emi; Shimoi, Tatsunori; Shimomura, Akihiko; Yunokawa, Mayu; Shimizu, Chikako; Fujiwara, Yasuhiro; Makino, Yoshinori; Hayashi, Yoshikazu; Tamura, Kenji

    2017-07-21

    Background To determine the feasibility and efficacy of olanzapine, which is approved by the Pharmaceuticals and Medical Devices Agency as multi acting receptor targeted antipsychotic agent of the thienobenzodiazepine class, for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients undergoing continuous five-day chemotherapy. Patients and methods This study was a prospective dose escalation study at a single center (UMIN ID: UMIN000015386). Patients received a combination of adriamycin and ifosfamide (AI) or a combination of bleomycin, etoposide, and cisplatin (BEP). On days 1-5, all patients received intravenous granisetron (1 mg) and intravenous dexamethasone sodium phosphate (24 mg). Olanzapine was administrated on day-1 to day5 at bedtime. The dose of olanzapine followed a dose-escalation scheme, with monitoring of safety and tolerability at each dose. A 3 + 3 cohort design was used, with three to six patients per cohort. Results Nine patients were enrolled (three for each cohort). No patients experienced dose-limiting toxicity (DLT). The most frequent adverse events were dry mouth and constipation. In each cohort, the maximum severity of nausea was Grade 2, and no patients experienced a vomiting episode. Conclusion A 2.5 mg/day dosage of olanzapine is sufficient to prevent from CINV in Japanese patients receiving continuous five-day chemotherapy. A dose of 10 mg/day, which is recommended by international CINV guidelines, is also tolerated. If CINV is not controlled by an initial dose of 2.5 mg/day of olanzapine, dosage escalation is encouraged. Future studies should compare olanzapine with aprepitant.

  16. Effect of vinorelbine, ifosfamide, and cisplatin combination chemotherapy in advanced non-small-cell lung cancer.

    PubMed

    Ahn, J B; Ko, W K; Lee, J G; Shim, K Y; Jeung, H C; Park, J O; Yoo, N C; Kim, B S; Kim, S K; Kim, S K; Kim, J H

    2000-12-01

    Cisplatin-based chemotherapy is being tried in the treatment of nonoperable cases of non-small-cell lung cancer (NSCLC). However, the prognosis is unfavorable and to improve survival, clinical studies using various combinations of a variety of drugs as well as experimental material are in progress. We compared the efficacy and toxicities of combination chemotherapy using different doses of vinorelbine and ifosfamide with a constant dose of cisplatin in this study. Patients diagnosed with inoperable stage III or IV NSCLC between June 1997 and December 1998 were included. Cisplatin was administered at a constant dose of 80 mg/m2 on day 5, whereas vinorelbine on days 1 and 5 and ifosfamide on day 5 were administered in one of two different doses. In arm A, vinorelbine 25 mg/m2 and ifosfamide 3.0 g/m2 were administered. In arm B, vinorelbine 20 mg/m2 and ifosfamide 2.5 g/m2 were administered. Also, we reviewed for phase II and III studies that test 1) cisplatin, 2) vinorelbine monotherapy, and 3) vinorelbine/cisplatin/ifosfamide combination chemotherapy for stage IIIb-IV non-SCLC. Summation dose intensity (SDI) was calculated in each published and current study. Twenty patients in arm A and 35 patients in arm B were available for evaluation. There was no difference in patient activity, pathologic diagnosis, and differentiation or stage between the two arms. The median number of cycles was four in both arms. The response rate was 50% in arm A and 30% in arm B. The median survival times for arm A and B were 40 and 42 weeks, respectively, whereas the SDI was 1.94 and 1.7, respectively. More than grade III leukopenia was observed in 28.9% in arm A, which is more frequent than the 17.2% in arm B. There was a significant correlation between the SDIs and response rates and median survival (r2 = 0.629, p = 0.001; r2 = 0.453, p = 0.001, respectively). Although the follow-up period is relatively short, the survival time was similar in both arms. Because a high response rate may

  17. Synergistic Cisplatin/Doxorubicin Combination Chemotherapy for Multidrug-Resistant Cancer via Polymeric Nanogels Targeting Delivery.

    PubMed

    Wu, Haiqiu; Jin, Haojie; Wang, Cun; Zhang, Zihao; Ruan, Haoyu; Sun, Luyan; Yang, Chen; Li, Yongjing; Qin, Wenxin; Wang, Changchun

    2017-03-08

    Combination chemotherapy has been proposed to achieve synergistic effect and minimize drug dose for cancer treatment in clinic application. In this article, the stimuli-responsive polymeric nanogels (<100 nm in size) based on poly(acrylic acid) were designed as codelivery system for doxorubicin and cisplatin to overcome drug resistance. By chelation, electrostatic interaction, and π-π stacking interactions, the nanogels could encapsulate doxorubicin and cisplatin with designed ratio and high capacity. Compared with free drugs, the nanogels could deliver more drugs into MCF-7/ADR cells. Significant accumulation in tumor tissues was observed in the biodistribution experiments. The in vitro antitumor studies demonstrated the superior cell-killing activity of the nanogel drug delivery system with a combination index of 0.84, which indicated the great synergistic effect. All the antitumor experimental data revealed that the combination therapy was effective for the multidrug-resistant MCF-7/ADR tumor with reduced side effects.

  18. Poly(amido)amine (PAMAM) dendrimer-cisplatin complexes for chemotherapy of cisplatin-resistant ovarian cancer cells

    NASA Astrophysics Data System (ADS)

    Yellepeddi, Venkata Kashyap; Vangara, Kiran Kumar; Palakurthi, Srinath

    2013-09-01

    Dendrimer-cisplatin complexes were prepared using PAMAM dendrimers with terminal -NH2 and -COOH groups as well as biotin-conjugated dendrimers. Preformulation parameters of dendrimer-cisplatin complexes were studied using differential scanning calorimetry (DSC) and inductively coupled plasma-mass spectrometry (ICP-MS). Cytotoxicity and mechanism of cytotoxicity of dendrimer-cisplatin complexes was investigated in OVCAR-3, SKOV, A2780 and cisplatin-resistant CP70 human ovarian cancer cell lines. The loading of cisplatin in dendrimers was 11 % (w/w). PAMAM G4 dendrimers with amine surface groups (biotinylated and native) have shown 2.5- to 3.0-fold reduction in IC50 values in ovarian cancer cells when compared with carboxylate surface dendrimers ( p < 0.05). A correlation was observed among cytotoxicity of the complexes, cellular uptake, and platinum-DNA adduct formation. Treatment with dendrimer-cisplatin complexes resulted in a 7.0-fold increase ( p < 0.05) in expression of apoptotic genes ( Bcl2, Bax, p53) and 13.2- to 27.1-fold increase ( p < 0.05) in the activity of caspases 3, 8, and 9 in vitro. Results suggest that PAMAM dendrimers can be used as potential carrier for cisplatin chemotherapy of ovarian cancer.

  19. Estimating glomerular filtration rate in oncology patients receiving Cisplatin chemotherapy: Predicted creatinine clearance against 99mTc-DTPA methods

    NASA Astrophysics Data System (ADS)

    Khaidah Syed Sahab, Sharifah; Manap, Mahayuddin; Hamzah, Fadzilah

    2017-05-01

    The therapeutic potential of cisplatin as the best anticancer treatment for solid tumor is limited by its potential nephrotoxicity. This study analyses the incidence of cisplatin induced nephrotoxicity in oncology patients through GFR estimation using 99mTc-DTPA plasma sampling (reference method) and to compare with predicted creatinine clearance and Tc-99m renal scintigraphy. A prospective study of 33 oncology patients referred for GFR estimation in Penang Hospital. The incidence of cisplatin induced nephrotoxicity was analysed via radionuclide and creatinine based method. Of 33 samples, only 21 selected for the study. The dose of cisplatin given was 75 mg/m2 for each cycle. The mean difference of GFR pre and post chemotherapy (PSC 2) was 13.38 (-4.60, 31.36) ml/min/1.73m2 (p 0.136). Of 21 patients, 3 developed severe nephrotoxicity (GFR < 50ml/min/1.73 m2) contributing 14.3% of incidence. Bland-Altman plot showed only PSC 1 is in agreement with PSC 2 technique. Intraclass Correlation Coefficients (ICC) also showed that PSC 1 has high degree of reliability in comparison to PSC 2 (p < 0.001). The other methods do not show reliability and agreement in comparison to PSC 2 (p < 0.05). 3 of 21 patients (14.3%) developed severe nephrotoxicity post cisplatin chemotherapy. This percentage is much less than the reported 20 - 25% of cases from other studies, probably due to small sample size and biased study population due to strict exclusion criteria. Radionuclide method for evaluating GFR is the most sensitive method for the detection of cisplatin induced nephrotoxicity by showing 3 of 21 patients developing severe nephrotoxicity. PSC 1 was found to be a reliable substitute of PSC 2. The other methods are not reliable for detection of early nephrotoxicity. We will recommend the use of single plasma sampling method (PSC 1) for GFR estimation in monitoring post cisplatin chemotherapy patients.

  20. Chemotherapy for stage 4 melanoma: a three-year experience with cisplatin, DTIC, BCNU, and tamoxifen.

    PubMed

    Reintgen, D; Saba, H

    1993-01-01

    The management of metastatic melanoma has been frustrating from a clinician's point of view because of the relative unresponsiveness of the tumor to chemotherapy and the infrequency of clinically useful objective responses. Although no single agent can be recommended at this time, old standard drugs used in new combinations, immunomodulators, and systematic approaches to dose intensification have created more interest in the chemotherapy of melanoma. Forty-seven consecutive patients with Stage 4 melanoma with measurable disease were treated with combination chemotherapy, consisting of DTIC, BCNU, cisplatin, and tamoxifen. The cycle was repeated every 4 weeks and a total of 6 cycles were delivered. Patients were then restaged to assess the response. Nine patients who were registered during the same time period with Stage 4 disease and elected not to be treated served as the control population. Seventeen patients (46%) achieved a clinical response with six patients (12.7%) undergoing a complete response. The overall survival of all Stage 4 patients in the series was 18% at 3 years. There were significant differences noted in those patients who were treated and the no treatment controls (p = 0.004) and for those patients that received an objective response vs those that progressed on the protocol (p < 0.0001). It is recommended that all patients with Stage 4 melanoma be treated on protocol and results of other trials of systemic therapy for metastatic melanoma be compared to this cisplatin-based regimen instead of a no-treatment arm.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Albumin-to-Alkaline Phosphatase Ratio: A Novel Prognostic Index of Overall Survival in Cisplatin-based Chemotherapy-treated Patients with Metastatic Nasopharyngeal Carcinoma

    PubMed Central

    Nie, Man; Sun, Peng; Chen, Cui; Bi, Xiwen; Wang, Yu; Yang, Hang; Liu, Panpan; Li, Zhiming; Xia, Yi; Jiang, Wenqi

    2017-01-01

    The Albumin-to-Alkaline Phosphatase Ratio (AAPR) has been recently revealed as a prognostic index for hepatocellular carcinoma, whereas its role in metastatic nasopharyngeal cancer (NPC) remains unclear. The aim of this study was to evaluate the clinical value of AAPR in patients with metastatic NPC. We retrospectively reviewed 209 metastatic NPC patients treated with cisplatin-based regimens. Survival data were calculated using the Kaplan-Meier method and were compared using the log-rank test. Univariate and multivariate survival analyses were conducted using the Cox proportional hazards regression methodology. The optimal cutoff level of AAPR for assessing overall survival (OS) was 0.447, which was determined by R software. An AAPR less than 0.447 was significantly associated with a higher lactate dehydrogenase (LDH) level (273 vs. 185 U/L, P = 0.004), a higher EBV DNA viral load (5.59×105 vs. 3.49×104 copies/ml, P = 0.001), and more liver and bone metastases (P = 0.005 and P = 0.001, respectively). Additionally, patients with an AAPR < 0.447 had a shorter overall survival and progression-free survival (hazard ratio: 3.269, 95% confidence interval: 1.710-6.248; HR: 2.295, 95% confidence interval: 1.217-4.331, respectively) than those with an AAPR ≥ 0.447. Our study suggested that the AAPR might be a novel prognostic factor in metastatic NPC patients treated with cisplatin-based regimens. However, a prospective study to validate its prognostic value is needed, and the mechanisms underlying the low AAPR and poor survival in metastatic NPC need to be further investigated. PMID:28382143

  2. Two cases of cisplatin-induced permanent renal failure following neoadjuvant chemotherapy for esophageal cancer

    PubMed Central

    Sasaki, Tomohiko; Motoyama, Satoru; Komatsuda, Atsushi; Shibata, Hiroyuki; Sato, Yusuke; Yoshino, Kei; Wakita, Akiyuki; Saito, Hajime; Anbai, Akira; Jin, Mario; Minamiya, Yoshihiro

    2016-01-01

    Introduction We experienced two esophageal cancer patients who developed severe acute renal failure after neoadjuvant chemotherapy with cisplatin and 5-fluorourasil. Presentation of case After administration of cisplatin, their serum creatinine increased gradually until they required hemodialysis and their renal failure was permanent. In both cases, renal biopsy examination indicated partial recovery of the proximal tubule, but renal function did not recover. After these events, one patient underwent definitive radiotherapy and the other underwent esophagectomy for their esophageal cancers, while continuing dialysis. Both patients are alive without cancer recurrence. Discussion In these two cases of cisplatin-induced renal failure, renal biopsy examination showed only slight disorder of proximal tubules and tendency to recover. Conclusion Although cisplatin-related nephrotoxicity is a well-recognized complication, there have been few reports of renal failure requiring hemodialysis in cancer patients. In this report, we present their clinical courses and the pathological findings of cisplatin-related renal failure. PMID:26851395

  3. On the Discovery, Biological Effects, and Use of Cisplatin and Metallocenes in Anticancer Chemotherapy

    PubMed Central

    Gómez-Ruiz, Santiago; Maksimović-Ivanić, Danijela; Mijatović, Sanja; Kaluđerović, Goran N.

    2012-01-01

    The purpose of this paper is to summarize mode of action of cisplatin on the tumor cells, a brief outlook on the metallocene compounds as antitumor drugs as well as the future tendencies for the use of the latter in anticancer chemotherapy. Molecular mechanisms of cisplatin interaction with DNA, DNA repair mechanisms, and cellular proteins are discussed. Molecular background of the sensitivity and resistance to cisplatin, as well as its influence on the efficacy of the antitumor immune response was evaluated. Furthermore, herein are summarized some metallocenes (titanocene, vanadocene, molybdocene, ferrocene, and zirconocene) with high antitumor activity. PMID:22844263

  4. Non-pineal supratentorial primitive neuro-ectodermal tumors (sPNET) in teenagers and young adults: Time to reconsider cisplatin based chemotherapy after cranio-spinal irradiation?

    PubMed

    Biswas, Swethajit; Burke, Amos; Cherian, Sheen; Williams, Denise; Nicholson, James; Horan, Gail; Jefferies, Sarah; Williams, Michael; Earl, Helena M; Burnet, Neil G; Hatcher, Helen

    2009-07-01

    Supratentorial PNET (sPNET) are rare CNS tumors of embryonal origin arising in children and adults. The treatment of sPNET for all age groups at our cancer center has been based on the management of medulloblastoma (MB), involving neurosurgical debulking followed by cranio-spinal irradiation (CSI) and systemic chemotherapy. Medical records were reviewed to gather demographic and clinical data about all embryonal CNS tumors in children and adults from 2001 to 2007. Tumor pathology, clinical management and survival data were also assessed, particularly as regards those patients who received the Packer chemotherapy regimen for either sPNET or MB. Eleven patients (five children and six adults) were identified with non-pineal sPNET, three children with pineal sPNET, and 19 patients (18 children and 1 adult) with MB. There was no difference in overall survival (OS) rates between pediatric and adult sPNET. When all sPNET were compared to all MB, 5-year OS was 14% versus 73%, respectively, but was only 9% for non-pineal sPNET. When only considering those patients treated with the Packer chemotherapy regimen, the 5-year OS was 12% for sPNET versus 79% for MB. This retrospective study demonstrates that non-pineal sPNET are clinically distinct from MB and are resistant to the Packer chemotherapy regimen. We suggest that it is time to reconsider the use of this regimen in teenage and young adult non-pineal sPNET and to investigate the utility of alternative approaches. (c) 2009 Wiley-Liss, Inc.

  5. Renal function of cancer patients "fit" for Cisplatin chemotherapy: physician perspective.

    PubMed

    Montoya, J; Luna, H G; Amparo, J R; Casasola, C; Cristal-Luna, G

    2014-07-01

    Renal insufficiency is prevalent among cancer patients and it poses a hindrance in using cisplatin. We sought to describe the baseline renal function of our patients who were considered "fit" for cisplatin, along with saline hydration and mannitol diuresis, and determine occurrence of nephrotoxicity during chemotherapy. A retrospective study from 2008 to 2012 of 100 patients who were given cisplatin was done. Demographic and clinical variables were recorded. Creatinine Clearance was calculated using Cockcroft-Gault formula. Nephrotoxicity was defined as an increase of 0.5mg/dL or more after cisplatin infusion. Descriptive statistics, ANOVA, logistic regression analysis were done. A total of 100 patients were "fit" for cisplatin, with a mean age of 52 years, mean creatinine of 0.83mg/dL, CrCl of 94.14ml/ min, and ECOG performance status of 0-2. 12 patients have Chronic Kidney Disease (CKD) stage of 3, 42 patients with stage 2, 46 patients with stage 1. After cisplatin treatment, mean creatinine increased to 0.95mg/dL, and mean CrCl decreased to 83.7ml/min. Nine patients developed nephrotoxicity; all resolved with hydration. Patients with nephrotoxicity were significantly different from those without, in terms of weight p 0.012. None of the variables were predictors of nephrotoxicity. With hydration and mannitol diuresis, patients with ECOG 2, normal creatinine, CKD stage 3 or better, CrCl of 50ml/min and above are "fit" for cisplatin. During the study period, 9% of the patients "fit" for cisplatin developed nephrotoxicity, all resolved with conservative management. There was an increase in mean creatinine and a decrease in the mean CrCl after cisplatin.

  6. The impact of a solitary kidney on tolerability to gemcitabine plus cisplatin chemotherapy in urothelial carcinoma patients: a retrospective study.

    PubMed

    Kondo, Masahiro; Hotta, Yuji; Ando, Ryosuke; Yasui, Takahiro; Kimura, Kazunori

    2017-05-01

    There is little information on tolerability to cisplatin-based chemotherapies in patients with a solitary kidney after nephroureterectomy. We evaluated the impact of having a solitary kidney on tolerability to gemcitabine plus cisplatin (GC) chemotherapy in urothelial carcinoma patients. We retrospectively reviewed medical records of patients treated between August 2007 and November 2015. Eligible patients had received GC as first-line chemotherapy, including as neoadjuvant and adjuvant treatment. Patients who commenced GC chemotherapy after nephroureterectomy comprised the solitary kidney (SK) group; the remaining patients (i.e., those with both kidneys) comprised the BK group. Incidences of hematologic toxicities and renal insufficiency were examined and compared between two groups. There were 16 patients in the SK group and 31 in the BK group. The incidence of hematologic toxicity (grade 3/4) was not significantly different between the two groups (neutropenia: 68.8 vs. 74.2%, respectively (P = 0.959); thrombocytopenia: 31.2 vs. 51.6%, respectively (P = 0.307); and anemia: 12.5 vs. 38.7%, respectively (P = 0.094)). Multivariate analysis revealed no statistically significant association between having a SK and severe hematologic toxicities. Moreover, no significant differences were observed in the incidence of acute kidney injury. The mean differences in serum creatinine and estimated glomerular filtration rate between baseline and each post-chemotherapy cycle were similar when comparing the SK and BK groups. There is no evidence that tolerability to GC chemotherapy is inferior in patients with a solitary kidney. Therefore, there may be no need to avoid administering CDDP-based chemotherapy to such patients.

  7. Is Gemcitabine and Cisplatin Induction Chemotherapy Superior in Locoregionally Advanced Nasopharyngeal Carcinoma?

    PubMed Central

    Zheng, Wei; Qiu, Sufang; Huang, Lingling; Pan, Jianji

    2015-01-01

    Objective: To investigate the outcome of locoregionally advanced nasopharyngeal carcinoma (NPC) treated with induction chemotherapy followed by chemoradiotherapy. Methods: Between June 2005 and October 2007, 604 patients with locoregionally advanced NPC were analyzed, of whom 399 and 205 were treated with conventional radiotherapy and intensity-modulated radiotherapy (IMRT) respectively. Meanwhile, 153 patients received concurrent chemotherapy, and 520 were given induction chemotherapy. Results: With a median follow-up time of 65 months, the 3-, and 5-year overall survival (OS), locoregional free survival (LRFS), and distant-metastasis free survival (DMFS) rates were 82.5% vs. 72.6%, 90.6% vs. 87.1%, and 82.5% vs. 81.2%, respectively. Induction chemotherapy was not an independent prognostic factor for OS (P=0.193) or LRFS, but there was a positive tendency for DMFS (P=0.088). GP regimen (gemcitabine + cisplatin) was an independent prognostic factor for OS (P = 0.038) and it had a trend toward improved DMFS (P = 0.109). TP regimen (taxol + cisplatin) was only a significant prognostic factor for DMFS (P =0.038). Conclusions: Adding induction chemotherapy had no survival benefit, but GP regimen benefited overall survival and had a trend toward improved DMFS. GP regimen may be superior to TP/FP regimen (fluorouracil + cisplatin) in treating locoregionally advanced NPC. PMID:26430402

  8. [A case of small cell carcinoma in the urinary bladder responding to gemcitabine/cisplatin combination therapy as neoadjuvant chemotherapy].

    PubMed

    Shirato, Akitomi; Shimamoto, Kenji; Ozawa, Akira; Tanji, Nozomu; Yokoyama, Masayoshi

    2006-12-01

    We report a case of primary small cell carcinoma of the urinary bladder. A 79-year-old man with the chief complaints of macrohematuria and pollakisuria was admitted to our hospital. Cystoscopy and computed tomography (CT) revealed a non-papillary broad-based bladder tumor. Histological diagnosis was small cell carcinoma of the urinary bladder, and he underwent 3 courses of neoadjuvant chemotherapy including gemcitabine and cisplatin with a preoperative diagnosis of cT3bN0M0. After the chemotherapy, cystoscopy and CT showed complete remission. Total cystectomy with ileal conduit was performed following 3 courses of chemotherapy. Microscopic examination revealed that the small cell carcinoma had disappeared and the converted squamous cell carcinoma remained only in a small part of the specimens. The patient was carefully followed for 10 months after operation, with no tumor recurrence.

  9. Induction Chemotherapy with Cisplatin and 5-Fluorouracil in Advanced Head and Neck Cancers: A Short Term Response Evaluation

    PubMed Central

    Rao, Raghavendra; Shenoy, Vijendra; Hegde, Mahesh Chandra; Prasad, Vishnu; Prasad, Krishna

    2015-01-01

    Background Considering the uprising number of Head and neck cancer in the state with limited options of medical and surgical treatment, the focus of this study involved on chemotherapy in advanced Head and neck cancers. The aim of this study was to evaluate the efficacy and toxicity of combination of Cisplatin and 5-Fluorouracil (PF) as induction chemotherapy in patients in locally advanced squamous cell cancer of head and neck. Materials and Methods Forty four patients with previously untreated stage III -IV advanced and inoperable cases were included in this prospective study. Induction chemotherapy consisted of 3 cycles of Cisplatin 100mg/mt2 as infusion on day 1, 5-Fluorouracil of 750mg/mt2 on day 2, 5-Fluorouracil of 1000mg/mt2 as infusion on day 3 in an inpatient basis. Cycles were repeated with an interval of 21 days. Patients were evaluated within a period of 3 weeks at the end of completion of third cycle of chemotherapy. Post chemotherapy local therapy was individualized based on the response, site and stage of the tumour. Results Out of 44 eligible and evaluable patients, major dominance was noted in male group constituting 68%. After induction chemotherapy 58.8% of stage III experienced stable response, & 44% had partial response. In stage IV, 44% showed a stable response and 33.3% had partial response. But in comparison to primary tumour response and nodal response, which had a significant clinical response, the overall response of malignancy with respect to stage and site specificity was clinically insignificant. Moderate adverse reaction was noted in 47.6% and 42.1% had mild reactions. Majority of patients experienced grade 3 adverse events, of which anaemia in females and leucopenia in males pre-dominated. Conclusion With the use of cisplatin and 5-FU as induction chemotherapy agents in advanced and inoperable squamous cell carcinoma of head and neck, a distinct benefit was seen in stabilizing the tumour from progression. But achieving a significant

  10. Pediatric and Young Adult Nasopharyngeal Carcinoma Patients Treated With Preradiation Cisplatin and Docetaxel Chemotherapy

    SciTech Connect

    Varan, Ali Ozyar, Enis; Corapcioglu, Funda; Koeksal, Yavuz; Aydin, Burca; Yazici, Nalan; Akyuez, Canan; Bueyuekpamukcu, Muenevver

    2009-03-15

    Purpose: To evaluate treatment results for pediatric and young adult (aged <21 years) patients with nonmetastatic nasopharyngeal carcinoma treated with neoadjuvant cisplatin + docetaxel and radiotherapy. Methods and Materials: Ten patients with nasopharyngeal carcinoma who received diagnoses between 2004 and 2007 were treated with four cycles of cisplatin 100 mg/m{sup 2} + docetaxel 75 mg/m{sup 2} on Day 1 with premedication every 3 weeks. All patients were treated with fractionated external beam radiotherapy after chemotherapy to a median dose of 59.4 Gy (range, 54-59.4 Gy) to the primary disease and 40 Gy to the supraclavicular field with the clavicles shielded. Five children were monitored with serum EBV DNA quantification at diagnosis, after each cycle of chemotherapy, before radiotherapy, and at follow-up. Results: The median age of the patients was 14 years (range, 9-20 years), with a male:female ratio of 6:4. Stage distribution was as follows: 2 patients had Stage IIb disease, 2 had Stage III, 4 had Stage IVa, and 2 had Stage IVb disease. After cisplatin+docetaxel chemotherapy 1 patient had a complete response, 5 had a partial response, 3 had stable disease, and 1 had disease progression. The 2-year overall survival rate in our series was 90% and the event-free survival rate was 70%. No major chemotherapy toxicity was observed. The EBV DNA titers were higher in 2 of the 5 monitored patients at the time of diagnosis. Conclusion: As neoadjuvant chemotherapy before radiotherapy, the cisplatin+docetaxel combination is safe for use in the treatment of childhood nasopharyngeal carcinoma.

  11. Seizure following chemotherapy (paclitaxel and cisplatin) in a patient of carcinoma cervix

    PubMed Central

    Dana, Rohitashwa; Spartacus, R. K.; Mutha, Shweta; Bhat, Prashanth

    2016-01-01

    Cisplatin and paclitaxel both can cause peripheral neurotoxicity as an adverse effect; however, central nervous system neurotoxicity in the form of seizures is rare. We report a case of a 36-year-old female patient of metastatic carcinoma cervix, who developed seizure shortly after cisplatin infusion. Her laboratory investigations were within normal limits. Computed tomography scan and magnetic resonance imaging of the brain did not reveal brain primary metastasis or meningeal carcinomatosis. She had no complaints of fever, no signs and symptoms of infection, and no history of seizure nor was she on any medication predisposing to such an event. Excluding several causes, seizure was thought to be most likely related to the chemotherapy and cisplatin was the more likely agent in view of observed temporal relationship with the adverse event. PMID:28066118

  12. Seizure following chemotherapy (paclitaxel and cisplatin) in a patient of carcinoma cervix.

    PubMed

    Dana, Rohitashwa; Spartacus, R K; Mutha, Shweta; Bhat, Prashanth

    2016-01-01

    Cisplatin and paclitaxel both can cause peripheral neurotoxicity as an adverse effect; however, central nervous system neurotoxicity in the form of seizures is rare. We report a case of a 36-year-old female patient of metastatic carcinoma cervix, who developed seizure shortly after cisplatin infusion. Her laboratory investigations were within normal limits. Computed tomography scan and magnetic resonance imaging of the brain did not reveal brain primary metastasis or meningeal carcinomatosis. She had no complaints of fever, no signs and symptoms of infection, and no history of seizure nor was she on any medication predisposing to such an event. Excluding several causes, seizure was thought to be most likely related to the chemotherapy and cisplatin was the more likely agent in view of observed temporal relationship with the adverse event.

  13. First-line chemotherapy with liposomal doxorubicin plus cisplatin for patients with advanced malignant pleural mesothelioma: phase II trial

    PubMed Central

    Arrieta, Ó; Medina, L A; Estrada-Lobato, E; Hernández-Pedro, N; Villanueva-Rodríguez, G; Martínez-Barrera, L; Macedo, E O; López-Rodríguez, V; Motola-Kuba, D; Corona-Cruz, J F

    2012-01-01

    Background: Chemotherapy based on platinum is the standard treatment for unresectable malignant pleural mesothelioma (MPM). Liposomal doxorubicin (LD) consists of pegylated phospholipid vesicles that encapsulate doxorubicin-enhancing liposome deposition in the tumour. We evaluated the toxicity profile and anti-tumour activity of cisplatin plus LD in untreated patients with MPM, as well as 99mTc-LD distribution in MPM lesions after chemotherapy administration. Methods: A total of 38 patients with non-resectable MPM received LD 40 mg m−2 and cisplatin 60 mg m−2 every 21 days. Gamma camera images of 99mTc-LD were acquired to evaluate LD accumulation in measurable tumour tissue. The study was registered in Clinical Trials (NCT00886028). Results: In all, 72% of patients were stage III and 28% were stage IV. Eighty four percent and 16% have high and low risk acording EORTC respectively. The median time to progression was 4.6 months (95% confidence interval (95% CI: 3.4–5.9 months), and median overall survival (OS) was 19.6 months (15.2–37.2 months). Patients that responded to chemotherapy treatment had better survival than patients who did not. Functional physical scales, dysnea, cough, and chest/arm pain demonstrated improvement. The accumulation ratio of LD in tumour and soft tissues vs liver was 0.78±0.16 and 0.29±0.09, respectively. After 1 h of administration, LD uptake in tumour tissue was higher than in soft tissue (P< 0.001). Conclusion: The combination of LD and cisplatin results in an active therapeutic regimen for unresectable MPM, with an acceptable toxicity profile and improvement in quality of life. 99mTc-LD showed higher levels of tumour uptake as compared with surrounding tissues. PMID:22353806

  14. Reduced and Compressed Cisplatin-Based Chemotherapy in Children and Adolescents With Intermediate-Risk Extracranial Malignant Germ Cell Tumors: A Report From the Children's Oncology Group.

    PubMed

    Shaikh, Furqan; Cullen, John W; Olson, Thomas A; Pashankar, Farzana; Malogolowkin, Marcio H; Amatruda, James F; Villaluna, Doojduen; Krailo, Mark; Billmire, Deborah F; Rescorla, Frederick J; Egler, Rachel A; Dicken, Bryan J; Ross, Jonathan H; Schlatter, Marc; Rodriguez-Galindo, Carlos; Frazier, A Lindsay

    2017-04-10

    Purpose To investigate whether event-free survival (EFS) can be maintained among children and adolescents with intermediate-risk (IR) malignant germ cell tumors (MGCT) if the administration of cisplatin, etoposide, and bleomycin (PEb) is reduced from four to three cycles and compressed from 5 to 3 days per cycle. Patients and Methods In a phase 3, single-arm trial, patients with IR MGCT (stage II-IV testicular, II-III ovarian, I-II extragonadal, or stage I gonadal tumors with subsequent recurrence) received three cycles of PEb. A parametric comparator model specified that the observed EFS rate should not be significantly < 92%. As recommended for trials that test a reduction of therapy, a one-sided P value ≤ .10 was used to indicate statistical significance. In a post hoc analysis, we also compared results to the EFS rate of comparable patients treated with four cycles of PEb in two prior studies. Results Among 210 eligible patients enrolled from 2003 to 2011, 4-year EFS (EFS4) rate was 89% (95% confidence interval, 83% to 92%), which was significantly lower than the 92% threshold of the comparison model ( P = .08). Among 181 newly diagnosed patients, the EFS4 rate was 87%, compared with 92% for 92 comparable children in the historical cohort ( P = .15). The EFS4 rate was significantly associated with stage (stage I, 100%; stage II, 92%; stage III, 85%; and stage IV, 54%; P < .001). Conclusion The EFS rate for children with IR MGCT observed after three cycles of PEb was less than that of a prespecified parametric model, particularly for patients with higher-stage tumors. These data do not support a reduction in the number of cycles of PEb from four to three. However, further investigation of a reduction in the number of cycles for patients with lower-stage tumors is warranted.

  15. Postoperative chemotherapy in gastric cancer, consisting of etoposide, doxorubicin and cisplatin, followed by radiotherapy with concomitant cisplatin: A feasibility study

    PubMed Central

    SHULMAN, KATERINA; HAIM, NISSIM; WOLLNER, MIRA; BERNSTEIN, ZVI; ABDAH-BORTNYAK, ROXYLANA; BAR-SELA, GIL

    2012-01-01

    The prognosis following surgical treatment of gastric carcinoma (GC) or gastroesophageal junction (GEJ) adenocarcinoma remains poor. Although adjuvant chemo-radiotherapy with 5-fluorouracil has been shown to be beneficial, a high rate of distant failure has been reported. Thus, the toxicity profile and efficacy of an intensified chemo-radiotherapy regimen following complete or near-complete resection of GC was evaluated. Patients who underwent surgery for GC were eligible for evaluation. Treatment consisted of four cycles of modified EAP: etoposide 100 mg/m2, days 1–3; cisplatin 27 mg/m2, days 1–3; and adriamycin 40 mg/m2, day 1; every 21 days, followed by a course of radiotherapy (45 Gy; 1.8 Gy/fr) combined with weekly cisplatin 40 mg/m2. In total, 40 patients were included in the analysis. Median follow-up was 34 months from the onset of chemotherapy. Microscopic stage IV disease and/or R1 resection were found in 11 patients. For these patients, the median progression-free survival was 6.5 months, and overall survival 9.5 months, compared to 25 and 54 months, respectively, for the remaining 29 patients. In the latter subgroup, longer disease-free survival was associated with average dose intensity of >90% for the four cycles of EAP. The predominant grade 3–4 toxicities during EAP-chemotherapy were hematological adverse events. Nevertheless, the rate of severe non-hematologic toxicity reached 60%. There was one toxicity-related mortality. During the chemo-radiotherapy course, 39% of patients experienced grade 3–4 non-hematologic toxicities. It was concluded that the high toxicity rate of this regimen does not justify further evaluation of this postoperative protocol. Chemo-radiotherapy for R1 or pathological microscopic M1 patients does not appear to be justified. PMID:22783410

  16. Preconditioning chemotherapy with cisplatin enhances the antitumor activity of cytokine-induced killer cells in a murine melanoma model.

    PubMed

    Chen, Jing; Huang, Xiang; Huang, Guichun; Chen, Yitian; Chen, Longbang; Song, Haizhu

    2012-04-01

    Accumulating evidence has indicated that preconditioning chemotherapy could eliminate the suppressive factors in antitumor immune response, thereby leading to the full release of the efficacy of the subsequent immunotherapy. In this study, a single subtoxic dose (5 mg/kg, intraperitoneally) of cisplatin was chosen as the preconditioning chemotherapy in combination with cytokine-induced killer (CIK) cells (4×10(6), intravenously) to treat the murine B16 melanoma xenografts. It was found that cisplatin pretreatment could enhance the antitumor activity of CIK cells. To explore the potential mechanisms underlying the efficacy-enhancing effect of cisplatin, the in vivo trafficking and distribution of the infused CIK cells were traced. It was found that cisplatin could augment the homing ability of CIK cells into the tumor, tumor-draining lymph nodes (TDLNs), and spleen tissues. The endogenous effector cells, CD3(+) T lymphocytes also had an increased accumulation in the tumor and TDLNs after cisplatin precondition. Moreover, cisplatin could also modulate the percentages of myeloid cells, thus encouraging immune responses by increasing the percentages of dendritic cells and relieving the immunosuppression by preferentially eliminating the myeloid-derived suppressor cells. In conclusion, our findings suggested that cisplatin preconditioning chemotherapy could enhance the antitumor activity of CIK cells in a murine melanoma model, and this efficacy-enhancing effect was attributed to the augmented homing ability of exogenous and endogenous effector cells and the modulation of the myeloid cells.

  17. Clinical Significance of Early Changes in Circulating Tumor Cells from Patients Receiving First-Line Cisplatin-Based Chemotherapy for Metastatic Urothelial Carcinoma1

    PubMed Central

    Fina, Emanuela; Necchi, Andrea; Giannatempo, Patrizia; Colecchia, Maurizio; Raggi, Daniele; Daidone, Maria Grazia; Cappelletti, Vera

    2016-01-01

    Background: The therapeutic paradigm of metastatic urothelial carcinoma (UC) is rapidly shifting and new biomarkers are needed to enhance patient selection. Objective: Early identification of dynamic predictors of outcome may be a key to optimize the sequence of effective therapies in metastatic UC patients. Methods: Blood samples from patients receiving first-line MVAC chemotherapy were collected at baseline (T0) and after 2 cycles (T2). Samples were processed by immunomagnetic beads (AdnaTest ProstateCancerSelect kit) and the expression of EPCAM, MUC1 and ERBB2 was studied using multiplex-PCR. Circulating tumor cell (CTC) positivity and cutoffs, obtained by receiver operator characteristic (ROC) curve analysis in healthy donors, were: ≥1 positive marker among EPCAM (≥0.40 ng/μl), MUC1 (≥0.10 ng/μl) and ERBB2 (≥0.20 ng/μl). CTC variation (T0/T2) was split in favorable (+/–, –/–, –/+) and unfavorable groups (+/+). Cox regression analyses evaluated associations with clinical factors. Results: In this pilot study to assess a new CTC detection method, among 31 evaluable patients, 17 (54.8%) were CTC-positive at T0. No association was found between CTC and objective response to MVAC. CTC dynamic changes better predicted 3-year progression-free (PFS) and overall survival (OS) compared to CTC status assessed at single time points. Unfavorable trend was univariably detrimental on 3-year PFS (10% vs. 49.2%, p = 0.006) and OS (20% vs. 63.5%, p = 0.017). Significance was maintained after controlling for liver metastases (p = 0.031 and p = 0.025 for PFS and OS) and MSKCC score (p = 0.014 and 0.025). Conclusions: Newly described early CTC changes during chemotherapy might be useful to improve our prognostic ability. Pending validation, these results could fulfill the promise to help accelerating therapeutic sequences. PMID:28035320

  18. Synergism between propolis and hyperthermal intraperitoneal chemotherapy with cisplatin on ehrlich ascites tumor in mice.

    PubMed

    Oršolić, Nada; Car, Nikola; Lisičić, Duje; Benković, Vesna; Knežević, Anica Horvat; Dikić, Domagoj; Petrik, József

    2013-12-01

    We investigated antitumor, genotoxic, chemopreventive, and immunostimulative effects of local chemoimmunotherapy and hyperthermal intraperitoneal chemotherapy (HIPEC) in a mouse-bearing Ehrlich ascites tumor (EAT). Mice were treated with water-soluble derivative of propolis (WSDP) at a dose of 50 mg kg(-1) , 7 and 3 days before implantation of EAT cells, whereas cisplatin (5 or 10 mg kg(-1) ) was injected 3 days after implantation of EAT cells at 37°C and 43°C. The following variables were analyzed: the total number of cells, differential count of the cells present in the peritoneal cavity, functional activity of macrophages, comet assay, and micronucleus assay. The combination of WSDP + CIS 5 mg kg(-1) at 37°C resulted in tumor growth inhibition and increased the survival of mice by additional 115.25%. WSDP with HIPEC increased the survival of mice by additional 160.3% as compared with HIPEC. WSDP reduced cisplatin toxic and genotoxic effect to normal cells without affecting cisplatin cytotoxicity on EAT cells. In addition, WSDP with HIPEC increased the cytotoxic actions of macrophages to tumor cells. Water-soluble derivative of propolis increases macrophage activity and sensitivity of tumor cells to HIPEC and reduces cisplatin toxicity to normal cells. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

  19. MCL-1 is the key target of adjuvant chemotherapy to reverse the cisplatin-resistance in NSCLC.

    PubMed

    Ma, Jun; Zhao, Zhenxian; Wu, Kaiming; Xu, Zhe; Liu, Kuanzhi

    2016-08-10

    Cisplatin is one of the most effective chemotherapeutic agents for the treatment of lung cancer. However, the acquired resistance occurred in cancer cells limits the clinical application of cisplatin. MCL-1, which is an important member in the pro-survival Bcl-2 family, plays a critical role in multidrug resistance (MDR). The aim of the present study is to investigate the value of Pan-Bcl-2 inhibitor as sensitizer for the chemotherapy of cisplatin-resistant non-small cell lung cancer (NSCLC) cells. We found the obatoclax but not the ABT-737 significantly decreased the IC50 (half maximal inhibitory concentration) of cisplatin in cisplatin-resistant NSCLC cells. Furthermore, we demonstrated that the mechanism of obatoclax-promoted cell death induced by cisplatin was dependent on the inhibition of MCL-1, which couldn't be inhibited by ABT-737 but is the target of obatoclax. Moreover, inhibition of MCL-1 recovered the function of NOXA and BAK in cisplatin-resistant NSCLC cells, leading to the promotion of mitochondrial apoptosis induced by cisplatin. Interestingly, our date indicated the obatoclax also reversed the cross-resistance in cisplatin-resistant NSCLC cells. Therefore, we demonstrated that the targeted therapy with MCL-1 inhibitors, such as obatoclax, may represent a novel strategy for cancer therapy.

  20. Transarterial Infusion Chemotherapy Using Cisplatin-Lipiodol Suspension With or Without Embolization for Unresectable Hepatocellular Carcinoma

    SciTech Connect

    Kawaoka, Tomokazu; Aikata, Hiroshi Takaki, Shintaro; Katamura, Yoshio; Hiramatsu, Akira; Waki, Koji; Takahashi, Shoichi; Hieda, Masashi; Toyota, Naoyuki; Ito, Katsuhide; Chayama, Kazuaki

    2009-07-15

    We evaluate the long-term prognosis and prognostic factors in patients treated with transarterial infusion chemotherapy using cisplatin-lipiodol (CDDP/LPD) suspension with or without embolization for unresectable hepatocellular carcinoma (HCC). Study subjects were 107 patients with HCC treated with repeated transarterial infusion chemotherapy alone using CDDP/LPD (adjusted as CDDP 10mg/LPD 1ml). The median number of transarterial infusion procedures was two (range, one to nine), the mean dose of CDDP per transarterial infusion chemotherapy session was 30 mg (range, 5.0-67.5 mg), and the median total dose of transarterial infusion chemotherapy per patient was 60 mg (range, 10-390 mg). Survival rates were 86% at 1 year, 40% at 3 years, 20% at 5 years, and 16% at 7 years. For patients with >90% LPD accumulation after the first transarterial infusion chemotherapy, rates were 98% at 1 year, 60% at 3 years, and 22% at 5 years. Multivariate analysis identified >90% LPD accumulation after the first transarterial infusion chemotherapy (p = 0.001), absence of portal vein tumor thrombosis (PVTT; p < 0.001), and Child-Pugh class A (p = 0.012) as independent determinants of survival. Anaphylactic shock was observed in two patients, at the fifth transarterial infusion chemotherapy session in one and the ninth in the other. In conclusion, transarterial infusion chemotherapy with CDDP/LPD appears to be a useful treatment option for patients with unresectable HCC without PVTT and in Child-Pugh class A. LPD accumulation after the first transarterial infusion chemotherapy is an important prognostic factor. Careful consideration should be given to the possibility of anaphylactic shock upon repeat infusion with CDDP/LPD.

  1. A Phase II Tolerability Study of Cisplatin Plus Docetaxel as Adjuvant Chemotherapy for Resected Non-small Cell Lung Cancer

    PubMed Central

    Azzoli, Christopher G.; Krug, Lee M.; Miller, Vincent A.; Rizvi, Naiyer A.; Kris, Mark G.; Dunne, Megan; Farmer, Amy; Pizzo, Barbara; Tyson, Leslie; Seeger, Teresa; Coleman, Barbara; Moore, Erin; Lastinger, Lauren; Venkatraman, Ennapadam; Rudin, Charles M.

    2013-01-01

    Introduction We undertook this phase II study to measure postoperative drug delivery and toxicity of cisplatin plus docetaxel in patients with resected stage I-III non-small cell lung cancer. Methods The primary endpoint was amount of cisplatin delivered over a planned four cycles of adjuvant chemotherapy. Statistical design required a cohort to close if the regimen proved unlikely to improve cisplatin delivery compared with published phase III data. The first cohort was treated with docetaxel 35 mg/m2 intravenously (IV) on days 1, 8, and 15, and cisplatin 80 mg/m2 IV on day 15, every 4 weeks for four planned cycles. A second cohort was treated with docetaxel 75 mg/m2 IV plus cisplatin 80 mg/m2 IV on day 1 every 3 weeks for four planned cycles. Results Sixteen patients were treated with weekly docetaxel and cisplatin every 4 weeks, with five of 16 (31%) unable to complete three cycles. Subsequently, 11 patients were treated with docetaxel and cisplatin every 3 weeks, with six of 11 (55%) unable to complete three cycles. Among the 11 patients who failed to complete three cycles, the reasons for stopping included one or more of the following: fatigue (n = 8), nausea (n = 4), febrile neutropenia (n = 1), hypotension (n = 1), and nephrotoxicity (n = 1). Conclusions The combination of cisplatin at 80 mg/m2 with docetaxel 35 mg/m2 weekly or 75 mg/m2 every 3 weeks is no better tolerated than older chemotherapy regimens. The most common reason to stop chemotherapy was intolerable fatigue. These results suggest that the most common dose-limiting toxicities are attributable to the cisplatin, given similar problems were encountered whether the docetaxel was delivered as a single dose every 3 weeks or as a lower weekly dose. PMID:17607120

  2. Early results of a randomized two-by-two factorial phase II trial comparing neoadjuvant chemotherapy with two and four courses of cisplatin/S-1 and docetaxel/cisplatin/S-1 as neoadjuvant chemotherapy for locally advanced gastric cancer.

    PubMed

    Aoyama, T; Nishikawa, K; Fujitani, K; Tanabe, K; Ito, S; Matsui, T; Miki, A; Nemoto, H; Sakamaki, K; Fukunaga, T; Kimura, Y; Hirabayashi, N; Yoshikawa, T

    2017-08-01

    Neoadjuvant chemotherapy (NAC) is a promising method of improving the survival of resectable gastric cancer. Cisplatin/S-1 (CS) and docetaxel/cisplatin/S-1 (DCS) are both effective against metastatic gastric cancer. This report clarified the impact of these regimens on early endpoints, including the pathological responses, chemotherapy-related toxicities, and surgical results. Patients with M0 and either T4 or T3 in case of junctional cancer or scirrhous type received two or four courses of cisplatin (60 mg/m2 at day 8)/S-1 (80 mg/m2 for 21 days with 1 week rest) or docetaxel (40 mg/m2 at day 1)/cisplatin (60 mg/m2 at day 1)/S-1 (80 mg/m2 for 14 days with 2 weeks rest) as NAC. Patients then underwent D2 gastrectomy and adjuvant S-1 chemotherapy for 1 year. The primary endpoint was the 3-year overall survival. Between October 2011 and September 2014, 132 patients were assigned to receive CS (n = 66; 33 in 2 courses and 33 in 4 courses) or DCS (n = 66; 33 in 2 courses and 33 in 4 courses). The respective major grade 3 or 4 hematological toxicities (CS/DCS) were leukocytopenia (14.1%/26.2%), neutropenia (29.7%/47.7%), anemia (14.1%/12.3%), and platelet reduction (3.1%/1.5%). The rate of pathological response, defined as a complete response or < 10% residual cancer remaining, was 19.4% in the CS group and 15.4% in the DCS group, and 15.6% in the two-course group and 19.0% in the 4-course group. The R0 resection rate was 72.7% in the CS group and 81.8% in the DCS group and 80.3% in the two-course group and the 74.2% in the four-course group. No treatment-related deaths were observed. Our results do not support three-drug therapy with a taxane over two-drug therapy, or any further treatment beyond two cycles as an attractive candidate for the test arm of NAC.

  3. Vasospastic angina likely related to cisplatin-containing chemotherapy and thoracic irradiation for lung cancer.

    PubMed

    Fukuda, M; Oka, M; Itoh, N; Sakamoto, T; Mori, H; Hayakawa, A; Kohno, S

    1999-05-01

    Vasospastic angina is rarely observed during cancer treatment. The present report describes two males with lung cancer, aged 73 and 61, who developed vasospastic angina during combination treatment of cisplatin-containing chemotherapy and thoracic irradiation. As both patients have smoked and their ages are typical for patients with coronary artery disease, such events may be incidental. However, oncologists should be aware of the possible development of myocardial ischemia during or following administration of antineoplastic agents, especially in elderly patients with pre-existing coronary risk factors or a history of thoracic radiotherapy.

  4. Gemcitabine and cisplatin neoadjuvant chemotherapy for muscle-invasive urothelial carcinoma: Predicting response and assessing outcomes

    PubMed Central

    Gandhi, Nilay M.; Baras, Alexander; Munari, Enrico; Faraj, Sheila; Reis, Leonardo O.; Liu, Jen-Jane; Kates, Max; Hoque, Mohammad Obaidul; Berman, David; Hahn, Noah M.; Eisenberger, Mario; Netto, George J.; Schoenberg, Mark P.; Bivalacqua, Trinity J.

    2015-01-01

    Purpose To evaluate gemcitabine-cisplatin (GC) neoadjuvant cisplatin-based chemotherapy (NAC) for pathologic response (pR) and cancer-specific outcomes following radical cystectomy (RC) for muscle-invasive bladder cancer and identify clinical parameters associated with pR. Materials and methods We studied 150 consecutive cases of muscle-invasive bladder cancer that received GC NAC followed by open RC (2000–2013). A cohort of 121 patients treated by RC alone was used for comparison. Pathologic response and cancer-specific survival (CSS) were compared. We created the Johns Hopkins Hospital Dose Index to characterize chemotherapeutic dosing regimens and accurately assess sufficient neoadjuvant dosing regarding patient tolerance. Results No significant difference was noted in 5-year CSS between GC NAC (58%) and non-NAC cohorts (61%). The median follow-up was 19.6 months (GC NAC) and 106.5 months (non-NAC). Patients with residual non–muscle-invasive disease after GC NAC exhibit similar 5-year CSS relative to patients with no residual carcinoma (P = 0.99). NAC pR (≤pT1) demonstrated improved 5-year CSS rates (90.6% vs. 27.1%, P < 0.01) and decreased nodal positivity rates (0% vs. 41.3%, P < 0.01) when compared with nonresponders (≥pT2). Clinicopathologic outcomes were inferior in NAC pathologic nonresponders when compared with the entire RC-only–treated cohort. A lower pathologic nonresponder rate was seen in patients tolerating sufficient dosing of NAC as stratified by the Johns Hopkins Hospital Dose Index (P = 0.049), congruent with the National Comprehensive Cancer Network guidelines. A multivariate classification tree model demonstrated 60 years of age or younger and clinical stage cT2 as significant of NAC response (P < 0.05). Conclusions Pathologic nonresponders fare worse than patients proceeding directly to RC alone do. Multiple predictive models incorporating clinical, histopathologic, and molecular features are currently being developed to identify

  5. Mesoporous Silica Nanoparticles Loaded with Cisplatin and Phthalocyanine for Combination Chemotherapy and Photodynamic Therapy in vitro.

    PubMed

    Vivero-Escoto, Juan L; Elnagheeb, Maram

    2015-12-16

    Mesoporous silica nanoparticles (MSNs) have been synthesized and loaded with both aluminum chloride phthalocyanine (AlClPc) and cisplatin as combinatorial therapeutics for treating cancer. The structural and photophysical properties of the MSN materials were characterized by different spectroscopic and microscopic techniques. Intracellular uptake and cytotoxicity were evaluated in human cervical cancer (HeLa) cells by confocal laser scanning microscopy (CLSM) and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assays, respectively. The CLSM experiments showed that the MSN materials can be readily internalized in HeLa cells. The cytotoxic experiments demonstrated that, after light exposure, the combination of both AlClPc and cisplatin compounds in the same MSN platform potentiate the toxic effect against HeLa cells in comparison to the control AlClPc-MSN and cisplatin-MSN materials. These results show the potential of using MSN platforms as nanocarriers for combination photodynamic and chemotherapies to treat cancer.

  6. Mesoporous Silica Nanoparticles Loaded with Cisplatin and Phthalocyanine for Combination Chemotherapy and Photodynamic Therapy in vitro

    PubMed Central

    Vivero-Escoto, Juan L.; Elnagheeb, Maram

    2015-01-01

    Mesoporous silica nanoparticles (MSNs) have been synthesized and loaded with both aluminum chloride phthalocyanine (AlClPc) and cisplatin as combinatorial therapeutics for treating cancer. The structural and photophysical properties of the MSN materials were characterized by different spectroscopic and microscopic techniques. Intracellular uptake and cytotoxicity were evaluated in human cervical cancer (HeLa) cells by confocal laser scanning microscopy (CLSM) and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assays, respectively. The CLSM experiments showed that the MSN materials can be readily internalized in HeLa cells. The cytotoxic experiments demonstrated that, after light exposure, the combination of both AlClPc and cisplatin compounds in the same MSN platform potentiate the toxic effect against HeLa cells in comparison to the control AlClPc-MSN and cisplatin-MSN materials. These results show the potential of using MSN platforms as nanocarriers for combination photodynamic and chemotherapies to treat cancer. PMID:28347122

  7. Capecitabine and cisplatin (XP) combination systemic chemotherapy in heavily pre-treated HER2 negative metastatic breast cancer.

    PubMed

    Lee, Jieun; Kim, Hyun Ho; Ro, Sang Mi; Yang, Ji Hyun

    2017-01-01

    After taxane and anthracycline failure, no standard chemotherapy regimen is established in metastatic breast cancer (MBC). Capecitabine and cisplatin (XP) combination shows promising results in gastrointestinal cancer, but there are relatively scarce data in MBC. We reviewed the clinical outcome of XP regimen in anthracycline and taxane resistant, heavily pretreated MBC patients. Between Jan. 2010 to Feb. 2016, 48 HER2 negative MBC patients who failed anthracycline and taxane based chemotherapy were enrolled. In 43.8% of patients, more than 4 regimens were administrated before XP. Thirty-four patients (70.8%) were hormone receptor (HR) positive MBC. Patients were treated with XP (capecitabine [2000mg/m2 per oral; day 1-14] plus cisplatin [60mg/m2 IV; day 1], every 3 weeks) regimen. Median progression-free survival (PFS) in total population was 4.33 months (range 1.1~33.57 months). HR positive patients showed trends for superior PFS compared to triple negative breast cancer (TNBC), without statistical significance (6.53 vs. 3.83 months, P = 0.168). In HR positive group, patients receiving 3 or less lines of chemotherapy showed superior PFS compared to others (10.1 vs. 3.0 months, P = 0.039). In multivariate analysis, HR positive patients receiving 3 or less lines of regimens still showed superior PFS (HR = 2.624, 95% CI; 1.071~6.43, P = 0.032). Most common toxicity was grade 3-4 neutropenia, without treatment-related deaths. XP combination regimen showed clinical benefit with tolerable toxicity in heavily pretreated patients, including HR positive patients. After anthracycline and taxane failure, early administration of XP regimen in selected patients may have improve clinical outcome in breast cancer.

  8. Capecitabine and cisplatin (XP) combination systemic chemotherapy in heavily pre-treated HER2 negative metastatic breast cancer

    PubMed Central

    Lee, Jieun; Kim, Hyun Ho; Ro, Sang Mi; Yang, Ji Hyun

    2017-01-01

    Purpose/Objective(s) After taxane and anthracycline failure, no standard chemotherapy regimen is established in metastatic breast cancer (MBC). Capecitabine and cisplatin (XP) combination shows promising results in gastrointestinal cancer, but there are relatively scarce data in MBC. We reviewed the clinical outcome of XP regimen in anthracycline and taxane resistant, heavily pretreated MBC patients. Materials/Methods Between Jan. 2010 to Feb. 2016, 48 HER2 negative MBC patients who failed anthracycline and taxane based chemotherapy were enrolled. In 43.8% of patients, more than 4 regimens were administrated before XP. Thirty-four patients (70.8%) were hormone receptor (HR) positive MBC. Patients were treated with XP (capecitabine [2000mg/m2 per oral; day 1–14] plus cisplatin [60mg/m2 IV; day 1], every 3 weeks) regimen. Results Median progression-free survival (PFS) in total population was 4.33 months (range 1.1~33.57 months). HR positive patients showed trends for superior PFS compared to triple negative breast cancer (TNBC), without statistical significance (6.53 vs. 3.83 months, P = 0.168). In HR positive group, patients receiving 3 or less lines of chemotherapy showed superior PFS compared to others (10.1 vs. 3.0 months, P = 0.039). In multivariate analysis, HR positive patients receiving 3 or less lines of regimens still showed superior PFS (HR = 2.624, 95% CI; 1.071~6.43, P = 0.032). Most common toxicity was grade 3–4 neutropenia, without treatment-related deaths. Conclusions XP combination regimen showed clinical benefit with tolerable toxicity in heavily pretreated patients, including HR positive patients. After anthracycline and taxane failure, early administration of XP regimen in selected patients may have improve clinical outcome in breast cancer. PMID:28234911

  9. Radiation enhanced efficiency of combined electromagnetic hyperthermia and chemotherapy of lung carcinoma using cisplatin functionalized magnetic nanoparticles.

    PubMed

    Babincová, M; Kontrisova, K; Durdík, S; Bergemann, C; Sourivong, P

    2014-02-01

    The effect of trimodality treatment consisting of hyperthermia, cisplatin and radiation was investigated in two non-small lung carcinoma cell lines with different sensitivities to cisplatin. Hyperthermia treatment was performed using heat released via Neél and Brown relaxation of magnetic nanoparticles in an alternating magnetic field. Radiation with dose 1.5 Gy was performed after 15 min electromagnetic hyperthermia and cisplatin treatment. Electromagnetic hyperthermia enhanced cisplatin-induced radiosensitization in both the cisplatin-sensitive H460 (viability 11.2 +/- 1.8 %) and cisplatin-resistant A549 (viability 14.5 +/- 2.3 %) lung carcinoma cell line. Proposed nanotechnology based trimodality cancer treatment may have therefore important clinical applications.

  10. MALDI-LTQ-Orbitrap mass spectrometry imaging for lipidomic analysis in kidney under cisplatin chemotherapy.

    PubMed

    Moreno-Gordaliza, Estefanía; Esteban-Fernández, Diego; Lázaro, Alberto; Humanes, Blanca; Aboulmagd, Sarah; Tejedor, Alberto; Linscheid, Michael W; Gómez-Gómez, M Milagros

    2017-03-01

    Imaging techniques for mapping molecular distributions in tissue sections can reveal valuable information on biomolecules involved in relevant biochemical processes. A method has been developed for comprehensive, reproducible and sensitive lipid imaging by matrix-assisted laser/desorption ionization-LTQ-Orbitrap mass spectrometry in kidney sections, showing the benefits of exact mass determination. Matrix deposition parameters for positive and negative lipid ion imaging using different matrices such as 2,5-dihydroxybenzoic acid (DHB), 9-aminoacridine (9-AA) or α-cyano-4-hydroxycinnamic acid (CHCA) have been optimized for the broadest detection and identification of renal lipids. The combination of 9-AA and DHB was found as the most suitable for negative and positive ion mode lipid imaging, respectively. Lipid mapping and related identification strategies and limitations have also been discussed. Production of 100-µm resolution images was proved to be enough for discerning lipid distribution in kidney substructures. Imaging reproducibility was assessed on parallel kidney slices with time. This method has been applied to the lipidomics analysis on kidney sections from rats treated with the antitumor drug cisplatin and compared to healthy control rats. Up to 66 different renal lipids out of 450 extracted ion images (mainly phospholipid species, in addition to sulfatides and cholesterol sulfate) have been found and identified showing a modified distribution pattern due to cisplatin-induced nephrotoxicity. These lipid species reflect either topographic, signaling or structural processes in damaged kidney and could potentially be used for nephrotoxicity assessment or as therapeutic targets. This is, to our knowledge, the first imaging lipidomics study for nephrotoxicity assessment of cisplatin chemotherapy.

  11. Comparing two lower-dose cisplatin programs for radio-chemotherapy of locally advanced head-and-neck cancers.

    PubMed

    Rades, Dirk; Seidl, Daniel; Janssen, Stefan; Strojan, Primoz; Karner, Katarina; Bajrovic, Amira; Hakim, Samer G; Wollenberg, Barbara; Schild, Steven E

    2017-02-01

    Radio-chemotherapy is a common treatment for locally advanced squamous cell head-and-neck cancers (LA-SCCHN). Cisplatin (100 mg/m(2)) every 3 weeks is very common but associated with considerable toxicity. Therefore, cisplatin programs with lower daily doses were introduced. There is a lack of studies comparing lower-dose programs. In this study, 85 patients receiving radio-chemotherapy with 20 mg/m(2) cisplatin on 5 days every 4 weeks (group A) were retrospectively compared to 85 patients receiving radio-chemotherapy with 30-40 mg/m(2) cisplatin weekly (group B). Groups were matched for nine factors including age, gender, performance score, tumor site, T-/N-category, surgery, hemoglobin before radio-chemotherapy, and radiation technique. One- and 3-year loco-regional control rates were 83 and 69 % in group A versus 74 and 63 % in group B (p = 0.12). One- and 3-year survival rates were 93 % and 73 % in group A versus 91 and 49 % in group B (p = 0.011). On multivariate analysis, survival was significantly better for group A (HR 1.17; p = 0.002). In groups A and B, 12 and 28 % of patients, respectively, did not receive a cumulative cisplatin dose ≥180 mg/m(2) (p = 0.016). Toxicity rates were not significantly different. On subgroup analyses, group A patients had better loco-regional control (p = 0.040) and survival (p = 0.005) than group B patients after definitive radio-chemotherapy. In patients receiving adjuvant radio-chemotherapy, outcomes were not significantly different. Thus, 20 mg/m(2) cisplatin on 5 days every 4 weeks resulted in better loco-regional control and survival in patients receiving definitive radio-chemotherapy and may be preferable for these patients. Confirmation of these results in a randomized trial is warranted.

  12. Pharmacokinetic evaluation of intrapleural perfusion with hyperthermic chemotherapy using cisplatin in patients with malignant pleural effusion.

    PubMed

    Sakaguchi, Hirozo; Ishida, H; Nitanda, H; Yamazaki, N; Kaneko, K; Kobayashi, Kunihiko

    2017-02-01

    Malignant pleural effusion (MPE) has a poor prognosis. Most patients are treated with tube thoracostomy and sclerotherapy, although its success rate is around 64%. We have investigated intrapleural perfusion with hyperthermic chemotherapy (IPHC) using cisplatin in a study with a pharmacokinetic evaluation. Patients with MPE, performance status of 0-1, possibility of good lung expansion and Cr<1.2mg/dL were treated with IPHC. The circuit was filled with 2000mL of normal saline containing cisplatin at a dose of 80mg/m(2). Under video-assisted thoracoscopic surgery, the thoracic cavity was filled and perfused at a speed of approximately 1L/min at a temperature of 43°C for 1h. Perfusion solution and plasma samples were periodically collected, and concentrations of protein-unbound (free) platinum, which was the active derivative of cisplatin, and total platinum were determined by flameless atomic absorption spectrometry. Twenty patients with MPE (8 lung cancers, 7 mesotheliomas, and 5 others) were enrolled in this study. Rate of free platinum concentration relative to total platinum concentration in perfusion solution after 1hr IPHC at 43°C was 61.1±12.9%. Area under curve (AUC) of free platinum in the pleural space was calculated to be 26.3μg/mLxh, resulting in complete control of pleural effusion for 3 months after IHPC in all cases (95% confidence interval: 83-100%). While, absorption rate of total platinum from the pleural space was 33.8±17.0% (27.4±13.6mg/m(2)), and the maximum concentration of total platinum in serum was low, 0.66±0.31μg/mL, resulting in controllable side effects; grade 1 renal toxicity: 6 patients, grade 1 emesis: 7 patients. IPHC with cisplatin showed favorable pharmacokinetic profiles for an optional treatment to control malignant pleural effusion. Copyright © 2016 The Author(s). Published by Elsevier B.V. All rights reserved.

  13. PROCLAIM: Randomized Phase III Trial of Pemetrexed-Cisplatin or Etoposide-Cisplatin Plus Thoracic Radiation Therapy Followed by Consolidation Chemotherapy in Locally Advanced Nonsquamous Non-Small-Cell Lung Cancer.

    PubMed

    Senan, Suresh; Brade, Anthony; Wang, Lu-Hua; Vansteenkiste, Johan; Dakhil, Shaker; Biesma, Bonne; Martinez Aguillo, Maite; Aerts, Joachim; Govindan, Ramaswamy; Rubio-Viqueira, Belén; Lewanski, Conrad; Gandara, David; Choy, Hak; Mok, Tony; Hossain, Anwar; Iscoe, Neill; Treat, Joseph; Koustenis, Andrew; San Antonio, Bélen; Chouaki, Nadia; Vokes, Everett

    2016-03-20

    The phase III PROCLAIM study evaluated overall survival (OS) of concurrent pemetrexed-cisplatin and thoracic radiation therapy (TRT) followed by consolidation pemetrexed, versus etoposide-cisplatin and TRT followed by nonpemetrexed doublet consolidation therapy. Patients with stage IIIA/B unresectable nonsquamous non-small-cell lung cancer randomly received (1:1) pemetrexed 500 mg/m(2) and cisplatin 75 mg/m(2) intravenously every 3 weeks for three cycles plus concurrent TRT (60 to 66 Gy) followed by pemetrexed consolidation every 3 weeks for four cycles (arm A), or standard therapy with etoposide 50 mg/m(2) and cisplatin 50 mg/m(2) intravenously, every 4 weeks for two cycles plus concurrent TRT (60 to 66 Gy) followed by two cycles of consolidation platinum-based doublet chemotherapy (arm B). The primary objective was OS. The study was designed as a superiority trial with 80% power to detect an OS hazard ratio of 0.74 with a type 1 error of .05. Enrollment was stopped early because of futility. Five hundred ninety-eight patients were randomly assigned (301 to arm A, 297 to arm B) and 555 patients (283 in arm A, 272 in arm B) were treated. Arm A was not superior to arm B in terms of OS (hazard ratio, 0.98; 95% CI, 0.79 to 1.20; median, 26.8 v 25.0 months; P = .831). Arm A had a significantly lower incidence of any drug-related grade 3 to 4 adverse events (64.0% v 76.8%; P = .001), including neutropenia (24.4% v 44.5%; P < .001), during the overall treatment period. Pemetrexed-cisplatin combined with TRT followed by consolidation pemetrexed was not superior to standard chemoradiotherapy for stage III unresectable nonsquamous non-small-cell lung cancer. © 2016 by American Society of Clinical Oncology.

  14. Prospective Pilot Study of Consolidation Chemotherapy With Docetaxel and Cisplatin After Concurrent Chemoradiotherapy for Advanced Head and Neck Cancer

    SciTech Connect

    Lee, Kyun Chan; Lee, Seok Ho; Lee, Yuna; Park, Se Hoon Park, Jinny; Cho, Eun Kyung; Shin, Dong Bok; Lee, Jae Hoon; Kim, Dong Young; Kim, Seon Tae

    2008-05-01

    Purpose: With the improvement concurrent chemoradiotherapy (CCRT) in the management of patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC), distant failures have become a more relevant problem in terms of survival. The primary objective of this Phase II study is to assess the feasibility of docetaxel and cisplatin consolidation after primary CCRT for patients with HNSCC. Methods and Materials: Patients with locoregionally advanced HNSCC received chemotherapy with three cycles of cisplatin, 100 mg/m{sup 2}, on Days 1, 22, and 43. Concurrent radiotherapy to the primary tumor and neck was given in a daily dose of 2 Gy to a total dose of 70-70.2 Gy over 7 weeks. After completion of CCRT, patients without evidence of disease progression received an additional four cycles of consolidation chemotherapy with docetaxel, 75 mg/m{sup 2}, and cisplatin, 75 mg/m{sup 2}, every 3 weeks. Results: Of 33 patients, 27 (81%) completed CCRT. After CCRT, three complete and 19 partial responses were recorded, giving an overall response rate of 67%. Of 19 patients who went to the consolidation phase, only 4 (21%) received all four cycles of docetaxel and cisplatin. Causes of failure of consolidation chemotherapy were toxicity in 11 patients, including three treatment-related deaths, and progression in 4 patients. Three patients died of sepsis during the consolidation phase. Median survival was 11 months for all patients and 8 months for those treated with consolidation chemotherapy. Conclusion: The poor compliance and high incidence of severe toxicities prompted no further evaluation of this consolidation chemotherapy after CCRT.

  15. [A case of pineoblastoma successfully treated with surgery, combined chemotherapy of cisplatin and etoposide, and radiotherapy].

    PubMed

    Akiyama, Y; Akiyama, Y; Kumai, J; Nishikawa, M

    1995-10-01

    A 5-year-old girl was admitted to another clinic because of vomiting and convulsions. She was brought to our clinic after a ventriculoperitoneal shunt was inserted. CT scan on admission in our clinic showed a tumor in the pineal region with tumoral hemorrhage. Tumor markers such as HCG, AFP, CEA, P-LAP were within normal range. A biopsy of the tumor was performed and the histological diagnosis was pineoblastoma. Her recovery was excellent and disseminated metastasis was not recognized. A subtotal removal of the tumor was performed through the occipital transtentorial approach. She had no neurological deficits after surgery. She then received two 5-day cycles of chemotherapy, consisting of intravenous administration of 20 mg/m2/day cisplatin and 60 mg/m2/day etoposide, and craniospinal radiotherapy. After these therapies, the tumor responded and disappeared completely. Follow-up radiographic investigations also demonstrated no abnormal evidence except for brain atrophy. She is attending a primary school without any problems. Pineoblastoma is quite rare and remarkably malignant. Hence, aggressive therapies including surgery, radiotherapy and chemotherapy is indicated for this tumor.

  16. Alternating chemotherapy with amrubicin plus cisplatin and weekly administration of irinotecan plus cisplatin for extensive-stage small cell lung cancer.

    PubMed

    Noro, Rintaro; Yoshimura, Akinobu; Yamamoto, Kazuo; Miyanaga, Akihiko; Mizutani, Hideaki; Minegishi, Yuji; Seike, Masahiro; Kubota, Kaoru; Kosaihira, Seiji; Hino, Mitsunori; Ando, Masahiro; Nomura, Koichiro; Okano, Tetsuya; Kobayashi, Kunihiko; Uematsu, Kazutsugu; Gemma, Akihiko

    2013-03-01

    A phase II study was conducted in order to determine the tumor efficacy and tolerance of alternating chemotherapy for extensive-stage small cell lung cancer (ED-SCLC). Twenty patients with previously-untreated ED-SCLC were enrolled in the study. At least four courses of chemotherapy consisting of alternation of two drug combinations were given: alternating cycles of amrubicin and cisplatin with weekly administration of irinotecan and cisplatin at 3- or 4-week intervals. The overall response rate was 85.0% (17/20). The median duration of overall survival and progression-free survival were 359 days and 227 days, respectively. Hematological toxicity was the main adverse event. Grade 3 or 4 neutropenia, thrombocytopenia and anemia were observed in 20 (100%), 4 (20%) and 6 (30%) patients, respectively. With regard to non-hematological adverse events, grade 3 or 4 anorexia, diarrhea, febrile neutropenia and infection were observed in 5 (25%), 2 (10%), 2 (10%) and 2 (10%) patients, respectively. No treatment-related death occurred during either regimen. The novel alternating non-cross-resistant chemotherapy was probably active against ED-SCLC and had acceptable toxicities. Further evaluation of this treatment for ED-SCLC in randomized phase III trials is warranted.

  17. Primary Concurrent Chemoradiation in Head and Neck Cancers with Weekly Cisplatin Chemotherapy: Analysis of Compliance, Toxicity and Survival.

    PubMed

    Iqbal, Muhammad Shahid; Chaw, Cheng; Kovarik, Josef; Aslam, Shahzeena; Jackson, Aaron; Kelly, John; Dobrowsky, Werner; Kelly, Charles

    2017-04-01

    Introduction Concurrent chemoradiation is the standard of care in inoperable locally advanced squamous cell head and neck cancers. The most widely accepted schedule of concomitant cisplatin is 100mg/m(2) given on a 3 weekly basis but the optimal regime is unknown. Objective The objective of this study is to assess the tolerability, compliance, and clinical outcomes of weekly cisplatin (40mg/m(2)). Methods During the period of January 2007-December 2009, we analyzed retrospectively 122 patients with histologically proven squamous cell carcinoma of head and neck (nasopharynx, oropharynx, larynx, hypopharynx, and oral cavity) treated with definitive chemoradiation. All patients received 63 Gy in 30 daily fractions with concomitant weekly cisplatin 40mg/m(2). We assessed treatment toxicities and patient compliance. We estimated overall survival using the Kaplan-Meier method. Results Sixty-eight percent of patients managed to complete all six cycles of chemotherapy while 87% of patients completed at least 5 cycles of weekly cisplatin. Incidence of grade 3/4 toxicity was as follows: mucositis 33%, dermatitis 41%, dysphagia 15%, mouth/neck pain 17%, neutropenia 2%, and renal impairment 3%. 53% patients required at least one hospital admission for symptom control. The 5-year overall survival rate was 60%. Conclusion Concurrent chemoradiotherapy using weekly cisplatin at 40mg/m(2) per week is an effective, well tolerated regimen allowing most patients to receive at least 5 cycles of chemotherapy. However, a phase III randomized control trial comparing the standard dose of 100mg/m(2) cisplatin tri-weekly with a weekly regimen is needed to establish the long term clinical outcome.

  18. Primary Concurrent Chemoradiation in Head and Neck Cancers with Weekly Cisplatin Chemotherapy: Analysis of Compliance, Toxicity and Survival

    PubMed Central

    Iqbal, Muhammad Shahid; Chaw, Cheng; Kovarik, Josef; Aslam, Shahzeena; Jackson, Aaron; Kelly, John; Dobrowsky, Werner; Kelly, Charles

    2016-01-01

    Introduction Concurrent chemoradiation is the standard of care in inoperable locally advanced squamous cell head and neck cancers. The most widely accepted schedule of concomitant cisplatin is 100mg/m2 given on a 3 weekly basis but the optimal regime is unknown. Objective The objective of this study is to assess the tolerability, compliance, and clinical outcomes of weekly cisplatin (40mg/m2). Methods During the period of January 2007–December 2009, we analyzed retrospectively 122 patients with histologically proven squamous cell carcinoma of head and neck (nasopharynx, oropharynx, larynx, hypopharynx, and oral cavity) treated with definitive chemoradiation. All patients received 63 Gy in 30 daily fractions with concomitant weekly cisplatin 40mg/m2. We assessed treatment toxicities and patient compliance. We estimated overall survival using the Kaplan-Meier method. Results Sixty-eight percent of patients managed to complete all six cycles of chemotherapy while 87% of patients completed at least 5 cycles of weekly cisplatin. Incidence of grade 3/4 toxicity was as follows: mucositis 33%, dermatitis 41%, dysphagia 15%, mouth/neck pain 17%, neutropenia 2%, and renal impairment 3%. 53% patients required at least one hospital admission for symptom control. The 5-year overall survival rate was 60%. Conclusion Concurrent chemoradiotherapy using weekly cisplatin at 40mg/m2 per week is an effective, well tolerated regimen allowing most patients to receive at least 5 cycles of chemotherapy. However, a phase III randomized control trial comparing the standard dose of 100mg/m2 cisplatin tri-weekly with a weekly regimen is needed to establish the long term clinical outcome.

  19. Successful Treatment of Pituitary Germinoma with Etoposide, Cisplatin, Vincristine, Methotrexate and Bleomycin Chemotherapy Without Radiotherapy.

    PubMed

    Scherz, Amina; Feller, Katrin; Berezowska, Sabina; Genitsch, Vera; Zweifel, Martin

    2017-06-01

    We report on the case of a 25-year-old man with pituitary germinoma. The patient had noticed polydipsia, reduced sexual function, and loss of body hair. Laboratory investigations confirmed panhypopituitarism including diabetes insipidus. Magnetic resonance imaging of the brain showed a 14×8.4 mm enhancing lesion of the pituitary stalk and histopathology of the neurosurgical biopsy confirmed pituitary germinoma. The patient was treated with 3 cycles of chemotherapy, consisting of 150 mg/m(2) etoposide and 75 mg/m(2) cisplatin, with the administration of intrathecal 12.5 mg methotrexate, on day one, alternating every 10 to 11 days with 1 mg/m(2) vincristine, 1,000 mg/m(2) methotrexate on day 1 and 30 mg/m(2) bleomycin on day 2. MRI scans showed lasting complete remission more than a year after completion of chemotherapy. Intracranial germinomas are exquisitely sensitive to radiation. However, due to concerns of side-effects (radiation-associated tumour, relapse outside the radiation field, mental and pituitary hormonal dysfunction), and after discussing both approaches carefully with the patient, the decision was made to treat his pituitary germinoma with chemotherapy alone. Further studies should address the question as to whether a modulated approach, using radiotherapy only as a salvage in patients with relapse, might result in a better overall outcome, given the potentially harmful long-term side-effects of radiotherapy to the brain. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  20. Stevens-Johnson Syndrome Patient Received Combination Chemotherapy Gemcitabine, Cisplatin, and 5-FU for Biliary Tract Cancer.

    PubMed

    Aznab, Mozaffar; Khazaei, Mansour

    2016-06-01

    Stevens-Johnson syndrome has been an acute, usually self-limiting disease of the skin and mucous membranes. This case report has presented an evidence of the development Stevens - Johnson syndrome associated with combination chemotherapy administration of 5FU, gemcitabin and cisplatin in a patient with biliary tract cancer. Our case was a 54-year-old woman patient, a case of biliary tract cancer who has developed more severe symptoms of Stevens-Johnson syndrome. Diagnosis has confirmed by skin biopsy of an affected area .The patient has improved with supportive care, and during 25 day occurred recovery. Although Stevens-Johnson syndrome has been a rare toxicity, physicians should pay a special attention to the monitoring of biliary tract cancer patients on combination chemotherapy with 5FU, cisplatin and gemcitabin.

  1. Hyperthermic intraperitoneal chemotherapy with cisplatin and paclitaxel in advanced ovarian cancer: a multicenter prospective observational study

    PubMed Central

    Coccolini, Federico; Campanati, Luca; Catena, Fausto; Ceni, Valentina; Jimenez Cruz, Jorge; Lotti, Marco; Magnone, Stefano; Napoli, Josephine; Rossetti, Diego; De Iaco, Pierandrea; Frigerio, Luigi; Pinna, Antonio; Runnebaum, Ingo; Ansaloni, Luca

    2015-01-01

    Objective Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been recently reported with favorable oncological outcomes as treatment of advanced epithelial ovarian cancer (EOC). The aim of this study was to demonstrate the feasibility of CRS+HIPEC with cisplatin and paclitaxel for the treatment of advanced EOC. Methods This is a prospective observational study of 54 patients, from April 2007 to October 2013, with primary or recurrent peritoneal carcinomatosis due to EOC. The mean age was 54.51±9.34. Thirty patients (59%) had primary EOC, and 24 patients (41%) had recurrent disease. Results Mean peritoneal cancer index was 10.11 (range, 0 to 28), complete cytoreduction (CC0) was achieved for 47 patients (87%), CC1 for seven patients (13%). Patients with suboptimal cytoreduction (CC2 and CC3) were not included in the study. The mean stay in intensive care unit was 4.73±5.51 days and the mean hospitalization time was 24.0±10.03 days. We did not observe any intraoperative death. Seven patients (13%) required additional operations. Three patients (5.6%) died within 30 days from the procedure. Severe complications were seen in 19 patients (35.2%). During the follow-up period, disease recurred in 33 patients (61.1%); the median disease-free survival time was 12.46 months and the median overall survival time was 32.91 months. Conclusion CRS+HIPEC with cisplatin and paclitaxel for advanced EOC is feasible with acceptable morbidity and mortality. Additional follow-up and further studies are needed to determine the effects of HIPEC on long term survival. PMID:25376916

  2. Preoperative induction chemotherapy with cisplatin and irinotecan for pathological N2 non-small cell lung cancer

    PubMed Central

    Date, H; Kiura, K; Ueoka, H; Tabata, M; Aoe, M; Andou, A; Shibayama, T; Shimizu, N

    2002-01-01

    We conducted a phase I/II study to investigate whether the surgical resection after induction chemotherapy with cisplatin and irinotecan was feasible and could improve the treatment outcome for patients with pathological N2 non-small cell lung cancer. Fifteen patients with stage IIIA non-small cell lung cancer having mediastinal lymph node metastases proved by mediastinoscopy were eligible. Both cisplatin (60 mg m−2) and irinotecan (50 mg m−2) were given on days 1 and 8. Patients received two cycles of chemotherapy after 3–4 weeks interval. Induction was followed by surgical resection in 4–6 weeks. Patients who had documented tumour regression after preoperative chemotherapy received two additional cycles of chemotherapy and other patients received radiotherapy postoperatively. After the induction chemotherapy, the objective response rate was 73%. All the 15 patients received surgical resection and complete resection was achieved in 11 (73%) patients. There was no operation-related death and one death due to radiation pneumonitis during postoperative radiotherapy. The median time from entry to final analysis was 46.5 months, ranging from 22 to 68 months. The 5-year survival rate was 40% for all the 15 patients and it was 55% for the 11 patients who underwent complete resection. We conclude that the surgical resection after induction chemotherapy with cisplatin and irinotecan is feasible, and associated with low morbidity and high respectability. British Journal of Cancer (2002) 86, 530–533. DOI: 10.1038/sj/bjc/6600117 www.bjcancer.com © 2002 Cancer Research UK PMID:11870532

  3. Role of ABCG2 expression driven by cisplatin in platinum-containing chemotherapy for gastric cancer

    PubMed Central

    Zhang, Qiang; Li, Kun; Xu, Jian-Hua; Zhao, Cheng-Gen; Gao, Qi; Wu, Bin; Liu, Xiao-Yan

    2013-01-01

    AIM: To investigate the relationship between increases in expression time of ABCG2 mRNA driven by cisplatin and efficacy of platinum-containing chemotherapy for gastric cancer. METHODS: Tumor specimens and normal control tissues were collected from 78 patients with gastric cancer treated from January 2008 to December 2011. Fresh tumor tissue obtained from the surgically resected specimens was tested within 6 h. Polymerase chain reaction products were run on 2% agarose gels and analyzed under ultraviolet light after ethidium bromide staining. Increases in ABCG2 mRNA expression time were assessed after cancer cells were incubated with cisplatin, and were divided into terciles and compared in relation to clinical outcomes. RESULTS: Among groups classified by expression time of ABCG2 mRNA, no significant differences in baseline clinical characteristics and pathological findings were detected. The median overall time was 14.2 (95%CI: 9.7-18.6), 11.4 (95%CI: 6.3-16.5) and 8.1 (95%CI: 5.4-10.8) in patients with low, intermediate and high increases in ABCG2 mRNA expression times (P < 0.05), respectively. Median survival associated with performance status and tumor node metastasis (TNM) stage showed a similar trend, with longer survival and higher risk for mortality associated with lower performance status score and TNM stage. In a multivariate analysis for survival with Cox proportional-hazards model, increased ABCG2 mRNA expression time was an independent predictor for overall survival. Overall survival was longer with increased ABCG2 mRNA expression times ≤ 0.71 than increased ABCG2 mRNA expression times > 0.71, with a hazard ratio for death of 0.855 (95%CI: 0.615-0.962, P = 0.038). CONCLUSION: Increased ABCG2 mRNA expression time driven by cisplatin is associated with survival of gastric cancer patients, and this may help modify the therapeutic strategies. PMID:24151392

  4. [A case of unresectable advanced gastric cancer responding remarkably to combined chemotherapy with 5-fluorouracil and low-dose cisplatin].

    PubMed

    Yasumoto, K; Iwamoto, M; Hoshiko, M; Kawabata, S; Fujii, T; Morimatsu, M; Takeda, J; Kakegawa, T

    1995-11-01

    A 62-year-old male patient complaining epigastralgia was diagnosed as having Borrmann type 2 gastric concer (por). The primary lesion was unresectable, so the patient was treated by combined chemotherapy with 5-fluorouracil and low-dose cisplatin for 4 weeks, which resulted in the disappearance of primary tumor and a remarkable reduction of metastatic lymph nodes. The patient has a good quality of life without any sign of recurrence now.

  5. Phase II trial of biweekly docetaxel, cisplatin, and 5-fluorouracil chemotherapy for advanced esophageal squamous cell carcinoma.

    PubMed

    Tanaka, Yoshihiro; Yoshida, Kazuhiro; Yamada, Atsuko; Tanahashi, Toshiyuki; Okumura, Naoki; Matsuhashi, Nobuhisa; Yamaguchi, Kazuya; Miyazaki, Tatsuhiko

    2016-06-01

    The prognosis of esophageal cancer patients is still unsatisfactory. Although a docetaxel, cisplatin, and 5-Fu (DCF) regimen has been reported, it is often difficult to accomplish because of severe toxicity. Therefore, we developed a new biweekly DCF (Bi-DCF) regimen and previously reported the recommended dose in a phase I dose-escalation study. We then performed a phase II study of Bi-DCF for advanced esophageal squamous cell carcinoma (SCC). Patients with clinical stage II/III were eligible. Patients received 2 courses of chemotherapy: docetaxel 35 mg/m(2) with cisplatin 40 mg/m(2) on days 1 and 15 and 400 mg/m(2) 5-fluorouracil on days 1-5 and 15-19 every 4 weeks. After completion of the chemotherapy, patients received esophagectomy. The primary endpoint was the completion rate of protocol treatment. Thirty-two patients were enrolled. The completion rate of protocol treatment (completion of two courses of preoperative chemotherapy and R0 surgery) was 100 %. During chemotherapy, the most common grade 3 or 4 toxicities were neutropenia (31.3 %). No treatment-related death was observed, and the incidence of operative morbidity was tolerable. The overall response rate after the chemotherapy was 90.3 %. This Bi-DCF regimen was well tolerated and highly active. This trial was registered with the University Hospital Medical Information Network (No. UMIN 000014625).

  6. Nimotuzumab combined with gemcitabine and cisplatin as second-line chemotherapy for advanced non-small-cell lung cancer.

    PubMed

    Wang, Hua-Qing; Ren, Yangang; Qian, Zheng-Zi; Fu, Kai; Zhang, Hui-Lai; Li, Wei; Hou, Yun; Zhou, Shi-Yong; Hao, Xi-Shan; Xie, Cong-Hua

    2012-02-01

      To evaluate the efficacy and safety of nimotuzumab combined with gemcitabine and cisplatin as second-line chemotherapy for advanced non-small-cell lung cancer (NSCLC) and to investigate the association of the status of KRAS gene mutation and epidermal growth factor receptor (EGFR) genotype with clinical outcome.   Twenty-eight patients with advanced NSCLC were enrolled in this single center, uncontrolled pilot clinical study. All the patients developed drug resistance or disease progression after first-line chemotherapy of either a docetaxel + cisplatin regimen or a vinorelbine + cisplatin regimen and then received nimotuzumab combined with gemcitabine and cisplatin as second-line chemotherapy. Eight cases were stage IIIB and 20 were stage IV. An i.v. dosage regimen of 200 mg of nimotuzumab was given as a single dose, injected into the patient at days 1, 8 and 15; i.v. gemcitabine was injected at a dose of 1000 mg/m(2) at days 1 and 8 and cisplatin (25 mg/m(2) i.v.) at days 1, 2 and 3. Each patient received four or more therapeutic cycles. The efficacy and toxic reactions were evaluated, as well as time to progression and overall survival.   In total, 28 patients with advanced NSCLC received 101 therapeutic cycles. The mean cycle number was 3.6. Median time to progression was 4.9 (2.5-6.5) months; median overall survival and 1-year survival rate were 9.8 months and 48.5%, respectively. There was one case of complete response, six cases of partial response, 11 cases of stable disease and 10 cases of progressive disease. Response rate was 25%, and clinical benefit rate was 64.3%. Major toxic reactions were bone marrow suppression and gastrointestinal reaction. Only one patient developed grade I acneiform eruption.   Nimotuzumab combined with gemcitabine and cisplatin as second-line chemotherapy for advanced NSCLC was active and well-tolerated in this setting. Patients with EGFR amplification and KRAS gene wild type had a better prognosis. Prospective

  7. [Cisplatin and vinca alkaloid combination chemotherapy of advanced non-small-cell lung cancer in the aged].

    PubMed

    Teramoto, S; Nagase, T; Fukuchi, Y; Ishida, K; Yamaoka, M; Matsuse, T; Jo, C; Orimo, H

    1990-11-01

    Fifteen patients aged over 65 years of age with advanced non-small-cl lung cancer (mean age = 70.7, stage IIIb: IV = 4:11) were treated with combination chemotherapy consisting of Cisplatin (50 or 80 mg/m2) and a vinca-alkaloid (Vindesine 3 mg/m2 or Etoposide 80 mg/m2). The effectiveness and side effects of this cisplatin therapy in different combinations of vinca-alkaloid regimens (Vindesine vs Etoposide) were examined. The mean dose of Cisplatin in the Etoposide combination group (75.2 mg/m2) was significantly higher than that in the Vindesine combination group (54.3 mg/m2) (p less than 0.01). A notable reduction the tumor size was observed in 25% of the Etoposide group, only. The 6-month survival rate and one-year survival rate were respectively 85.7%, 57.1% in the Vindesine + Cisplatin group, and 87.5%, 50% in the Etoposide + Cisplatin group. The common side effects were nausea, vomiting, anorexia, and alopecia. These symptoms were either alleviated by antiemetic drugs or followed by spontaneous recovery. Leucopenia, anemia and thrombocytopenia were found in both groups, and there was no difference in the time course of myelosuppression between the two groups. The extent of nephrotoxicity was assessed by creatinine clearance rate. Its decrease in the Vindesine group (60.1----38.9 ml/min) was higher than that in the Etoposide group (64.9----48.9 ml/min), while there was no significant change in BUN, serum creatinine and urine NAG between the two groups. There were no cases in which chemotherapy schedules had to be interrupted due to myelosuppression and nephrotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. A safe and effective dose of cisplatin in hepatic arterial infusion chemotherapy for hepatocellular carcinoma

    PubMed Central

    Osaki, Akihiko; Suda, Takeshi; Kamimura, Kenya; Tsuchiya, Atsunori; Tamura, Yasushi; Takamura, Masaaki; Igarashi, Masato; Kawai, Hirokazu; Yamagiwa, Satoshi; Aoyagi, Yutaka

    2013-01-01

    Cisplatin (CDDP) is an anticancer agent that is commonly used in hepatic arterial infusion (HAI) chemotherapy for hepatocellular carcinoma (HCC). This study aimed to clarify the safe and effective dose of CDDP in HAI for HCC. The hypervascular area was measured in 42 HCCs before and after HAI with CDDP. Serum platinum concentration was quantified in the peripheral and/or middle hepatic veins by atomic absorption spectrometry. The relation between the HCC response and CDDP dose was statistically analyzed. The multiple HCC nodules in an individual case generally demonstrated the same response to CDDP. The free-platinum concentration stayed relatively constant in the hepatic vein during HAI followed by a rapid decline, while total-platinum gradually increased then slowly disappeared over several days. After CDDP-HAI, 15 HCCs shrunk and 27 HCCs grew. The reduction rate in the shrunken nodules was tended to be correlated with CDDP dose after standardization with the target liver volume. On the other hand, the growth rate of the enlarged HCCs was significantly correlated with CDDP dose after normalization with creatinine clearance. These data support a recommendation of CDDP-HAI infusion where the amount of CDDP (mg) administered is less than patient creatinine clearance (mL/min/1.73 m2) upon an assumption of HCC doubling time of 90 days, and the targeted liver is smaller than 200 times the CDDP dose (mg). A further analysis is required to define appropriate injection speeds. PMID:24133631

  9. Effect of Concurrent High-Dose Cisplatin Chemotherapy and Conformal Radiotherapy on Cervical Esophageal Cancer Survival

    SciTech Connect

    Huang Shaohui; Lockwood, Gina; Brierley, James; Cummings, Bernard; Kim, John; Wong, Rebecca; Bayley, Andrew; Ringash, Jolie

    2008-07-01

    Purpose: To determine whether a change in treatment policy to conformal, elective nodal radiotherapy and concurrent high-dose cisplatin improved survival for cervical esophageal cancer patients. Methods and Materials: All cervical esophageal cancer patients treated between 1997 and 2005 were restaged (1983 American Joint Committee on Cancer criteria). Patients treated before 2001 (previous cohort [PC]) were compared with those treated from 2001 onward (recent cohort [RC]). The PC institutional chemoradiotherapy protocol was 54 Gy in 20 fractions within 4 weeks, with 5-fluorouracil (1,000 mg/m{sup 2}) on Days 1-4 and either mitomycin C (10 mg/m{sup 2}) or cisplatin (75 mg/m{sup 2}) on Day 1. The RC institutional chemoradiotherapy protocol was conformal radiotherapy, 70 Gy in 35 fractions within 7 weeks, to the primary tumor and elective nodes, with high-dose cisplatin (100 mg/m{sup 2}) on Days 1, 22, and 43. Results: The median follow-up was 3.1 years (PC, 8.1 and RC, 2.3). Of 71 patients (25 women and 46 men), 21 of 29 in the PC and 29 of 42 in the RC were treated curatively (curative subgroup, n = 50). Between the two groups, no differences in overall survival or locoregional relapse-free survival were seen. The overall survival rate at 2 and 5 years was 35% (range, 24-47%) and 21% (range, 12-32%) in the whole group and 46% (range 32-60%) and 28% (range, 15-42%) in the curative group, respectively. In the curative group, no statistically significant prognostic factors were found. Trends toward better locoregional relapse-free survival were seen in women (2-year rate, 73% vs. for men, 36%; p = 0.08) and in patients aged >64 years (2-year rate, 68% vs. age {<=}64 years, 34%; p = 0.10). Conclusion: No survival improvement could be demonstrated after changing the treatment policy to high-dose cisplatin-based, conventionally fractionated conformal chemoradiotherapy. Female gender and older age might predict for better outcomes.

  10. A phase I study of combination S-1 plus cisplatin chemotherapy with concurrent thoracic radiation for locally advanced non-small cell lung cancer.

    PubMed

    Chikamori, Kenichi; Kishino, Daizo; Takigawa, Nagio; Hotta, Katsuyuki; Nogami, Naoyuki; Kamei, Haruhito; Kuyama, Shoichi; Gemba, Kenichi; Takemoto, Mitsuhiro; Kanazawa, Susumu; Ueoka, Hiroshi; Segawa, Yoshihiko; Takata, Saburo; Tabata, Masahiro; Kiura, Katsuyuki; Tanimoto, Mitsune

    2009-07-01

    A combination of S-1, a newly developed oral 5-fluorouracil derivative, and cisplatin is reported to show anti-tumour activity against advanced non-small cell lung cancer (NSCLC). Because S-1 shows synergistic effects with radiation, we conducted a phase I study to evaluate the maximum tolerated doses (MTDs), recommended doses (RDs), and dose-limiting toxicities (DLTs) of cisplatin and S-1 when combined with concurrent thoracic radiation (total dose of 60 Gy with 2 Gy per daily fraction) in patients with locally advanced NSCLC. Chemotherapy consisted of two 4-week cycles of cisplatin administered on days 1 and 8, and S-1 administered on days 1-14. S-1/cisplatin dosages (mg/m(2)/day) were escalated as follows: 60/30, 60/40, 70/40, 80/40 and 80/50. Twenty-two previously untreated patients were enrolled. The MTDs and RDs for S-1/cisplatin were 80/50 and 80/40, respectively. DLTs included febrile neutropaenia, thrombocytopaenia, bacterial pneumonia and delayed second cycle of chemotherapy. No patient experienced radiation pneumonitis>grade 2 and only one patient experienced grade 3 radiation oesophagitis. The overall response rate was 86.4% with a median survival time of 24.4 months. These results indicate that combination cisplatin-S-1 chemotherapy with concurrent thoracic radiation would be a feasible treatment option and a phase II study is currently under way.

  11. A randomised phase II study of combination chemotherapy with epirubicin, cisplatin and capecitabine (ECX) or cisplatin and capecitabine (CX) in advanced gastric cancer.

    PubMed

    Yun, Jina; Lee, Jeeyun; Park, Se Hoon; Park, Joon Oh; Park, Young Suk; Lim, Ho Yeong; Kang, Won Ki

    2010-03-01

    Both cisplatin/capecitabine (CX) and epirubicin plus CX (ECX) have clearly demonstrated efficacy against advanced gastric cancer (AGC). Chemotherapy-naïve patients with histologically confirmed, measurable AGC were randomised to receive CX (cisplatin 75mg/m(2) iv on day 1 and capecitabine 1000mg/m(2) bid po on days 1-14) or ECX (epirubicin 50mg/m(2) plus CX) every 3weeks. The primary endpoint was progression-free survival (PFS). Of the 91 registered patients, 45 patients were treated with CX and 44 with ECX. A total of 241 CX (median, 6; range, 1-12) and 201 ECX (median, 5; range, 1-11) cycles were delivered. Treatment duration was similar for both arms (4.4 for CX versus 4.2months for ECX). There was no relevant difference in the occurrence of overall grade 3 or 4 toxicities between the CX and ECX arms (80% versus 78%, respectively; P=0.516). However, none in the CX and 12% in the ECX arm discontinued treatment because of toxicity. There were no significant differences in therapeutic efficacy between CX and ECX with respect to the response rate (38% versus 37%, respectively) and PFS (6.4 versus 6.5months). Both CX and ECX appear to be active as first-line chemotherapy for AGC, and the safety profiles are acceptable. Given the comparable efficacy results, CX could be a reasonable standard chemotherapy for untreated AGC patients. Copyright 2009 Elsevier Ltd. All rights reserved.

  12. Evaluating the Effect of Zingiber Officinalis on Nausea and Vomiting in Patients Receiving Cisplatin Based Regimens

    PubMed Central

    Fahimi, Fanak; Khodadad, Kian; Amini, Somayeh; Naghibi, Farzaneh; Salamzadeh, Jamshid; Baniasadi, Shadi

    2011-01-01

    Ginger, the rhizome of Zingiber officinalis, has long been used as herbal medicine for its antiemetic effect. For evaluating the effect of zingiber officinalis on nausea and vomiting (N and V) in patients receiving cisplatin based regimens, a randomized double-blind placebo-controlled cross-over clinical trial was carried out in patients receiving cisplatin in combination with other chemotherapeutic agents. The patients were randomly assigned to receive ginger capsules (rhizome of zingiber officinalis) or placebo in their first cycle of the study. All patients received standard antiemetics for chemotherapy induced nausea and vomiting (CINV). The patients were crossed-over to receive ginger or placebo in their next cycle of chemotherapy. Among 36 eligible patients who received both cycles of treatment, there were no difference in prevalence, severity, and duration of both acute and delayed N and V. Addition of ginger to the standard antiemetic regimen has shown no advantage in reducing acute and delayed N and V in patients with cisplatin-based regimen in this study. PMID:24250368

  13. Enhancement of Aerosol Cisplatin Chemotherapy with Gene Therapy Expressing ABC10 protein in Respiratory System

    PubMed Central

    Hohenforst-Schmidt, Wolfgang; Zarogoulidis, Paul; Linsmeier, Bernd; Kioumis, Ioannis; Li, Qiang; Huang, Haidong; Sachpatzidou, Despoina; Lampaki, Sofia; Organtzis, John; Domvri, Kalliopi; Sakkas, Leonidas; Zachariadis, George A.; Archontas, Konstantinos N.; Kallianos, Anastasios; Rapti, Aggeliki; Yarmus, Lonny; Zarogoulidis, Konstantinos; Brachmann, Johannes

    2014-01-01

    Inhaled therapy for lung cancer is a local form of treatment. Currently inhaled non-specific cytotoxic agents have been evaluated as a future treatment for local disease control and distant metastasis control. There are few information regarding the influence of local transporters and gene expression of the respiratory epithelium to the absorption of administered drugs. In the current work we used adenoviral-type 5(dE1/E3) (Cytomegalovirus promoter) with human ABCA10 transgene (Ad-h-ABCA10) purchased from Vector Labs® in order to investigate whether gene therapy can be used as a pre-treatment to enhance the efficiency of inhaled cisplatin. We included the following groups to our work: a) control, b) aerosol vector, c) aerosol vector plus cisplatin, d) aerosol cisplatin, e) intratumoral cisplatin administration, f) intratumoral vector plus cisplatin administration. The results indicate that the aerosol cisplatin group had a long term survival with the intratumoral cisplatin group following. The enhancement of the ABCA family locally to the respiratory system prior to the aerosol cisplatin administration can be used safely and efficiently. Future treatment design of local therapies should include the investigation of local transporters and genes. PMID:24723977

  14. Role of the Human High-Affinity Copper Transporter (hCtr1) in Copper Homeostasis Regulation and Cisplatin Sensitivity in Cancer Chemotherapy

    PubMed Central

    Kuo, Macus Tien; Fu, Siqing; Savaraj, Niramol; Chen, Helen H. W.

    2012-01-01

    The high-affinity copper transporter (Ctr1) (SCLC31A1) plays an important role in regulating Cu homeostasis because copper (Cu) is an essential micronutrient and Cu deficiency is detrimental to many important cellular functions but excess Cu is toxic. Recent research has revealed that human Cu homeostasis is tightly controlled by interregulatory circuitry involving Cu, Sp1 and hCtr1. This circuitry uses Sp1 transcription factor as a Cu sensor in modulating hCtr1 expression which in turn controls cellular Cu and Sp1 levels in a three-way mutual regulatory loop. Posttranslational regulation of hCtr1 expression by Cu stresses has also been described in the literature. Because hCtr1 can also transport platinum (Pt) drugs, this finding underscores the important role of hCtr1 in Pt drug sensitivity in cancer chemotherapy. Consistent with this notion is the findings that elevated hCtr1 expression was associated with favorable treatment outcomes in cisplatin-based cancer chemotherapy. Moreover, cultured cell studies demonstrated that elevated hCtr1 expression can be induced by depleting cellular Cu levels, resulting in enhanced cisplatin uptake and its cell killing activity. A phase 1 clinical trial using a combination of trientine (a Cu chelator) and carboplatin has been performed with encouraging results. This review discusses new insights into the role of hCtr1 in regulating Cu homeostasis and explains how modulating cellular Cu availability could influence treatment efficacy in platinum-based cancer chemotherapy through hCtr1 regulation. PMID:22962276

  15. Genetic variants in TPMT and COMT are associated with hearing loss in children receiving cisplatin chemotherapy.

    PubMed

    Ross, Colin J D; Katzov-Eckert, Hagit; Dubé, Marie-Pierre; Brooks, Beth; Rassekh, S Rod; Barhdadi, Amina; Feroz-Zada, Yassamin; Visscher, Henk; Brown, Andrew M K; Rieder, Michael J; Rogers, Paul C; Phillips, Michael S; Carleton, Bruce C; Hayden, Michael R

    2009-12-01

    Cisplatin is a widely used and effective chemotherapeutic agent, although its use is restricted by the high incidence of irreversible ototoxicity associated with it. In children, cisplatin ototoxicity is a serious and pervasive problem, affecting more than 60% of those receiving cisplatin and compromising language and cognitive development. Candidate gene studies have previously reported associations of cisplatin ototoxicity with genetic variants in the genes encoding glutathione S-transferases and megalin. We report association analyses for 220 drug-metabolism genes in genetic susceptibility to cisplatin-induced hearing loss in children. We genotyped 1,949 SNPs in these candidate genes in an initial cohort of 54 children treated in pediatric oncology units, with replication in a second cohort of 112 children recruited through a national surveillance network for adverse drug reactions in Canada. We identified genetic variants in TPMT (rs12201199, P value = 0.00022, OR = 17.0, 95% CI 2.3-125.9) and COMT (rs9332377, P value = 0.00018, OR = 5.5, 95% CI 1.9-15.9) associated with cisplatin-induced hearing loss in children.

  16. Chemotherapy with gemcitabine plus cisplatin in patients with advanced biliary tract carcinoma at Chang Gung Memorial Hospital: a retrospective analysis.

    PubMed

    Wu, Chiao-En; Hsu, Hung-Chih; Shen, Wen-Chi; Lin, Yang-Chung; Wang, Hung-Ming; Chang, John Wen-Chen; Chen, Jen-Shi

    2012-01-01

    A gemcitabine-cisplatin combination is a standard treatment option for patients with advanced biliary tract carcinoma (BTC). We assessed the efficacy and safety of this regimen at Chang Gung Memorial Hospital. Between April 2009 and December 2010, 30 chemotherapy-naïve patients (13 men and 17 women; median age: 61.5 years) with advanced BTC were retrospectively analyzed. Treatment consisted of gemcitabine (Gemmis(®); TTY, Taipei, Taiwan) 1000 mg/m(2), followed by cisplatin 30 mg/m(2) on days 1 and 8 every 3 weeks. Tumor response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria every 2-3 cycles. The toxicity was assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3. At the end of July, 2011, 27 patients were evaluated using the RECIST criteria. According to the intent to treat analysis of response, 5 patients (16.7%) had a partial response, 10 patients (33.3%) had stable disease and 12 patients (40.0%) had progressive disease. The median time to progression (TTP) and median overall survival (OS) of the 30 patients were 4.8 months and 13.4 months, respectively. The patients with biliary obstruction requiring drainage before treatment had a significantly shorter OS than those without biliary obstruction (p = 0.02) even though the TTP showed no statistically significant difference (p = 0.69) between groups. The major grade III/IV adverse events in the 30 patients included infection (n = 8, 26.7%), anemia (n = 5, 16.7%), neutropenia (n = 4, 13.3%), and elevated alanine aminotransferase (n = 2, 6.7%). There were no treatment-related deaths. Gemcitabine plus cisplatin is a feasible chemotherapy regimen with manageable toxicity in patients with advanced BTC. Maintaining good biliary drainage is essential for these patients.

  17. Doxorubicin-cisplatin chemotherapy for high-grade nonosteogenic sarcoma of bone. Comparison of treatment and control groups

    PubMed Central

    Waddell, Andrea E.; Davis, Aileen M.; Ahn, Henry; Wunder, Jay S.; Blackstein, Martin E.; Bell, Robert S.

    1999-01-01

    Objective To evaluate the role of chemotherapy with a combination of doxorubicin (adriamycin) and cisplatin in high-grade, nonosteogenic, non-Ewing’s sarcoma (non-OSA) of bone. Design A case series comparison with a literature-derived control group. Setting A university-affiliated tertiary care centre. Patients Thirty patients with a diagnosis of non-OSA. Of these, 8 had low-grade disease (grade 1 or 2) and 22 had high-grade disease (grade 3). Eleven of the 22 with high-grade disease had malignant fibrous histiocytoma. Seventeen patients with nonmetastatic high-grade non-OSA were compared with a literature cohort of 37 patients who met the eligibility criteria of nonmetastatic, high-grade non-OSA treated with surgery, with or without radiotherapy. The mean follow-up was 25.2 months. Interventions Eight patients with low-grade tumour underwent surgery alone; 22 patients with high-grade tumour underwent surgery and 6 courses of adriamycin (75 mg/m2 every 3 weeks) and cisplatin (100 mg/m2 every 3 weeks). Main outcome measures Disease-free survival and overall survival in those with high-grade tumours treated with or without chemotherapy. Results Of 8 patients who had low-grade tumours and underwent surgery alone, 3 had systemic relapse. Of the 22 having high-grade tumours, 4 did not receive chemotherapy because of age and comorbid conditions. Of the other 18, 13 received 3 courses of chemotherapy preoperatively and 3 courses postoperatively, 4 received all 6 courses postoperatively and 1 received all chemotherapy preoperatively to treat metastatic disease. In the 17-patient cohort used for comparison with the literature control group, disease-free survival was 57% at a mean follow-up of 25.6 months and overall survival was 57% at a mean follow-up of 30.1 months. In the control group, disease-free survival was 16% at a mean follow-up of 20.9 months and overall survival was 26% at a mean follow-up of 29.9 months. These differences are significant: p = 0.0000, χ2 = 41

  18. Inoperable nonmetastatic squamous cell carcinoma of the esophagus managed by concomitant chemotherapy (5-fluorouracil and cisplatin) and radiation therapy

    SciTech Connect

    Seitz, J.F.; Giovannini, M.; Padaut-Cesana, J.; Fuentes, P.; Giudicelli, R.; Gauthier, A.P.; Carcassonne, Y. )

    1990-07-15

    Thirty-five patients with nonmetastatic squamous cell carcinoma of the esophagus were treated with chemotherapy (5-fluorouracil, cisplatin) and concomitant split-course radiation therapy. All of the patients presented with dysphagia. Treatment consisted of two courses of chemotherapy with 5-FU (1 g/m2/day in continuous infusion for 5 days (days 1 to 5 and days 29 to 33) ) and cisplatin (70 mg/m2 intravenous bolus at days 2 and 30). Radiation therapy was concomitant in two courses delivering 20 Gy in 5 days (days 1 to 5 and days 29 to 33). On the first day of treatment, endoscopic peroral dilation or Nd-YAG laser therapy was usually carried out. At the end of the treatment, all of the patients were capable of oral nutrition. Histoendoscopic confirmation was made 8 weeks after the beginning of the therapy. Twenty-five of the 35 patients had a complete response with negative biopsy findings. There was only one serious complication (fatal myelosuppression) in the only patient who received more than two courses of chemotherapy. Sixteen patients died and 19 were still alive at 3 to 42 months after the beginning of treatment. Overall median survival for the 35 patients is 17 months. Actuarial survival was 55 +/- 18% at 1 year and 41 +/- 21% at 2 years. The median survival of the Stage I and II patients is 28 months. These results confirm that concomitant chemoradiotherapy is capable of producing a very high histoendoscopic complete response rate and improved 1-year and 2-year survival. The use of concentrated split-course radiotherapy enabled the authors to reduce the total length of the treatment to two periods of 5 days, with results that are similar to previous studies using classic radiotherapy for a 5-week to 7-week period.

  19. Hepatic arterial infusion chemotherapy using fluorouracil, epirubicin, and mitomycin C for patients with liver metastases from gastric cancer after treatment failure of systemic S-1 plus cisplatin.

    PubMed

    Seki, Hiroshi; Ohi, Hiroyuki; Ozaki, Toshirou; Yabusaki, Hiroshi

    2016-07-01

    For patients with liver metastases from gastric cancer (LMGC), combination chemotherapy with fluoropyrimidines and platinum agents has been recognized as standard treatment. However, the prognosis of hepatic progression after first-line treatment failure remains poor. When hepatic progression occurs, hepatic arterial infusion (HAI) chemotherapy may be helpful for preventing disease progression. To retrospectively assess the feasibility and efficacy of HAI chemotherapy using 5-fluorouracil, epirubicin, and mitomycin C (FEM) for patients with LMGC after failure of systemic S-1 plus cisplatin. We reviewed the records of patients who received HAI chemotherapy using FEM for LMGC that progressed during systemic S-1 plus cisplatin treatment while extrahepatic disease was decreased or did not appear. HAI chemotherapy was given as second-line therapy using 5-fluorouracil (330 mg/m(2) weekly), epirubicin (30 or 40 mg/m(2) every 4 weeks), and mitomycin C (2.7 mg/m(2) biweekly). Fourteen patients were analyzed. Toxicity of HAI chemotherapy was generally mild. The objective response rate was 42.9%, including a complete response rate of 14.3%. Median times to hepatic and extrahepatic progression were 9.2 and 7.4 months, respectively. Of 12 patients with documented progression after HAI chemotherapy, 10 patients (83.3%) received additional treatment, including irinotecan or taxanes. Overall, median survival was 12.7 months. Our findings suggest that HAI chemotherapy using FEM is a feasible and effective treatment for patients with LMGC after failure of systemic S-1 plus cisplatin. HAI chemotherapy employed in the second-line setting is useful for achieving long-term disease control of LMGC. © The Foundation Acta Radiologica 2015.

  20. A randomized study of cisplatin and 5-FU hepatic arterial infusion chemotherapy with or without adriamycin for advanced hepatocellular carcinoma.

    PubMed

    Song, Myeong Jun; Bae, Si Hyun; Chun, Ho Jong; Choi, Jong Young; Yoon, Seung Kew; Park, Jun Young; Han, Kwang Hyub; Kim, Young Seok; Yim, Hyung Joon; Um, Soon Ho; Chung, Woo Jin; Hwang, Jae Seok; Cho, Sung-Bum; Eun, Jong Ryul

    2015-04-01

    This multicenter, randomized, open-labeled, clinical trial evaluated the efficacy and safety of cisplatin/5-fluorouracil (5-FU) hepatic arterial infusion chemotherapy (CF-HAIC) versus adriamycin adding to CF-HAIC (ACF-HAIC) in advanced HCC patients. Fifty-six patients with advanced HCC were randomized to two treatment groups: (1) CF-HAIC group [n = 29, 5-FU, 500 mg/m(2) on days 1-3, and cisplatin, 60 mg/m(2) on day 2] and (2) ACF-HAIC group [n = 27, adriamycin, 50 mg/m(2) on day 1, 5-FU, 500 mg/m(2) on days 1-3, and cisplatin, 60 mg/m(2) on day 2] every 4 weeks via an implantable port system. Primary efficacy endpoint was overall survival (OS). Treatment response and time to progression were secondary endpoints. Treatment response rates did not differ significantly between the two treatment groups. Time to progression (5.4 vs. 5.8 months, P = 0.863) and OS (11.1 vs. 8.8 months, P = 0.448) were not significantly different. When the factors affecting patient OS were analyzed, disease control rate [P < 0.001, HR 6.437 (95% CI 2.580-16.064)] was independently associated with OS. Age (≥60 years) and serum AFP level (≥200 ng/dL) also were significant factors for OS [P = 0.007, HR 4.945 (95% CI 1.543-15.850), P = 0.048, HR 2.677 (95% CI 1.010-7.095), respectively]. Grade 4 treatment-related toxicity and mortality was not observed in both groups. Although both HAIC regimens are safe and effective in patients with advanced HCC, HAIC adding adriamycin did not show delayed tumor progression and survival benefit compared to CF-HAIC in advanced HCC.

  1. ERCC1 Expression in Metastatic Triple Negative Breast Cancer Patients Treated with Platinum-Based Chemotherapy

    PubMed

    EL Baiomy, Mohamed Ali; El Kashef, Wagdi F

    2017-02-01

    Background: Possible targeted therapies for metastatic triple negative breast cancer (TNBC) include cytotoxic chemotherapy that causes interstrand breaks (platinum-based drugs). The excision repair cross-complementation 1 (ERCC1) enzyme plays an essential role in the nucleotide excision repair pathway, removing platinum-induced DNA adducts and contributing to cisplatin resistance. Detecting ERCC1 overexpression is important in considering treatment options for metastatic TNBC, including individualized approaches to therapy, and may facilitate improved responses or reduction of unnecessary toxicity. We hypothesized that assigning cisplatin based on pretreatment ERCC1 expression would improve response and survival. This study was conducted to assess the impact of ERCC1 expression on PFS, OS and response rates in metastatic triple negative breast cancer patients treated with platinum-based chemotherapy. Methods: From June 2012 to November 2013, 52 metastatic triple negative breast cancer patients were enrolled. ERCC1 protein expression was detected from pretreatment biopsies by Immunohistochemistry. All patients received cisplatin plus paclitaxel. The primary end point was the impact of ERCC1 expression on PFS and OS. Results: 34 patients (65.4%) showed positive ERCC1 expression while 18 (34.6%) proved negative. Positive ERCC1 expression was associated with short PFS (median, 5 months vs. 7 months; P = 0.043), short OS (median, 9 months vs. 11 months; P = 0.033) and poor response to cisplatin based chemotherapy (P = 0.046). Conclusions: This prospective study further validated ERCC1 as a reliable biomarker for customized chemotherapy in metastatic triple negative breast cancer patients. High expression of ERCC1 was thereby fond to be significantly associated with poor outcome in patients treated with platinum based chemotherapy. Creative Commons Attribution License

  2. [Taxane-cisplatin-fluorouracil as induction chemotherapy for advanced head and neck cancer: a Meta-analysis of the efficacy and safety].

    PubMed

    Jian, Jiejun; Li, Guoyi; Yu, Zizhong; Tian, Lei

    2016-02-01

    To systematically review the efficacy and safety of taxane, cisplatin, and fluorouracil (Tax-PF) as induction chemotherapy for advanced head and neck cancer. Literature about the efficacy and safety of Taxane-cisplatin-fluorouracil as induction chemotherapy for advanced head and neck cancer was retrieved from digital databases of PubMed, Embase, SpringerLink, MEDLINE and the Cochrane Library before February 2015. Data extraction and quality assessment of included studies were conducted by two reviewers independently. Stata 13.0 was then used to perform Meta-analysis. A total 7 randomized controlled trials involving 2,702 were included. The 3-year OS rate [HR = 1.14, 95% CI (1.03, 1.25), P < 0.01], 3-year PFS rate [HR = 1.24, 95% CI (1.08, 1.43), P < 0.01], 5-year OS rate [HR = 1.30, 95% CI (1.09, 1. 55), P < 0. 01], 5-year PFS rate [HR = 1.39, 95% CI (1.14, 1.70), P < 0.01] and ORR to chemotherapy [OR = 1.66, 95% CI (1.35, 2.05), P < 0.01] of the patients in the Tax-PF group were statistically superior to those in the PF group. In terms of toxicities, the incidence of febrile neutropenia [OR = 2.36, 95% CI (1.62, 3.46), P < 0.01], alopecia [OR = 8.22, 95% CI (3.99, 16.92), P < 0.01], diarrhea [OR = 1.57, 95% CI (1.05, 2.36), P< 0.05] and leucopenia [OR = 2.79, 95% CI (1.86, 4.21), P < 0.01] was higher in the Tax-PF group than that in the PF group. The Tax-PF induction chemotherapy improved PFS and OS, and the ORR was better as compared to PF-based therapy regimens at the cost of a higher incidence of adverse events.

  3. Comparison of Four Cisplatin-Based Radiochemotherapy Regimens for Nonmetastatic Stage III/IV Squamous Cell Carcinoma of the Head and Neck;Head-and-neck cancer; Cisplatin-based radiochemotherapy; Toxicity; Treatment outcomes

    SciTech Connect

    Rades, Dirk; Kronemann, Stefanie; Meyners, Thekla; Bohlen, Guenther; Tribius, Silke; Kazic, Nadja; Schroeder, Ursula; Hakim, Samer G.; Schild, Steven E.; Dunst, Juergen

    2011-07-15

    Purpose: To compare the outcomes of four cisplatin-based radiochemotherapy regimens in 311 patients with Stage III/IV squamous cell carcinoma of the head and neck. Methods and Materials: Concurrent chemotherapy consisted of three courses of cisplatin 100 mg/m{sup 2} on Day 1 (Group A, n = 74), two courses of cisplatin 20 mg/m{sup 2} on Days 1-5 plus 5-fluorouracil 1,000 mg/m{sup 2} on Days 1-5 (Group B, n = 49), two courses of cisplatin 20 mg/m{sup 2} on Days 1-5 plus 5-fluorouracil 600 mg/m{sup 2} on Days 1-5 (Group C, n = 102), or two courses of cisplatin 20 mg/m{sup 2} on Days 1-5 (Group D, n = 86). The groups were retrospectively compared for toxicity and outcomes, and 11 additional factors were evaluated for outcomes. Results: No significant difference was observed among the groups regarding radiation-related acute oral mucositis and radiation-related late toxicities. Acute Grade 3 skin toxicity was significantly more frequent in Group B than in the patients of the other three groups (p = .013). The chemotherapy-related Grade 3 nausea/vomiting rate was 24% for Group A, 8% for Group B, 9% for Group C, and 6% for Group D (p = .003). The corresponding Grade 3 nephrotoxicity rates were 8%, 1%, 2%, and 1% (p = .019). The corresponding Grade 3-4 hematologic toxicity rates were 35%, 41%, 19%, and 21% (p = .027). Chemotherapy could be completed in 50%, 59%, 74%, and 83% of the Group A, B, C, and D patients, respectively (p = .002). Toxicity-related radiotherapy breaks occurred in 39%, 43%, 21%, and 15% of Groups A, B, C, and D, respectively (p = .005). The 3-year locoregional control rate was 67%, 72%, 60%, and 59% for Groups A, B, C, and D, respectively (p = .48). The corresponding 3-year metastasis-free survival rates were 67%, 74%, 63%, and 79% (p = .31), and the corresponding 3-year survival rates were 60%, 63%, 50%, and 71% (p = .056). On multivariate analysis, Karnofsky performance status, histologic grade, T/N category, preradiotherapy hemoglobin level

  4. [Trial of home anti-cancer chemotherapy with infusion of 5-FU and low-dose cisplatin].

    PubMed

    Muto, A; Ashino, Y; Ito, H; Kanno, A; Moriyama, A; Hiraga, M

    1996-12-01

    We tried home anti-cancer chemotherapy for patients with advanced or recurrent cancer of the digestive system, using two disposable balloon pumps connected to an implantable drug delivery system via central venous line. There were 33 patients under 75 years old, including 20 cases of gastric cancer, 9 cases of colorectal cancer, 2 cases of cholangiocarcinoma and 2 cases of esophageal cancer enrolled in this study. The protocol was combined chemotherapy with continuous intravenous infusion of 5-FU (300 mg/body/day) and low-dose intravenous injection of cisplatin (5 mg/body/day) in 10-day courses for two weeks, and it was repeated 3 times for 6 weeks. Because of side effects such as nausea, vomiting and bone marrow suppression, treatment was discontinued in 12 cases with peritoneal cancer infiltration. In two of 10 with estimable disease, the reduction of the metastatic lymph node was observed, but no effect was shown in the colorectal metastatic liver tumor. Thanks to the portability of the pump with this method, the patient need not undergo hospitalization. Moreover, there is no renal dysfunction or other major side effects, quality of life is not compromised and a return to family and social life is possible. Thus, if the patient cannot take the oral nutrition, it is easy to start home hyper-alimentation.

  5. Role of the DNA Base Excision Repair Protein, APE1 in Cisplatin, Oxaliplatin, or Carboplatin Induced Sensory Neuropathy

    PubMed Central

    Kelley, Mark R.; Jiang, Yanlin; Guo, Chunlu; Reed, April; Meng, Hongdi; Vasko, Michael R.

    2014-01-01

    Although chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect of platinum drugs, the mechanisms of this toxicity remain unknown. Previous work in our laboratory suggests that cisplatin-induced CIPN is secondary to DNA damage which is susceptible to base excision repair (BER). To further examine this hypothesis, we studied the effects of cisplatin, oxaliplatin, and carboplatin on cell survival, DNA damage, ROS production, and functional endpoints in rat sensory neurons in culture in the absence or presence of reduced expression of the BER protein AP endonuclease/redox factor-1 (APE1). Using an in situ model of peptidergic sensory neuron function, we examined the effects of the platinum drugs on hind limb capsaicin-evoked vasodilatation. Exposing sensory neurons in culture to the three platinum drugs caused a concentration-dependent increase in apoptosis and cell death, although the concentrations of carboplatin were 10 fold higher than cisplatin. As previously observed with cisplatin, oxaliplatin and carboplatin also increased DNA damage as indicated by an increase in phospho-H2AX and reduced the capsaicin-evoked release of CGRP from neuronal cultures. Both cisplatin and oxaliplatin increased the production of ROS as well as 8-oxoguanine DNA adduct levels, whereas carboplatin did not. Reducing levels of APE1 in neuronal cultures augmented the cisplatin and oxaliplatin induced toxicity, but did not alter the effects of carboplatin. Using an in vivo model, systemic injection of cisplatin (3 mg/kg), oxaliplatin (3 mg/kg), or carboplatin (30 mg/kg) once a week for three weeks caused a decrease in capsaicin-evoked vasodilatation, which was delayed in onset. The effects of cisplatin on capsaicin-evoked vasodilatation were attenuated by chronic administration of E3330, a redox inhibitor of APE1 that serendipitously enhances APE1 DNA repair activity in sensory neurons. These outcomes support the importance of the BER pathway, and particularly APE

  6. Sensitization of cisplatin therapy by a naphthalimide based organoselenium compound through modulation of antioxidant enzymes and p53 mediated apoptosis.

    PubMed

    Ghosh, P; Singha Roy, S; Basu, A; Bhattacharjee, A; Bhattacharya, S

    2015-04-01

    The widely used anti-cancer drug cisplatin imparts various toxic manifestations in the host, with nephrotoxicity being the most severe one. The trace element selenium shows antioxidant activity in both human and animals. The present study was designed to assess the chemoprotecting and chemoenhancing efficacy of a naphthalimide based organoselenium compound 2-(5-selenocyanato-pentyl)-benzo[de]isoquinoline 1,3-dione during cisplatin chemotherapy in mice bearing Ehrlich ascites carcinoma cells. Cisplatin (5 mg/kg b.w.) was administered intraperitoneally and the organoselenium compound (3 mg/kg b.w.) was given by oral gavage in concomitant and pretreatment schedule. The effects of the test compound was evaluated by assaying biochemical, hematological, histological, genotoxicity parameters and by investigating induction of apoptosis in tumor cells, and calculating tumor growth response in the host. The organoselenium compound significantly prevented cisplatin induced generation of reactive oxygen species (ROS), reactive nitrogen species, and onset of lipid peroxidation in the kidney tissue of the experimental mice. In addition, the test compound was also substantially restored cisplatin induced depleted activities of the renal antioxidant enzymes and reduced glutathione level; prevented the serum blood urea nitrogen level, creatinine level, chromosomal aberration, DNA damage, histological alterations of kidney, and normalized the hematological profile of the tumor bearing mice. Furthermore, the organoselenium compound alone or during combination therapy induced apoptosis in tumor cells through mitochondria mediated and DNA damage mediated pathway and ultimately increased the life span of the tumor bearing host. Hence, the results showed that the test compound not only reduced the toxicity of cisplatin but also enhanced its anti-tumor efficacy.

  7. Gemcitabine, dexamethasone, and cisplatin (GDP) as salvage chemotherapy for patients with relapsed or refractory peripheral T cell lymphoma-not otherwise specified.

    PubMed

    Qi, Fei; Dong, Mei; He, Xiaohui; Li, Yexiong; Wang, Weihu; Liu, Peng; Yang, Jianliang; Gui, Lin; Zhang, Changgong; Yang, Sheng; Zhou, Shengyu; Shi, Yuankai

    2017-02-01

    Standard therapeutic options for patients with relapsed or refractory peripheral T cell lymphoma-not otherwise specified (PTCL-NOS) remain unclear. There are few large cohort studies specifically focused on gemcitabine-based chemotherapy for PTCL-NOS. We retrospectively reviewed patients with relapsed or refractory PTCL-NOS who received salvage GDP (gemcitabine, dexamethasone, and cisplatin) chemotherapy at the Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China, from May 2008 to August 2014. Twenty-five patients were enrolled and analyzed. The median number of cycles of GDP chemotherapy per patient was four (range, 2-8 cycles). Overall response rate was 64.0% (16/25) with five achieved complete remission or complete remission unconfirmed. After a median follow-up of 9 months, median overall survival (OS) and progression-free survival after relapse or progression (second-PFS) were 9.3 and 5.4 months. One-year PFS rate and 1-year OS rate were 27.4% and 43.9%, respectively. Median second-PFS was significantly longer in patients sensitive to GDP than the ones resistant to the treatment (10.3 vs. 2.8 months, p < .01). In addition, the low International Prognostic Index, low Prognostic Index for T cell lymphoma, or normal level of LDH in serum was associated with favorable prognosis. Grade 3/4 adverse effect was observed in 10 of 25 patients treated with GDP including neutropenia (8/25), thrombocytopenia (5/25), and anemia (4/25). Taken together, our study suggests that GDP is an effective and optional salvage regimen for relapsed or refractory PTCL-NOS.

  8. [Second-line chemotherapy with gemcitabine and cisplatin for urothelial cancer previously treated with or resistant to M-VAC therapy].

    PubMed

    Honda, Masahito; Hatano, Koji; Satoh, Mototaka; Tsujimoto, Yuichi; Takada, Tsuyoshi; Matsumiya, Kiyomi; Fujioka, Hideki

    2006-09-01

    We evaluated the efficacy of gemcitabine-cisplatin (GC) therapy as a second line chemotherapy for recurrent urothelial cancer previously treated with or resistant to methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) therapy. Four patients who had recurrent cancer after adjuvant M-VAC therapy and five patients with resistant lesions to M-VAC were treated by GC. Of the nine patients, three completely responded to GC and three obtained partial response. These complete responders were cancer-free for 34, 32 and 24 months. In one partial responder, the metastatic masses have been decreasing in size for 12 months after completion of GC therapy. Our findings suggested that GC would be useful as a second line chemotherapy for urothelial cancer previously treated with M-VAC.

  9. Treatment of isolated mediastinal and hilar recurrence of lung cancer with bronchoscopic endobronchial ultrasound guided intratumoral injection of chemotherapy with cisplatin.

    PubMed

    Mehta, Hiren J; Begnaud, Abbie; Penley, Andrea M; Wynne, John; Malhotra, Paras; Fernandez-Bussy, Sebastian; Cope, Jessica M; Shuster, Jonathan J; Jantz, Michael A

    2015-12-01

    A common pattern of recurrence in lung cancer after receiving full dose external beam radiation therapy (EBRT) to targeted sites is isolated mediastinal and hilar recurrence (IMHR). Treatment options for these patients are limited to palliative radiation, chemotherapy, and/or best supportive care. We describe our experience with treating IMHR with bronchoscopic endobronchial ultrasound (EBUS) guided intratumoral injection of cisplatin (ITC). Patients treated between Jan 2009-September 2014 with ITC for IMHR were included. Patient demographics, tumor histology, size, concurrent therapy, location, number of sites treated, treatment sessions, and encounters were abstracted. Responses were analyzed on follow-up scans 8-12 weeks after the last treatment session using RECIST 1.1 criteria. Locoregional recurrence, progression-free survival (PFS), and overall survival were measured. 50 sites were treated in 36 patients (19 males, 17 females) with mean age 61.9±8.5 years. Eight sites treated on subsequent encounters were excluded and one patient had an unevaluable response, leaving 35 patients and 41 sites for final analysis. 24/35 (69%) had complete or partial response (responders), whereas 11/35 (31%) had stable or progressive disease (non-responders). There were no significant differences in response based on histology, size, and concurrent therapy. Median survival for the group was 8 months (95% CI of 6-11 mo). Responders had significantly higher survival and PFS than non-responders. Two patients treated with concurrent EBRT, developed broncho-mediastinal fistula. EBUS guided intratumoral cisplatin for IMHR appears to be safe and effective, and may represent a new treatment paradigm for this patient population. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. Concomitant chemobrachyradiotherapy with ifosfamide and cisplatin followed by consolidation chemotherapy in locally advanced squamous cell carcinoma of the uterine cervix: Results of a phase II study

    SciTech Connect

    Vrdoljak, Eduard . E-mail: eduard.vrdoljak@st.hinet.hr; Prskalo, Tomislav; Omrcen, Tomislav; Situm, Kristina; Boraska, Tihana; Frleta Ilic, Nives; Jankovic, Stjepan; Hamm, Wolfgang

    2005-03-01

    Purpose: To evaluate the efficacy and toxicity of ifosfamide and cisplatin administered concomitantly with low-dose-rate brachytherapy followed by consolidation chemotherapy in the treatment of locally advanced squamous cell cervical carcinoma (LASCC). Methods and materials: Forty-four patients with biopsy-proven LASCC were enrolled. FIGO Stages IB2 bulky to IVA were entered into this study. Patients were assigned to receive external radiotherapy (50 Gy in 25 fractions); then ifosfamide 2 g/m{sup 2} plus cisplatin 75 mg/m{sup 2} was applied during two low-dose-rate brachytherapy applications, and 4 cycles of consolidation chemotherapy with the same drug combination were given after completion of radiotherapy. The planned dose to point A was 85 Gy. Results: All patients received both courses of concomitant chemobrachytherapy and at least 1 cycle of consolidation chemotherapy. The average duration of radiation was 45.1 days. The clinical complete response rate was 100%. Grade 3 and 4 leukopenia occurred in 25% and 11% of the cycles, respectively. After a median follow-up of 34 months (range, 20-54 months), the recurrence-free and the overall survival rates were 84% and 91%, respectively. Major delayed local complications occurred in 7 cases (16%). Conclusions: These results indicate that concomitant chemobrachyradiotherapy with ifosfamide and cisplatin is a feasible combination for patients with LASCC of the cervix uteri. A randomized trial is planned.

  11. [A case of advanced esophagogastric junction cancer responding to pre-operative combination chemotherapy of docetaxel, cisplatin, S-1, and trastuzumab].

    PubMed

    Haruki, Shigeo; Takiguchi, Noriaki; Arita, Kaida; Usui, Shinsuke; Ito, Koji; Matsumoto, Akiyo; Hiranuma, Susumu; Bhunachet, Ekapot

    2013-08-01

    We have no consensus on surgical treatment and chemotherapy for esophagogastric junction cancer in Japan. A 51-yearold man reporting dysphagia was examined, and through upper gastrointestinal endoscopy was found to have a tumor at the esophagogastric junction. Histologically, biopsy specimens indicated adenocarcinoma with genetic amplification of human epidermal growth factor receptor type 2(HER2). Positron emission tomography showed swelling of several abdominal lymph nodes with accumulation of fluorodeoxyglucose. He was treated with esophagogastorectomy with left thoracotomy after combination chemotherapy of docetaxel, cisplatin, S-1, and trastuzumab. He had no complication from the operation and had no adverse effect from the combination chemotherapy. Histopathological examination of the resected specimen showed a minute residual cancer nest at the muscularis propria of the esophagus, but no lymph node metastasis. This regimen could be useful for advanced junctional cancer with HER2 amplification as preoperative chemotherapy.

  12. Cisplatin resistance and opportunities for precision medicine.

    PubMed

    Amable, Lauren

    2016-04-01

    Cisplatin is one of the most commonly used chemotherapy drugs, treating a wide range of cancer types. Unfortunately, many cancers initially respond to platinum treatment but when the tumor returns, drug resistance frequently occurs. Resistance to cisplatin is attributed to three molecular mechanisms: increased DNA repair, altered cellular accumulation, and increased drug inactivation. The use of precision medicine to make informed decisions on a patient's cisplatin resistance status and predicting the tumor response would allow the clinician to tailor the chemotherapy program based on the biology of the disease. In this review, key biomarkers of each molecular mechanism will be discussed along with the current clinical research. Additionally, known polymorphisms for each biomarker will be discussed in relation to their influence on cisplatin resistance.

  13. Responses and adverse effects of carboplatin-based chemotherapy for pediatric intracranial germ cell tumors.

    PubMed

    Ji, Suntae; Chueh, Hee Won; Kim, Ju Youn; Lim, Su Jin; Cho, Eun Joo; Lee, Soo Hyun; Yoo, Keon Hee; Sung, Ki Woong; Koo, Hong Hoe

    2011-03-01

    Cisplatin-based chemotherapy has been commonly used for the treatment of intracranial germ cell tumors (IC-GCTs). However, this treatment exhibits some adverse effects such as renal problems and hearing difficulty. Carboplatin-based chemotherapy was administered to pediatric patients with IC-GCTs from August 2004 at the Samsung Medical Center. In this study, we assessed the responses and adverse effects of carboplatin-based chemotherapy in pediatric IC-GCTs patients according to the risk group, and compared the results with those of the previous cisplatin-based chemotherapy. We examined 35 patients (27 men and 8 women) diagnosed with IC-GCTs between August 2004 and April 2008 and received risk-adapted carboplatin-based chemotherapy at the Samsung Medical Center. Patients were divided into either low-risk (LR) or high-risk (HR) groups and a retrospective analysis was performed using information from the medical records. Although hematological complications were common, hearing difficulties or grade 3 or 4 creatinine level elevation were not observed in patients who underwent carboplatin-based chemotherapy. The frequency of febrile neutropenia did not differ between the risk groups. The overall survival was 100% and event-free survival (EFS) was 95.7%. The EFS rate was 100% in the LR group and 90% in the HR group, respectively. Despite their common occurrence in high-risk patients, no lethal hematological complications were associated with carboplatin-based treatment. The current carboplatin-based chemotherapy protocol is safe and effective for the treatment of pediatric patients with IC-GCTs.

  14. A randomized study of chemotherapy with cisplatin plus etoposide versus chemoendocrine therapy with cisplatin, etoposide and the pineal hormone melatonin as a first-line treatment of advanced non-small cell lung cancer patients in a poor clinical state.

    PubMed

    Lissoni, P; Paolorossi, F; Ardizzoia, A; Barni, S; Chilelli, M; Mancuso, M; Tancini, G; Conti, A; Maestroni, G J

    1997-08-01

    Recent studies suggest that the pineal hormone melatonin may reduce chemotherapy-induced immune and bone marrow damage. In addition, melatonin may exert potential oncostatic effects either by stimulating host anticancer immune defenses or by inhibiting tumor growth factor production. On this basis, we have performed a randomized study of chemotherapy alone vs. chemotherapy plus melatonin in advanced non-small cell lung cancer patients (NSCLC) with poor clinical status. The study included 70 consecutive advanced NSCLC patients who were randomized to receive chemotherapy alone with cisplatin (20 mg/m2/day i.v. for 3 days) and etoposide (100 mg/m2/day i.v. for 3 days) or chemotherapy plus melatonin (20 mg/day orally in the evening). Cycles were repeated at 21-day intervals. Clinical response and toxicity were evaluated according to World Health Organization criteria. A complete response (CR) was achieved in 1/34 patients concomitantly treated with melatonin and in none of the patients receiving chemotherapy alone. Partial response (PR) occurred in 10/34 and in 6/36 patients treated with or without melatonin, respectively. Thus, the tumor response rate was higher in patients receiving melatonin (11/34 vs. 6/35), without, however, statistically significant differences. The percent of 1-year survival was significantly higher in patients treated with melatonin plus chemotherapy than in those who received chemotherapy alone (15/34 vs. 7/36, P < 0.05). Finally, chemotherapy was well tolerated in patients receiving melatonin, and in particular the frequency of myelosuppression, neuropathy, and cachexia was significantly lower in the melatonin group. This study shows that the concomitant administration of melatonin may improve the efficacy of chemotherapy, mainly in terms of survival time, and reduce chemotherapeutic toxicity in advanced NSCLC, at least in patients in poor clinical condition.

  15. Phase II study of docetaxel, cisplatin and capecitabine as preoperative chemotherapy in resectable gastric cancer.

    PubMed

    Dassen, Anneriet E; Bernards, Nienke; Lemmens, Valery E P P; van de Wouw, Yes A J; Bosscha, Koop; Creemers, Geert-Jan; Pruijt, Hans J F M

    2016-10-27

    To investigate the feasibility of preoperative docetaxel, cisplatin and capecitabine (DCC) in patients with resectable gastric cancer. Patients with resectable gastric cancer fulfilling the inclusion criteria, were treated with 4 cycles of docetaxel (60 mg/m(2)), cisplatin (60 mg/m(2)) and capecitabine (1.875 mg/m(2) orally on day 1-14, two daily doses) repeated every three weeks, followed by surgery. Primary end point was the feasibility and toxicity/safety profile of DCC, secondary endpoints were pathological complete resection rate and pathological complete response (pCR) rate. All of the patients (51) were assessable for the feasibility and safety of the regimen. The entire preoperative regimen was completed by 68.6% of the patients. Grade III/IV febrile neutropenia occurred in 10% of all courses. Three patients died due to treatment related toxicity (5.9%), one of them (also) because of refusing further treatment for toxicity. Of the 45 patients who were evaluable for secondary endpoints, four developed metastatic disease and 76.5% received a curative resection. In 3 patients a pCR was seen (5.9%), two patients underwent a R1 resection (3.9%). Four courses of DCC as a preoperative regimen for patients with primarily resectable gastric cancer is highly demanding. The high occurrence of febrile neutropenia is of concern. To decrease the occurrence of febrile neutropenia the prophylactic use of granulocyte colony-stimulating factor (G-CSF) should be explored. A curative resection rate of 76.5% is acceptable. The use of DCC without G-CSF support as preoperative regimen in resectable gastric cancer is debatable.

  16. Phase II study of docetaxel, cisplatin and capecitabine as preoperative chemotherapy in resectable gastric cancer

    PubMed Central

    Dassen, Anneriet E; Bernards, Nienke; Lemmens, Valery E P P; van de Wouw, Yes A J; Bosscha, Koop; Creemers, Geert-Jan; Pruijt, Hans J F M

    2016-01-01

    AIM To investigate the feasibility of preoperative docetaxel, cisplatin and capecitabine (DCC) in patients with resectable gastric cancer. METHODS Patients with resectable gastric cancer fulfilling the inclusion criteria, were treated with 4 cycles of docetaxel (60 mg/m2), cisplatin (60 mg/m2) and capecitabine (1.875 mg/m2 orally on day 1-14, two daily doses) repeated every three weeks, followed by surgery. Primary end point was the feasibility and toxicity/safety profile of DCC, secondary endpoints were pathological complete resection rate and pathological complete response (pCR) rate. RESULTS All of the patients (51) were assessable for the feasibility and safety of the regimen. The entire preoperative regimen was completed by 68.6% of the patients. Grade III/IV febrile neutropenia occurred in 10% of all courses. Three patients died due to treatment related toxicity (5.9%), one of them (also) because of refusing further treatment for toxicity. Of the 45 patients who were evaluable for secondary endpoints, four developed metastatic disease and 76.5% received a curative resection. In 3 patients a pCR was seen (5.9%), two patients underwent a R1 resection (3.9%). CONCLUSION Four courses of DCC as a preoperative regimen for patients with primarily resectable gastric cancer is highly demanding. The high occurrence of febrile neutropenia is of concern. To decrease the occurrence of febrile neutropenia the prophylactic use of granulocyte colony-stimulating factor (G-CSF) should be explored. A curative resection rate of 76.5% is acceptable. The use of DCC without G-CSF support as preoperative regimen in resectable gastric cancer is debatable. PMID:27830043

  17. Assessing the effectiveness and safety of liposomal paclitaxel in combination with cisplatin as first-line chemotherapy for patients with advanced NSCLC with regional lymph-node metastasis: study protocol for a randomized controlled trial (PLC-GC trial).

    PubMed

    Hu, Luo; Liang, Gong; Yuliang, Wang; Bingjing, Zhu; Xiangdong, Zhou; Rufu, Xu

    2013-02-15

    Lung cancer is still the leading cause of cancer-related mortality worldwide. Around 80 to 85% of lung cancers are non-small cell lung cancer (NSCLC). Regional lymphatic metastasis is a frequent occurrence in NSCLC, and the extent of lymphatic dissemination significantly determines the prognosis of patients with NSCLC. Hence, identification of alternative treatments for these patients should be considered a priority. Liposomal paclitaxel is a new formulation composed of paclitaxel and liposomes, with favorable pharmacokinetic properties. In particular, it produces dramatically higher drug concentrations in the lymph nodes than occurs with the current formulations of paclitaxel, thus we believe that patients with NSCLC with regional lymphatic metastasis may benefit from this new drug. Cisplatin-based doublet chemotherapy is recommended as the first-line treatment for patients with advanced NSCLC. We have designed a trial to assess whether first-line chemotherapy using liposomal paclitaxel combined with cisplatin (LP regimen) is superior to gemcitabine combined with cisplatin (GP regimen) in efficacy (both short-term and long-term efficacy) and safety (adverse events; AEs). This is a prospective, open-label, controlled randomized clinical trial (RCT) to assess the therapeutic effects and safety of liposomal paclitaxel. The study aims to enroll 126 patients, who will be randomly allocated to one of the two treatment groups (LP and GP), with 63 patients in each group. Patients will receive four to six cycles of the assigned chemotherapy, and primary outcome will be assessed every two cycles. Patients will be recommended for surgery if the tumor becomes resectable. All participants will be followed up for at least 12 months. The objective response rate (ORR), changes in regional lymphatic metastasis (including number and size) and TNM (tumor, node, metastasis) staging will be the primary outcome measures. Progression-free survival, objective survival, median survival

  18. A Phase II Study of Bevacizumab in Combination With Definitive Radiotherapy and Cisplatin Chemotherapy in Untreated Patients With Locally Advanced Cervical Carcinoma: Preliminary Results of RTOG 0417

    SciTech Connect

    Schefter, Tracey E.; Winter, Kathryn; Kwon, Janice S.; Stuhr, Kelly; Balaraj, Khalid; Yaremko, Brian P.; Small, William; Gaffney, David K.

    2012-07-15

    Purpose: Concurrent cisplatin-based chemoradiotherapy (CRT) is the standard treatment for locally advanced cervical cancer. RTOG 0417 was a Phase II study exploring the safety and efficacy of the addition of bevacizumab to standard CRT. Methods and Materials: Eligible patients with bulky tumors (Stage IB-IIIB) were treated with once-weekly cisplatin (40 mg/m{sup 2}) chemotherapy and standard pelvic radiotherapy and brachytherapy. Bevacizumab was administered at 10 mg/kg intravenously every 2 weeks for three cycles. Treatment-related serious adverse event (SAE) and other adverse event (AE) rates within the first 90 days from treatment start were determined. Treatment-related SAEs were defined as any Grade {>=}4 vaginal bleeding or thrombotic event or Grade {>=}3 arterial event, gastrointestinal (GI) bleeding, or bowel/bladder perforation, or any Grade 5 treatment-related death. Treatment-related AEs included all SAEs and Grade 3 or 4 GI toxicity persisting for >2 weeks despite medical intervention, Grade 4 neutropenia or leukopenia persisting for >7 days, febrile neutropenia, Grade 3 or 4 other hematologic toxicity, and Grade 3 or 4 GI, renal, cardiac, pulmonary, hepatic, or neurologic AEs. All AEs were scored using the National Cancer Institute Common Terminology Criteria (CTCAE) v 3.0 (MedDRA version 6.0). Results: A total of 60 patients from 28 institutions were enrolled between 2006 and 2009, and of these, 49 patients were evaluable. The median follow-up was 12.4 months (range, 4.6-31.4 months).The median age was 45 years (range, 22-80 years). Most patients had FIGO Stage IIB (63%) and were of Zubrod performance status of 0 (67%). 80% of cases were squamous. There were no treatment-related SAEs. There were 15 (31%) protocol-specified treatment-related AEs within 90 days of treatment start; the most common were hematologic (12/15; 80%). 18 (37%) occurred during treatment or follow-up at any time. 37 of the 49 patients (76%) had cisplatin and bevacizumab

  19. Chemotherapy

    MedlinePlus

    ... the cancer cells. This is called palliative chemotherapy. Chemotherapy for conditions other than cancer Some chemotherapy drugs ... you'll receive. Side effects that occur during chemotherapy treatment Common side effects of chemotherapy drugs include: ...

  20. Developing a Highly Stable PLGA-mPEG Nanoparticle Loaded with Cisplatin for Chemotherapy of Ovarian Cancer

    PubMed Central

    Cheng, Lihua; Jin, Chengmeng; Lv, Wen; Ding, Qiuping; Han, Xu

    2011-01-01

    Background Cisplatin is a potent anticancer drug, but its clinical application has been limited due to its undesirable physicochemical characteristics and severe side effects. Better drug formulations for cisplatin are highly desired. Methodology/Principal Findings Herein, we have developed a nanoparticle formulation for cisplatin with high encapsulation efficiency and reduced toxicity by using cisplatin-crosslinked carboxymethyl cellulose (CMC) core nanoparticles made from poly(lactide-co-glycolide)-monomethoxy-poly(polyethylene glycol) copolymers (PLGA-mPEG). The nanoparticles have an average diameter of approximately 80 nm measured by transmission electron microscope (TEM). The encapsulation efficiency of cisplatin in the nanoparticles is up to 72%. Meanwhile, we have also observed a controlled release of cisplatin in a sustained manner and dose-dependent treatment efficacy of cisplatin-loaded nanoparticles against IGROV1-CP cells. Moreover, the median lethal dose (LD50) of the cisplatin-loaded nanoparticles was more than 100 mg/kg by intravenous administration, which was much higher than that of free cisplatin. Conclusion This developed cisplatin-loaded nanoparticle is a promising formulation for the delivery of cisplatin, which will be an effective therapeutic regimen of ovarian cancer without severe side effects and cumulative toxicity. PMID:21966528

  1. Duration of cisplatin excretion in breast milk.

    PubMed

    Hays, Karen E; Ryu, Rachel J; Swisher, Elizabeth M; Reed, Eddie; McManus, Terry; Rybeck, Blanche; Petros, William P; Hebert, Mary F

    2013-11-01

    Cisplatin, a platinum-based chemotherapy agent, is commonly used in treating cancers that may affect women of childbearing age, including cervical cancer, triple-negative breast cancer, and pediatric tumors in adolescents. The authors found that platinum was undetectable in breast milk at 66 hours and beyond following a 70-mg dose of intravenous cisplatin. Relative infant dose of platinum was calculated to be between 0.29% and 0.40% of the maternal dose corrected for body weight. This case demonstrates minimal exposure to platinum via breast milk, following a single 70-mg intravenous dose of cisplatin.

  2. Results of third-generation epirubicin/cisplatin/xeloda adjuvant chemotherapy in patients with radically resected gastric cancer.

    PubMed

    Cainap, Calin; Nagy, Viorica; Seicean, Andrada; Gherman, Alexandra; Laszlo, Istvan; Lisencu, Cosmin; Nadim, Al Hajar; Constantin, Anne-Marie; Cainap, Simona

    2016-01-01

    The purpose of this study was to evaluate the efficacy and toxicity of a third-generation chemotherapy regimen in the adjuvant setting to radically operated patients with gastric cancer. This proposed new adjuvant regimen was also compared with a consecutive retrospective cohort of patients treated with the classic McDonald regimen. Starting in 2006, a non-randomized prospective phase II study was conducted at the Institute of Oncology of Cluj-Napoca on 40 patients with stage IB-IV radically resected gastric adenocarcinoma. These patients were administered a chemotherapy regimen already considered to be standard treatment in the metastatic setting: ECX (epirubicin, cisplatin, xeloda) and were compared to a retrospective control group consisting of 54 patients, treated between 2001 and 2006 according to McDonald's trial. In a previous paper, we reported toxicities and the possible predictive factors for these toxicities; in the present article, we report on the results concerning predictive factors on overall survival (OS) and disease free survival (DFS). The proposed ECX treatment was not less effective than the standard suggested by McDonald's trial. Age was an independent prognostic factor in multivariate analysis. N3 stage was an independent prognostic factor for OS and DFS. N ratio >70% was an independent predictive factor for OS and locoregional disease control. The resection margins were independent prognostic factors for OS and DFS. The proposed treatment is not less effective compared with the McDonald's trial. Age was an independent prognostic factor in multivariate analysis. N3 stage represented an independent prognostic factor and N ratio >70% was a predictive factor for OS and DFS. The resection margins were proven to be independent prognostic factors for OS and DFS.

  3. Intra-Arterial Infusion Chemotherapy Using Cisplatin With Radiotherapy for Stage III Squamous Cell Carcinoma of the Cervix

    SciTech Connect

    Kaneyasu, Yuko Nagai, Nobutaka; Nagata, Yasushi; Hashimoto, Yasutoshi; Yuki, Shintaro; Murakami, Yuji; Kenjo, Masahiro; Kakizawa, Hideaki; Toyota, Naoyuki; Fujiwara, Hisaya; Kudo, Yoshiki; Ito, Katsuhide

    2009-10-01

    Purpose: To examine the effectiveness of concomitant intra-arterial infusion chemotherapy (IAIC) using cisplatin (CDDP) with radiotherapy for Stage III squamous cell carcinoma of the cervix. Materials and Methods: We analyzed 29 cases of Stage III squamous cell carcinoma of the uterine cervix treated with radiotherapy and IAIC of CDDP from 1991 to 2006. External-beam therapy was given to the whole pelvis using four opposing parallel fields with an 18-MV linear accelerator unit. A central shield was used after 30-40 Gy with external whole-pelvic irradiation, and the total dose was 50 Gy. High-dose-rate brachytherapy was given with {sup 192}Ir microSelectron. The dose at Point A was 6 Gy per fraction, 2 fractions per week, and the total number of fractions was either 3 or 4. Two or three courses of IAIC were given concomitantly with CDDP 120 mg or carboplatin 300 mg. Results: We confirmed excellent medicine distribution directly by using computed tomographic angiography. The 5-year overall survival rate for Stage III patients was 62%, the cause-specific survival rate was 70%, and the local relapse-free survival rate was 89%. Local recurrence, distant metastasis, and occurrences of both were 7%, 38%, and 3%, respectively. The incidence of severe acute hematologic adverse reactions (Grade {>=}3) was 27% for all patients; however, all recovered without interruption of radiotherapy. Severe nonhematologic effects (Grade {>=}3) were 3%, including nausea and ileus. Only 1 patient's radiotherapy was interrupted for a period of 1 week because of ileus. Severe late complication rates (Grade {>=}3) for the bladder, rectum, and intestine were 3%, 3%, and 10%, respectively. Conclusion: A combination of IAIC and systemic chemotherapy should be considered to improve the prognosis of patients with Stage III squamous cell carcinoma of the cervix.

  4. Synergistic effects of cisplatin chemotherapy and gold nanorod-mediated hyperthermia on ovarian cancer cells and tumors

    PubMed Central

    Mehtala, Jonathan G; Torregrosa-Allen, Sandra; Elzey, Bennett D; Jeon, Mansik; Kim, Chulhong; Wei, Alexander

    2014-01-01

    Aim The synergistic effects of gold nanorod (GNR)-mediated mild hyperthermia (MHT; 42–43°C) and cisplatin (CP) activity was evaluated against chemoresistant SKOV3 cells in vitro and with a tumor xenograft model. Materials & methods In vitro studies were performed using CP at cytostatic concentrations (5 μM) and polyethylene glycol-stabilized GNRs, using near-infrared laser excitation for MHT. Results The amount of polyethylene glycol-GNRs used for environmental MHT was 1 μg/ml, several times lower than the loadings used in tumor tissue ablation. GNR-mediated MHT increased CP-mediated cytotoxicity by 80%, relative to the projected additive effect, and flow cytometry analysis suggested MHT also enhanced CP-induced apoptosis. In a pilot in vivo study, systemically administered polyethylene glycol-GNRs generated sufficient levels of MHT to enhance CP-induced reductions in tumor volume, despite their heterogeneous distribution in tumor tissue. Conclusion These studies imply that effective chemotherapies can be developed in combination with low loadings of nanoparticles for localized MHT. PMID:24498890

  5. Feasibility Study of Moderately Accelerated Intensity-Modulated Radiotherapy Plus Concurrent Weekly Cisplatin After Induction Chemotherapy in Locally Advanced Head-and Neck Cancer

    SciTech Connect

    Morganti, Alessio G.; Mignogna, Samantha; Deodato, Francesco; Massaccesi, Mariangela; Cilla, Savino; Calista, Franco; Serafini, Giovanni; Digesu, Cinzia; Macchia, Gabriella; Picardi, Vincenzo; Caravatta, Luciana; Di Lullo, Liberato; Giglio, Gianfranco; Sallustio, Giuseppina; Piermattei, Angelo

    2011-03-15

    Purpose: To evaluate the feasibility and efficacy of moderately accelerated intensity-modulated radiation therapy (IMRT) along with weekly cisplatin, after induction chemotherapy, in patients with locally advanced unresectable head and neck cancer (HNC). Methods and Materials: Patients with Stage III or IV locally advanced HNC, without progressive disease after three courses of induction chemotherapy, received concurrent chemo-IMRT (weekly cisplatin 30 mg/m{sup 2} plus simultaneous integrated boost IMRT). A total of 67.5 Gy in 30 fractions were delivered to primary tumor and involved nodes, 60 Gy in 30 fractions to high-risk nodal areas, and 55.5 Gy in 30 fractions to low-risk nodal areas. Results: In all, 36 patients (median age, 56 years) with International Union Against Cancer (UICC) Stage III (n = 5) and IV (n = 31) were included. Of the 36 patients, 17 had received CF (cisplatin and 5-fluorouracil (CF) and 19 had received docetaxel cisplatin and 5-fluorouracil (DCF). During concurrent chemoradiation, 11 of 36 patients (30.5%) experienced Grade III mucositis (CF, 47%; DCF, 15%; p < 0.04). Grade III pharyngeal-esophageal toxicity was observed in 5 of 19 patients (26.3%; CF, 0.0%; DCF, 26.3%; p = 0.02). Two patients died of complications (5.5%). After chemoradiation, the complete response rate was 63.8%. Two-year local control was 88.7%. Two-year progression free survival and overall survival were 74.5% and 60.9%, respectively. Conclusions: In our experience, a moderately accelerated chemo-IMRT was feasible after induction chemotherapy. However, a noteworthy early death rate of 5.5% was observed. Intensive supportive care strategies should be defined to better manage radiation-induced toxic effects. Longer follow-up is required to determine the incidence of late radiation toxicities and tumor control rates.

  6. Radiotherapy concurrently with weekly cisplatin, followed by adjuvant chemotherapy, for N2-3 nasopharyngeal cancer: a multicenter trial of the Forum for Nuclear Cooperation in Asia.

    PubMed

    Ohno, Tatsuya; Thinh, Dang Huy Quoc; Kato, Shingo; Devi, C R Beena; Tung, Ngo Thanh; Thephamongkhol, Kullathorn; Calaguas, Miriam Joy C; Zhou, Juying; Chansilpa, Yaowalak; Supriana, Nana; Erawati, Dyah; Banu, Parvin Akhter; Koo, Cho Chul; Kobayashi, Kunihiko; Nakano, Takashi; Tsujii, Hirohiko

    2013-05-01

    The purpose of this study was to evaluate the efficacy and toxicity of radiotherapy concurrently with weekly cisplatin, followed by adjuvant chemotherapy, for the treatment of N2-3 nasopharyngeal cancer (NPC) in Asian countries, especially regions of South and Southeast Asian countries where NPC is endemic. Between 2005 and 2009, 121 patients with NPC (T1-4 N2-3 M0) were registered from Vietnam, Malaysia, Indonesia, Thailand, The Philippines, China and Bangladesh. Patients were treated with 2D radiotherapy concurrently with weekly cisplatin (30 mg/m (2)), followed by adjuvant chemotherapy, consisting of cisplatin (80 mg/m(2) on Day 1) and fluorouracil (800 mg/m(2) on Days 1-5) for 3 cycles. Of the 121 patients, 56 patients (46%) required interruption of RT. The reasons for interruption of RT were acute non-hematological toxicities such as mucositis, pain and dermatitis in 35 patients, hematological toxicities in 11 patients, machine break-down in 3 patients, poor general condition in 2 patients, and others in 8 patients. Of the patients, 93% completed at least 4 cycles of weekly cisplatin during radiotherapy, and 82% completed at least 2 cycles of adjuvant chemotherapy. With a median follow-up time of 46 months for the surviving 77 patients, the 3-year locoregional control, distant metastasis-free survival and overall survival rates were 89%, 74% and 66%, respectively. No treatment-related deaths occurred. Grade 3-4 toxicities of mucositis, nausea/vomiting and leukopenia were observed in 34%, 4% and 4% of the patients, respectively. In conclusion, further improvement in survival and locoregional control is necessary, although our regimen showed acceptable toxicities.

  7. First-line chemotherapy with cisplatin plus fractionated temozolomide in recurrent glioblastoma multiforme: a phase II study of the Gruppo Italiano Cooperativo di Neuro-Oncologia.

    PubMed

    Brandes, Alba A; Basso, Umberto; Reni, Michele; Vastola, Francesca; Tosoni, Alicia; Cavallo, Giovanna; Scopece, Luciano; Ferreri, Andres J; Panucci, Maria G; Monfardini, Silvio; Ermani, Mario

    2004-05-01

    Cisplatin and temozolomide (TMZ) are active in glioblastoma multiforme (GBM), with different profiles of toxicity. A bid regimen of TMZ achieves a strong inhibition of O(6)-alkylguanine DNA-alkyl transferase (AGAT), and cisplatin reduces AGAT activity in vitro, suggesting a possible synergic interaction. The primary end point of the present multicenter phase II study was progression-free survival (PFS) at 6 months (PFS-6); secondary end points included response, toxicity, and overall survival. Chemotherapy-naive patients with GBM who experienced disease recurrence or progression after surgery and standard radiotherapy were eligible. Chemotherapy cycles consisted of cisplatin 75 mg/m(2) on day 1, TMZ 130 mg/m(2) bolus followed by nine doses of 70 mg/m(2) every 12 hours (total of 5 days) from day 2 every 4 weeks. In the absence of hematologic toxicity, TMZ was escalated to 1,000 mg/m(2) in 5 days. A total of 50 patients (median age, 53.4 years; range, 27 to 70 years; median Karnofsky performance status, 80; range, 60 to 100) were accrued in the study. PFS-6 was 34% (95% CI, 23% to 50%), and PFS-12 was 4% (95% CI, 0.3% to 16%). Median PFS was 18.4 weeks (95% CI, 13 to 25.9 weeks). Among 49 assessable patients, one complete response and nine partial responses were obtained, with an overall response rate of 20.4% (95% CI, 7.7% to 33%). Among 203 treatment cycles delivered, the most common grade 3 or grade 4 events included granulocytopenia in 7.9% of cycles, thrombocytopenia in 4%, and neurologic toxicity in three patients (6%). The new cisplatin plus bid TMZ regimen appears active in chemotherapy-naive patients with recurrent GBM and incurs an acceptable toxicity.

  8. Epigallocatechin-3-gallate, a prototypic chemopreventative agent for protection against cisplatin-based ototoxicity

    PubMed Central

    Borse, Vikrant; Al Aameri, Raheem F H; Sheehan, Kelly; Sheth, Sandeep; Kaur, Tejbeer; Mukherjea, Debashree; Tupal, Srinivasan; Lowy, Michelle; Ghosh, Sumana; Dhukhwa, Asmita; Bhatta, Puspanjali; Rybak, Leonard P; Ramkumar, Vickram

    2017-01-01

    Cisplatin-induced ototoxicity is one of the major factors limiting cisplatin chemotherapy. Ototoxicity results from damage to outer hair cells (OHCs) and other regions of the cochlea. At the cellular level, cisplatin increases reactive oxygen species (ROS) leading to cochlear inflammation and apoptosis. Thus, ideal otoprotective drugs should target oxidative stress and inflammatory mechanisms without interfering with cisplatin's chemotherapeutic efficacy. In this study, we show that epigallocatechin-3-gallate (EGCG) is a prototypic agent exhibiting these properties of an effect otoprotective agent. Rats administered oral EGCG demonstrate reduced cisplatin-induced hearing loss, reduced loss of OHCs in the basal region of the cochlea and reduced oxidative stress and apoptotic markers. EGCG also protected against the loss of ribbon synapses associated with inner hair cells and Na+/K+ ATPase α1 in the stria vascularis and spiral ligament. In vitro studies showed that EGCG reduced cisplatin-induced ROS generation and ERK1/2 and signal transducer and activator of transcription-1 (STAT1) activity, but preserved the activity of STAT3 and Bcl-xL. The increase in STAT3/STAT1 ratio appears critical for mediating its otoprotection. EGCG did not alter cisplatin-induced apoptosis of human-derived cancer cells or cisplatin antitumor efficacy in a xenograft tumor model in mice because of its inability to rescue the downregulation of STAT3 in these cells. These data suggest that EGCG is an ideal otoprotective agent for treating cisplatin-induced hearing loss without compromising its antitumor efficacy. PMID:28703809

  9. Curative effect of paclitaxel and cisplatin combined chemotherapy on cervical cancer and its relation with tissue micro vascular and lymphatic vessels density.

    PubMed

    Gao, Zhi-Hui; Wang, Qian-Qing

    2015-09-01

    This study was to discuss the curative effect of paclitaxel and cisplatin combined chemotherapy on cervical cancer and its relation with tissue micro vascular and lymphatic vessels density. The combined chemotherapy of paclitaxel 135 mg/m² and cisplatin 25mg/m² were taken to observe the clinical curative effect. The postoperative paraffin tissue had been collected, had performed the LYVE-1 (lymphatic endothelium specific hyaluronan receptor-1) and CD31 immunohistochemical staining. The complete remission rate of high micro lymphatic vessels density group (was or more 6.0) and high micro vascular density group were obviously higher than in low micro lymphatic vessels density group and low micro vascular density group, the difference was statistically significance (P<0.05). This study further analyzed the relation of MVD and LVD with clinical pathological parameters. The difference was statistically significant (P<0.01). The curative effect of paclitaxel and cisplatin combined therapy was promising, positive and was closely related with cervical cancer tissue LVD and MVD. The LVD and MVD could be one of the predictors of early cervical CIN and early cervical cancer development.

  10. Stages III and IV Squamous Cell Carcinoma of the Mouth: Three-Year Experience with Superselective Intraarterial Chemotherapy Using Cisplatin Prior to Definitive Treatment

    SciTech Connect

    Hirai, Toshinori; Korogi, Yukunori; Hamatake, Satoshi; Nishimura, Ryuichi; Baba, Yuji; Takahashi, Mutsumasa; Uji, Yasuyoshi; Taen, Akira

    1999-05-15

    Purpose: This study was designed to assess the 3-year experience with superselective intraarterial chemotherapy prior to definitive treatment for stages III and IV squamous cell carcinomas of the mouth. Methods: Twenty-two patients prospectively received superselective intraarterial chemotherapy using relatively low-dose cisplatin via a transfemoral approach. The locations of the tumors were the tongue (n= 12), gingiva (n= 5), buccal mucosa (n= 2), hard palate (n= 1), floor of the mouth (n= 1), and lip (n= 1). After intraarterial chemotherapy, 21 patients underwent surgery (n= 14), radiation therapy (n= 6), or both (n= 1). The survival rate of 25 patients who underwent surgery with/without radiation therapy until 1992 at Kumamoto University Hospital was also evaluated as a historical control. The survival curve was calculated with the Kaplan-Meier method, and the statistical difference between survival curves was determined with the generalized Wilcoxon test. Results: The overall response rate was 95% [complete response (tumor completely resolved), 24%; partial response (tumor reduction {>=}50%), 71%]. Fifty-two intraarterial infusions were performed without any catheter-related complications. Mild and transient local toxicity such as edema or mucositis of the infused area was relatively common. One patient died of renal failure from cisplatin. After a median follow-up of 20 months (range 2-41 months), the estimated 3-year survival rate for patients who underwent intraarterial chemotherapy plus surgery was 91%. The survival of the patients who underwent intraarterial chemotherapy plus surgery tended to be longer than that of the historical control. Conclusions: Early tumor reduction without delay of subsequent treatments can be obtained by intraarterial chemotherapy while minimizing complications and possibly improving survival. Further investigations of long-term survival with larger series need to be performed.

  11. [The effect of combination chemotherapy to adapted to chronotherapy with 5-fluorouracil, leucovorin, mitomycin C and cisplatin in patients with gastric or colorectal cancer].

    PubMed

    Kamoshita, N; Yokomori, T; Iesato, H; Ohya, T; Nagaoka, H; Okabe, T; Kato, Y; Takeyoshi, I; Ohwada, S; Morishita, Y

    2000-05-01

    We performed combination chemotherapy adapted to chronotherapy with 5-fluorouracil, leucovorin, mitomycin C and cisplatin in 11 patients with gastric cancer and 7 with colorectal cancer. Treatment consisted of a 5-day course of continuous arterial or intravenous infusion of 5-FU (500 mg/body/day), arterial or intravenous infusion of leucovorin (20 mg/body/day) at 6:00 p.m. on days 1-5, arterial or intravenous infusion of mitomycin C (2 mg/body) at 9:00 a. m. on day 5, and arterial or intravenous infusion of cisplatin (20-80 mg/body) at 6:00 p.m. on day 5. The effective rate against gastric cancer was 73%; however, the effective rate against colorectal cancer was 29%. During and after this therapy, there was only a little appetite loss, nausea and stomatitis.

  12. Adjuvant chemotherapy in patients with completely resected non-small cell lung cancer

    PubMed Central

    2014-01-01

    Adjuvant chemotherapy has been established as a standard for patients with completely resected non-small cell lung cancer (NSCLC). Adjuvant chemotherapy increased the 5-year survival rates by 4% to 15% within randomized trials and, based on a meta-analysis of five cisplatin-based trials, by 5.4%. Adjuvant chemotherapy consists of a cisplatin-based doublet, preferentially cisplatin plus vinorelbine. Future improvements in outcome of adjuvant therapy are expected by customized chemotherapy and the integration of targeted therapies or immunotherapy. PMID:25806316

  13. miR-125b-5p enhances chemotherapy sensitivity to cisplatin by down-regulating Bcl2 in gallbladder cancer

    PubMed Central

    Yang, Dong; Zhan, Ming; Chen, Tao; Chen, Wei; Zhang, Yunhe; Xu, Sunwang; Yan, Jinchun; Huang, Qihong; Wang, Jian

    2017-01-01

    Gallbladder cancer represents the most common malignancy of the biliary tract and is highly lethal with less than 5% overall 5-year survival rate. Chemotherapy remains the major treatment for late-stage patients. However, insensitivity to these chemotherapeutic agents including cisplatin is common. MicroRNAs (miRNAs) have been shown as modulators of drug resistance in many cancer types. We used genome-wide gene expression analysis in clinical samples to identify miR-125b-5p down-regulated in gallbladder cancer. miR-125b-5p up-regulation promoted cell death in gallbladder cancer cells in the presence of cisplatin. In contrast, knockdown of miR-125b-5p reduced cell death in gallbladder cancer cells treated with cisplatin. Up-regulation of miR-125b-5p significantly decreased tumor growth in combination with cisplatin in a mouse model. We identified Bcl2 as a direct target of miR-125b-5p which mediates the function of miR-125b-5p in gallbladder cancer. In clinical samples, miR-125b-5p was down-regulated in gallbladder cancer whereas Bcl2 was up-regulated and their expression was inversely correlated. Moreover, low miR-125b-5p expression or high expression of Bcl2 is correlated with poor prognosis in gallbladder cancer. Taken together, our findings indicate that miR-125b-5p is a potent chemotherapy sensitizer and may function as a new biomarker for the prognosis of gallbladder cancer patients. PMID:28256505

  14. Enhancement of Intratumoral Chemotherapy with Cisplatin with or without Microwave Ablation and Lipiodol. Future Concept for Local Treatment in Lung Cancer

    PubMed Central

    Hohenforst-Schmidt, Wolfgang; Zarogoulidis, Paul; Stopek, Joshua; Kosmidis, Efstratios; Vogl, Thomas; Linsmeier, Bernd; Tsakiridis, Kosmas; Lampaki, Sofia; Lazaridis, George; Mpakas, Andreas; Browning, Robert; Papaiwannou, Antonis; Drevelegas, Antonis; Baka, Sofia; Karavasilis, Vasilis; Mpoukovinas, Ioannis; Turner, J Francis; Zarogoulidis, Konstantinos; Brachmann, Johannes

    2015-01-01

    Novel therapies for lung cancer are being explored nowadays with local therapies being the tip of the arrow. Intratumoral chemotherapy administration and local microwave ablation have been investigated in several studies. It has been previously proposed that lipiodol has the ability to modify the microenvironment matrix. In our current study we investigated this theory in BALBC mice. In total 160 BALBC mice were divided in eight groups: a) control, b) cisplatin, c) microwave, d) microwave and lipiodol, e) cisplatin and lipiodol, f) microwave and cisplatin, g) lipiodol and h) lipiodol, cisplatin and microwave. Lewis lung carcinoma cell lines (106) were injected into the right back leg of each mouse. After the 8th day, when the tumor volume was about 100mm3 the therapy application was initiated, once per week for four weeks. Magnetic resonance imaging was performed for each tumor when a mouse died or when sacrificed if they were still alive by the end of the experiment (8-Canal multifunctional spool; NORAS MRI products, Gmbh, Germany). Imaging and survival revealed efficient tumor apoptosis for the groups b,c,d,e and f. However; severe toxicity was observed in group h and no follow up was available for this group after the second week of therapy administration. Lipiodol in its current form does assist in a more efficient way the distribution of cisplatin, as the microwave apoptotic effect. Future modification of lipiodol might provide a more efficient method of therapy enhancement. Combination of drug and microwave ablation is possible and has an efficient apoptotic effect. PMID:25663938

  15. Enhancement of Intratumoral Chemotherapy with Cisplatin with or without Microwave Ablation and Lipiodol. Future Concept for Local Treatment in Lung Cancer.

    PubMed

    Hohenforst-Schmidt, Wolfgang; Zarogoulidis, Paul; Stopek, Joshua; Kosmidis, Efstratios; Vogl, Thomas; Linsmeier, Bernd; Tsakiridis, Kosmas; Lampaki, Sofia; Lazaridis, George; Mpakas, Andreas; Browning, Robert; Papaiwannou, Antonis; Drevelegas, Antonis; Baka, Sofia; Karavasilis, Vasilis; Mpoukovinas, Ioannis; Turner, J Francis; Zarogoulidis, Konstantinos; Brachmann, Johannes

    2015-01-01

    Novel therapies for lung cancer are being explored nowadays with local therapies being the tip of the arrow. Intratumoral chemotherapy administration and local microwave ablation have been investigated in several studies. It has been previously proposed that lipiodol has the ability to modify the microenvironment matrix. In our current study we investigated this theory in BALBC mice. In total 160 BALBC mice were divided in eight groups: a) control, b) cisplatin, c) microwave, d) microwave and lipiodol, e) cisplatin and lipiodol, f) microwave and cisplatin, g) lipiodol and h) lipiodol, cisplatin and microwave. Lewis lung carcinoma cell lines (10(6)) were injected into the right back leg of each mouse. After the 8th day, when the tumor volume was about 100mm(3) the therapy application was initiated, once per week for four weeks. Magnetic resonance imaging was performed for each tumor when a mouse died or when sacrificed if they were still alive by the end of the experiment (8-Canal multifunctional spool; NORAS MRI products, Gmbh, Germany). Imaging and survival revealed efficient tumor apoptosis for the groups b,c,d,e and f. However; severe toxicity was observed in group h and no follow up was available for this group after the second week of therapy administration. Lipiodol in its current form does assist in a more efficient way the distribution of cisplatin, as the microwave apoptotic effect. Future modification of lipiodol might provide a more efficient method of therapy enhancement. Combination of drug and microwave ablation is possible and has an efficient apoptotic effect.

  16. Syndrome of inappropriate antidiuretic hormone secretion following irinotecan-cisplatin administration as a treatment for recurrent ovarian clear cell carcinoma.

    PubMed

    Kwon, Do Youn; Han, Gwan Hee; Ulak, Roshani; Ki, Kyung Do; Lee, Jong Min; Lee, Seon Kyung

    2017-01-01

    Syndrome of inappropriate antidiuretic hormone secretion (SIADH) has various causes including central nervous system disorders, pulmonary and endocrine diseases, paraneoplastic syndromes, and use of certain drugs. SIADH induced by chemotherapy with irinotecan-cisplatin is not a common complication. Here, we review a case of SIADH after treatment with irinotecan-cisplatin. A 45-year-old woman received adjuvant chemotherapy (paclitaxel-carboplatin) for ovarian clear cell carcinoma, but the cancer recurred within 9 months of chemotherapy. Subsequently, a second line of combination chemotherapy containing irinotecan-cisplatin was initiated. However, 5 days after chemotherapy administration, her general condition began to deteriorate; her hematological tests revealed hyponatremia. Therefore, it is imperative to consider the possibility of SIADH in patients being treated with irinotecan-cisplatin-based chemotherapy. Proper monitoring of serum sodium levels and assessment of clinical symptoms should be performed in such patients for early diagnosis and prompt management.

  17. [Combination chemotherapy with bleomycin, vinca alkaloid and cisplatin (BVP) for advanced urothelial cancer].

    PubMed

    Sekine, H; Fukui, I; Yamada, T; Takeuchi, S; Tachibana, Y; Yokokawa, M

    1984-08-01

    Since October 1979, 18 patients with metastatic urothelial cancer have been treated with combination chemotherapy of bleomycin (5-10 mg/day administered on days 1 to 7), vinca alkaloid (vinblastine 5-10 mg/day or vincristine 1 mg/sqm on days 8 and 9) and CDDP (60 mg/sqm on day 10). CR was achieved in 3 of the 18 patients and PR in 6 patients. Over-all, the response rate was 50%. Among 3 patients who achieved CR, 2 patients are still free of disease for 31 months and for 28 months, and the other is alive with cancer for 26 months. The 2-year survival rate was 58% in responders (CR + PR) and 0% in nonresponders. (p less than 0.005). In many cases, the response was observed after the first or second course of BVP therapy, and there was a relatively good response in patients with lymphnode metastasis alone. The treatment was tolerated well and common toxic effects were nausea, vomiting of moderate to severe degree (100%), myelosuppression (50%) and mild nephrotoxicity (22%). As to the choice of vinca alkaloids, vincristine seemed to be the treatment of choice because it was less toxic than vinblastine and was almost equally effective.

  18. Adjuvant platinum-based chemotherapy for early stage cervical cancer

    PubMed Central

    Rosa, Daniela D; Medeiros, Lídia RF; Edelweiss, Maria I; Pohlmann, Paula R; Stein, Airton T

    2014-01-01

    Background This is an updated version of the original Cochrane review published in The Cochrane Library 2009, Issue 3. Most women with early cervical cancer (stages I to IIA) are cured with surgery or radiotherapy, or both. We performed this review originally because it was unclear whether cisplatin-based chemotherapy after surgery, radiotherapy or both, in women with early stage disease with risk factors for recurrence, was associated with additional survival benefits or risks. Objectives To evaluate the effectiveness and safety of platinum-based chemotherapy after radical hysterectomy, radiotherapy, or both in the treatment of early stage cervical cancer. Search methods For the original 2009 review, we searched the Cochrane Gynaecological Cancer Group Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library 2009, Issue 1), MEDLINE, EMBASE, LILACS, BIOLOGICAL ABSTRACTS and CancerLit, the National Research Register and Clinical Trials register, with no language restriction. We handsearched abstracts of scientific meetings and other relevant publications. We extended the database searches to November 2011 for this update. Selection criteria Randomised controlled trials (RCTs) comparing adjuvant cisplatin-based chemotherapy (after radical surgery, radiotherapy or both) with no adjuvant chemotherapy, in women with early stage cervical cancer (stage IA2-IIA) with at least one risk factor for recurrence. Data collection and analysis Two review authors extracted data independently. Meta-analysis was performed using a random-effects model, with death and disease progression as outcomes. Main results For this updated version, we identified three additional ongoing trials but no new studies for inclusion. Three trials including 368 evaluable women with early cervical cancer were included in the meta-analyses. The median follow-up period in these trials ranged from 29 to 42 months. All women had undergone surgery first. Two trials

  19. Neuropeptide Y protects kidney against cisplatin-induced nephrotoxicity by regulating p53-dependent apoptosis pathway.

    PubMed

    Kim, Namoh; Min, Woo-Kie; Park, Min Hee; Lee, Jong Kil; Jin, Hee Kyung; Bae, Jae-Sung

    2016-05-01

    Cisplatin is a platinum-based chemotherapeutic drug for treating various types of cancers. However, the use of cisplatin is limited by its negative effect on normal tissues, particularly nephrotoxicity. Various mechanisms such as DNA adduct formation, mitochondrial dysfunction, oxidative stress, and apoptosis are involved in the adverse effect induced by cisplatin treatment. Several studies have suggested that neuropeptide Y (NPY) is involved in neuroprotection as well as restoration of bone marrow dysfunction from chemotherapy induced nerve injury. However, the role of NPY in chemotherapy- induced nephrotoxicity has not been studied. Here, we show that NPY rescues renal dysfunction by reducing the expression of pro-apoptotic proteins in cisplatin induced nephrotoxicity through Y1 receptor, suggesting that NPY can protect kidney against cisplatin nephrotoxicity as a possible useful agent to prevent and treat cisplatin-induced nephrotoxicity. [BMB Reports 2016; 49(5): 288-292].

  20. Role of olanzapine in chemotherapy-induced nausea and vomiting on platinum-based chemotherapy patients: a randomized controlled study.

    PubMed

    Mukhopadhyay, Sandip; Kwatra, Gagandeep; Alice K, Pamela; Badyal, Dinesh

    2017-01-01

    Even with the use of modern antiemetic drugs, chemotherapy-induced nausea and vomiting (CINV) is still a cause of great distress to the patients. Olanzapine, primarily marketed as an antipsychotic, was found to reduce nausea and vomiting in some chemotherapy patients. But it was never tested in Indian population with a diverse genetic background. The present study aims to evaluate the role of olanzapine in CINV in patients receiving platinum-based chemotherapy. The study was a randomized, controlled, assessor-blinded study on 100 chemotherapy-naïve consenting patients receiving any one from cisplatin, carboplatin or oxaliplatin. The control group (n = 50) received palonosetron and dexamethasone in the approved therapeutic dose from the day 1 of chemotherapy. The test group (n = 50) received additional olanzapine 10 mg/day from day 1 for five consecutive days. CINV and quality of life (QoL) were assessed. Vomiting was significantly less among the olanzapine-treated patients. Control of delayed emesis was significantly better in this group (complete response among 96 vs. 42 % in the control group, p value <0.0001). Incidence and severity of nausea was significantly less in this group. Failure of anti-CINV measure was 4 % in this group compared to 26 % of the patients of the control group during overall days 1-5. Though sedation was more in these olanzapine-treated patients, there was no dose-limiting adverse event. Quality of life was also better among the olanzapine-treated patients. Olanzapine was found to be effective as add-on in the control of CINV.

  1. An Adsorptive Transfer Technique Coupled with Brdicka Reaction to Reveal the Importance of Metallothionein in Chemotherapy with Platinum Based Cytostatics

    PubMed Central

    Krizkova, Sona; Fabrik, Ivo; Huska, Dalibor; Adam, Vojtech; Babula, Petr; Hrabeta, Jan; Eckschlager, Tomas; Pochop, Pavel; Darsova, Denisa; Kukacka, Jiri; Prusa, Richard; Trnkova, Libuse; Kizek, Rene

    2010-01-01

    The drugs based on platinum metals represent one of the oldest, but also one of the most effective groups of chemotherapeutic agents. Thanks to many clinical studies it is known that resistance of tumor cells to drugs is a frequent cause of chemotherapy failure. With regard to platinum based drugs, multidrug resistance can also be connected with increased expression of low-molecular weight protein metallothionein (MT). This study aimed at investigating the interactions of MT with cisplatin or carboplatin, using the adsorptive transfer technique coupled with differential pulse voltammetry Brdicka reaction (AdTS DPV Brdicka reaction), and a comparison of in vitro results with results obtained in vivo. The results obtained from the in vitro study show a strong affinity between platinum based drugs and MT. Further, we analyzed extracts of neuroblastoma cell lines treated with cisplatin or carboplatin. It is clear that neuroblastoma UKF-NB-4 cisplatin-resistant and cisplatin-sensitive cell lines unlikely respond to the presence of the platinum-based cytostatics cisplatin and carboplatin. Finally, we determined the level of MT in samples from rabbits treated with carboplatin and patients with retinoblastoma treated with the same drug. PMID:21614176

  2. Chemotherapy

    MedlinePlus

    ... during chemotherapy. Chemotherapy is most often given in cycles. These cycles may last 1 day, several days, or a ... period when no chemotherapy is given between each cycle. A rest period may last for days, weeks, ...

  3. Feasibility and Efficacy of Induction Docetaxel, Cisplatin, and 5-Fluorouracil Chemotherapy Combined With Cisplatin Concurrent Chemoradiotherapy for Nonmetastatic Stage IV Head-and-Neck Squamous Cell Carcinomas

    SciTech Connect

    Prestwich, Robin J.; Oeksuez, Didem Colpan; Dyker, Karen; Coyle, Catherine; Sen, Mehmet

    2011-11-15

    Purpose: To report the experience of treating selected fit patients with locally advanced head-and-neck squamous cell carcinoma with three cycles of induction TPF (docetaxel 75 mg/m{sup 2}, cisplatin 75 mg/m{sup 2}, 5-fluorouracil 750 mg/m{sup 2}, Days 2-5) followed by concurrent three-weekly bolus cisplatin 100 mg/m{sup 2} chemoradiotherapy. Methods and Materials: Between March 2006 and February 2010, 66 patients with nonmetastatic Stage IV head-and-neck squamous cell carcinoma were treated in a single institution with three cycles of induction TPF, followed by radical radiotherapy with concurrent cisplatin 100 mg/m{sup 2}. Results: Median age was 54 years (range, 33-69 years). Median follow-up was 21 months (range, 4-55 months). During TPF, Grade 3 toxicity occurred in 18 patients (27%), dose modifications in 10 (15%), delays in 3 (5%), and unplanned admissions in 6 (9%); a clinical tumor response was documented in 60 patients (91%). Median time from the final cycle of TPF to commencing radiotherapy was 22 days. Sixty-two patients (94%) received radical radiotherapy, and all completed treatment with no delays {>=}3 days. One, two, and three cycles of concurrent cisplatin were delivered to 18 patients (29%), 38 patients (61%), and 3 patients (5%), respectively. Ninety-two percent of patients received enteral feeding; median weight loss during treatment was 7%. Forty-two patients (68%) had unplanned admissions with no on-treatment deaths. Three unrelated deaths occurred after treatment. At 1 year after treatment, 21% of patients without disease progression remained gastrostomy dependent. Of 58 assessable patients, 50 (86%) achieved a complete response after treatment. One- and 2-year progression-free survival, cause-specific survival, and overall survival were 88%, 92%, and 86% and 80%, 85%, and 80%, respectively. Conclusion: The combination of induction TPF with concurrent cisplatin chemoradiotherapy in patients with locally advanced head and neck squamous cell

  4. [A case of cardiac tamponade due to malignant pericarditis with lung adenocarcinoma, effectively treated with pericardial drainage and pemetrexed plus cisplatin chemotherapy].

    PubMed

    Yoshida, Kazufumi; Teramoto, Shinji

    2015-01-01

    A 68-year-old man was diagnosed with non small cell lung cancer in May 2013. Although the patient was negative for EGFR mutation, he wished to undergo treatment with gefitinib and erlotinib as first-line therapy. However, one year later, he was admitted to our hospital because of cardiac tamponade due to malignant pericarditis. He received pericardial drainage, after which his condition was stabilized. He was diagnosed with lung adenocarcinoma by cytology of pericardial effusion and treated with pemetrexed plus cisplatin as second-line therapy. Thereafter, the malignant effusion was decreased and the primary lesion was regressed. He received six courses of chemotherapy, however, brain metastases and bone metastases appeared. The brain metastases were controlled with gamma knife radiosurgery and he received carboptatin-paclitaxel plus bevacizumab as third-line therapy. The patient is currently receiving chemotherapy without any recurrence of malignant pericarditis or cardiac tamponade.

  5. Cisplatin intrastrand adducts sensitize DNA to base damage by hydrated electrons.

    PubMed

    Behmand, B; Wagner, J R; Sanche, L; Hunting, D J

    2014-05-08

    The oligonucleotide TTTTTGTGTTT with or without a cisplatin adduct was reacted with hydrated electrons generated by ionizing radiation. Hydroxyl radicals were quenched with ethylenediaminetetraacetic acid (EDTA), and the solutions were bubbled with wet nitrogen to eliminate oxygen, a scavenger of hydrated electrons. Prior to irradiation, the structure of the initial cisplatin adduct was identified by mass spectrometry as G-cisplatin-G. Radiation damage to DNA bases was quantified by high-performance liquid chromatography (HPLC), after enzymatic digestion of the TTTTTGTGTTT-cisplatin complex to deoxyribonucleosides. The masses of the platinum adducts following digestion and separation by HPLC were measured by mass spectrometry. Our results demonstrate that hydrated electrons induce damage to thymines as well as detachment of the cisplatin moiety from both guanines in the oligonucleotide. This detachment regenerates both unmodified guanine and damaged guanine, in equimolar amounts. At 1000 Gy, a net average of 2.5 thymines and 1 guanine are damaged for each platinum lost from the oligonucleotide. Given the extensive base damage that occurs for each cisplatin adduct lost, it is clear that, prior to undergoing detachment, these adducts must catalyze several cycles of reactions of hydrated electrons with DNA bases. It is likely that a single reaction leads to the loss of the cisplatin adduct and the damage observed on the guanine base; however, the damage to the thymine bases must require the continued presence of the cisplatin adduct, acting as a catalyst. To our knowledge, this is the first time that platinum-DNA adducts have been shown to have catalytic activity. We propose two pathways for the interaction of hydrated electrons with TTTTTGTGTTT-cisplatin: (1) the hydrated electron is initially captured by a thymine base and transferred by base to base electron hopping to the guanine site, where the cisplatin moiety detaches from the oligonucleotide via dissociative

  6. Nonmetastatic osteosarcoma of the extremity. Neoadjuvant chemotherapy with methotrexate, cisplatin, doxorubicin and ifosfamide. An Italian Sarcoma Group study (ISG/OS-Oss).

    PubMed

    Ferrari, Stefano; Meazza, Cristina; Palmerini, Emanuela; Tamburini, Angela; Fagioli, Franca; Cozza, Raffaele; Ferraresi, Virginia; Bisogno, Gianni; Mascarin, Maurizio; Cefalo, Graziella; Manfrini, Marco; Capanna, Rodolfo; Biagini, Roberto; Donati, Davide; Picci, Piero

    2014-01-01

    Based on the results of the ISG/OS-1 study, the MAP regimen (methotrexate [MTX], doxorubicin [ADM] and cisplatin [CDP] with the addition of ifosfamide [IFO] in poor-responder patients) was investigated in patients with nonmetastatic osteosarcoma of the extremity (ISG/OS-Oss study). Compared with the ISG/OS-1 study (cumulative doses: ADM 420 mg/m(2), MTX 120 g/m(2), CDP 600 mg/m(2), IFO 30 g/m(2)), the ISG/OS-Oss study reduced the number of MTX cycles from 10 to 5 (cumulative MTX dose: 60 g/m(2)) in order to diminish treatment duration and toxicity. From January 2007 to June 2011, 171 patients (median age 16 years, 60% males) were registered. The limb salvage rate was 94% and the good pathologic response rate 51% (these figures were 92% and 48%, respectively, in the ISG/OS-1 study). At a median follow-up of 39 months (range, 4-80), the 5-year overall survival rate was 80% (95% CI, 73%-87%) and the event-free survival was 50% (95% CI, 39%-59%). For comparison, the 5-year overall and event-free survival rates in ISG/OS-1 were 73% (95% CI, 65%-81%) and 64% (95% CI, 56%-73%), respectively. This study confirms that in nonmetastatic osteosarcoma of the extremity, conservative surgery in more than 90% and a good pathologic response rate of 50% can be expected with primary chemotherapy based on the MAP regimen. The response and resection rates in the ISG/OS-Oss study are in the same range as those of the previous study, whereas the event-free survival is lower than that previously achieved. Since the only difference between the two studies was the cumulative dose of postoperatively given MTX, our data support the importance of the cumulative dose of MTX in the MAP regimen.

  7. Chemotherapy with cisplatin or carboplatin in combination with etoposide for small-cell esophageal cancer: a systemic analysis of case series.

    PubMed

    Gao, R; Zhang, Y; Wen, X P; Fu, J; Zhang, G J

    2014-01-01

    Chemotherapy has been the first-choice treatment for small-cell esophageal cancer (SCEC), etoposide plus cisplatin or carboplatin (EP/CP) is the most commonly recommended chemotherapeutical strategy. However, the choice of chemotherapy in treating SCEC has not been validated by studies of large cohorts of cases because of the rarity of the malignancy, and the efficacy superiority of EP/CP over other chemotherapy combinations has not been confirmed. The present case series analysis was conducted to address the above issues. Reported studies of SCEC patients were retrieved. Case series with more than five patients were enrolled. Eight patients treated in our institute were also included as another case series. Data pertaining to clinical stages, treatment regimens, and survival time were collected and analyzed. Altogether, 19 SCEC case series were enrolled, including 164 male and 61 female patients with a median age of 63.5 years. The follow-up time ranged from 0.1 to 221 months (median 12.3 months). The median survival time (MST) was 19 months for limited disease (LD) patients (124 cases) and 9 months for extensive disease (ED) patients (88 cases) (P<0.001). For LD patients, MST was obviously prolonged by chemotherapeutical regimens (20 vs. 10 months, P<0.01), whereas this superiority was not proved in ED patients (10 vs. 10 months, P>0.05). EP/CP did not result in significantly longer MST, compared with that of the cases treated by other chemotherapy combinations (P>0.05, for either LD or ED cases). Chemotherapy prolongs the survival time of the LD SCEC patients, which indicates that chemotherapeutical treatment is effective for SCEC. EP/CP, as commonly recommended multidrug chemotherapy regimen, is not superior to other chemotherapy combinations. © 2013 Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

  8. Genetic Determinants of Cisplatin Resistance in Patients With Advanced Germ Cell Tumors.

    PubMed

    Bagrodia, Aditya; Lee, Byron H; Lee, William; Cha, Eugene K; Sfakianos, John P; Iyer, Gopa; Pietzak, Eugene J; Gao, Sizhi Paul; Zabor, Emily C; Ostrovnaya, Irina; Kaffenberger, Samuel D; Syed, Aijazuddin; Arcila, Maria E; Chaganti, Raju S; Kundra, Ritika; Eng, Jana; Hreiki, Joseph; Vacic, Vladimir; Arora, Kanika; Oschwald, Dayna M; Berger, Michael F; Bajorin, Dean F; Bains, Manjit S; Schultz, Nikolaus; Reuter, Victor E; Sheinfeld, Joel; Bosl, George J; Al-Ahmadie, Hikmat A; Solit, David B; Feldman, Darren R

    2016-11-20

    Purpose Owing to its exquisite chemotherapy sensitivity, most patients with metastatic germ cell tumors (GCTs) are cured with cisplatin-based chemotherapy. However, up to 30% of patients with advanced GCT exhibit cisplatin resistance, which requires intensive salvage treatment, and have a 50% risk of cancer-related death. To identify a genetic basis for cisplatin resistance, we performed whole-exome and targeted sequencing of cisplatin-sensitive and cisplatin-resistant GCTs. Methods Men with GCT who received a cisplatin-containing chemotherapy regimen and had available tumor tissue were eligible to participate in this study. Whole-exome sequencing or targeted exon-capture-based sequencing was performed on 180 tumors. Patients were categorized as cisplatin sensitive or cisplatin resistant by using a combination of postchemotherapy parameters, including serum tumor marker levels, radiology, and pathology at surgical resection of residual disease. Results TP53 alterations were present exclusively in cisplatin-resistant tumors and were particularly prevalent among primary mediastinal nonseminomas (72%). TP53 pathway alterations including MDM2 amplifications were more common among patients with adverse clinical features, categorized as poor risk according to the International Germ Cell Cancer Collaborative Group (IGCCCG) model. Despite this association, TP53 and MDM2 alterations predicted adverse prognosis independent of the IGCCCG model. Actionable alterations, including novel RAC1 mutations, were detected in 55% of cisplatin-resistant GCTs. Conclusion In GCT, TP53 and MDM2 alterations were associated with cisplatin resistance and inferior outcomes, independent of the IGCCCG model. The finding of frequent TP53 alterations among mediastinal primary nonseminomas may explain the more frequent chemoresistance observed with this tumor subtype. A substantial portion of cisplatin-resistant GCTs harbor actionable alterations, which might respond to targeted therapies. Genomic

  9. Risk Factors for Nephrotoxicity Associated with Cisplatin

    PubMed Central

    Almanric, Karine; Marceau, Nathalie; Cantin, Ariane; Bertin, Émilie

    2017-01-01

    Background Cisplatin-induced nephrotoxicity occurs in about one-third of patients who receive this chemotherapy drug. In late 2012, the study institution began measuring serum creatinine on day 7 after administration of cisplatin to identify patients with acute renal failure. Objective To evaluate the extent of nephrotoxicity associated with cisplatin and the influence of risk factors for nephrotoxicity. Methods This retrospective study involved patients who received a first cycle of cisplatin-based chemotherapy between November 1, 2012, and November 1, 2013. Patients’ medical records were reviewed to determine the increase in creatinine level (graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events) and the influence of certain prespecified risk factors, such as age, concomitant medications, initial dose of cisplatin, and related medical conditions. Results Among the 80 patients evaluated, 14 (17%) experienced no increase in the level of serum creatinine (grade 0), 44 (55%) experienced a grade 1 increase, 19 (24%) a grade 2 increase, and 3 (4%) a grade 3 increase; no patients experienced a grade 4 increase. Patients with the greatest risk of a grade 2 or 3 increase were those treated with hydrochlorothiazide (odds ratio [OR] 9.35, 95% confidence interval [CI] 2.49 to 35.14) or an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker (OR 5.02, 95% CI 1.76 to 14.32). After adjustment, only hydrochlorothiazide was associated with an increased risk of nephrotoxicity (OR 5.39, 95% CI 1.04 to 28.07). Among patients taking hydrochlorothiazide, the average incremental increase in serum creatinine was 59.9 μmol/L (95% CI 34.3 to 85.4 μmol/L). Conclusions Taking hydrochlorothiazide was associated with a significant increase in serum creatinine following cisplatin therapy. On the basis of these results, patients should stop taking hydrochlorothiazide before undergoing cisplatin-based chemotherapy. PMID

  10. Cisplatin induces stemness in ovarian cancer

    PubMed Central

    Thiagarajan, Praveena S.; Rao, Vinay S.; Hale, James S.; Gupta, Nikhil; Hitomi, Masahiro; Nagaraj, Anil Belur; DiFeo, Analisa; Lathia, Justin D.; Reizes, Ofer

    2016-01-01

    The mainstay of treatment for ovarian cancer is platinum-based cytotoxic chemotherapy. However, therapeutic resistance and recurrence is a common eventuality for nearly all ovarian cancer patients, resulting in poor median survival. Recurrence is postulated to be driven by a population of self-renewing, therapeutically resistant cancer stem cells (CSCs). A current limitation in CSC studies is the inability to interrogate their dynamic changes in real time. Here we utilized a GFP reporter driven by the NANOG-promoter to enrich and track ovarian CSCs. Using this approach, we identified a population of cells with CSC properties including enhanced expression of stem cell transcription factors, self-renewal, and tumor initiation. We also observed elevations in CSC properties in cisplatin-resistant ovarian cancer cells as compared to cisplatin-naïve ovarian cancer cells. CD49f, a marker for CSCs in other solid tumors, enriched CSCs in cisplatin-resistant and -naïve cells. NANOG-GFP enriched CSCs (GFP+ cells) were more resistant to cisplatin as compared to GFP-negative cells. Moreover, upon cisplatin treatment, the GFP signal intensity and NANOG expression increased in GFP-negative cells, indicating that cisplatin was able to induce the CSC state. Taken together, we describe a reporter-based strategy that allows for determination of the CSC state in real time and can be used to detect the induction of the CSC state upon cisplatin treatment. As cisplatin may provide an inductive stress for the stem cell state, future efforts should focus on combining cytotoxic chemotherapy with a CSC targeted therapy for greater clinical utility. PMID:27105520

  11. NHERF1 Enhances Cisplatin Sensitivity in Human Cervical Cancer Cells

    PubMed Central

    Tao, Tao; Yang, Xiaomei; Qin, Qiong; Shi, Wen; Wang, Qiqi; Yang, Ying; He, Junqi

    2017-01-01

    Cervical cancer is one of the most common female malignancies, and cisplatin-based chemotherapy is routinely utilized in locally advanced cervical cancer patients. However, resistance has been the major limitation. In this study, we found that Na+/H+ Exchanger Regulatory Factor 1 (NHERF1) was downregulated in cisplatin-resistant cells. Analysis based on a cervical cancer dataset from The Cancer Genome Atlas (TCGA) showed association of NHERF1 expression with disease-free survival of patients received cisplatin treatment. NHERF1 overexpression inhibited proliferation and enhanced apoptosis in cisplatin-resistant HeLa cells, whereas NHERF1 knockdown had inverse effects. While parental HeLa cells were more resistant to cisplatin after NHERF1 knockdown, NHERF1 overexpression in CaSki cells promoted cisplatin sensitivity. Overexpression and knockdown studies also showed that NHERF1 significantly inhibited AKT and extracellular signal–regulated kinase (ERK) signaling pathways in cisplatin-resistant cells. Taken together, our results provide the first evidence that NHERF1 can sensitize cisplatin-refractory cervical cancer cells. This study may help to increase understanding of the molecular mechanisms underlying cisplatin resistance in tumors. PMID:28085111

  12. Amphiphilic oligomer-based micelles as cisplatin nanocarriers for cancer therapy

    NASA Astrophysics Data System (ADS)

    Qi, Xiuxiu; Li, Najun; Gu, Hongwei; Xu, Yujie; Xu, Ying; Jiao, Yang; Xu, Qingfeng; Li, Hua; Lu, Jianmei

    2013-09-01

    Polymeric micelles (~10 nm) have been prepared from the amphiphilic oligomer comprising oligomeric polystyrene as the hydrophobic inner core and half of EDTA (-N(CH2COOH)2) as the hydrophilic outermost shell. After chelating cisplatin with -N(CH2COOH)2 in water, polymeric micelles containing Pt on the spherical surface have been easily obtained. Since the chelate group is introduced into the amphiphilic oligomer as the terminal group by a RAFT agent, the chelation of cisplatin with PS(COOH)2 is almost stoichiometric. The drug carrier based on PS(COOH)2 showed a high loading efficiency (>70%) towards cisplatin. The release of the therapeutic Pt from the cisplatin-loaded composites (PS(COOH)2-Pt) triggered under weak acidic conditions resulted in good Pt-release and accumulation in tumor cells. Both in vitro and in vivo, the chelated cisplatin inhibited Sk-Br3 cancer more effectively than the intact cisplatin does. Furthermore, neither PS(COOH)2 nor PS(COOH)2-Pt showed obvious systematic toxicity.Polymeric micelles (~10 nm) have been prepared from the amphiphilic oligomer comprising oligomeric polystyrene as the hydrophobic inner core and half of EDTA (-N(CH2COOH)2) as the hydrophilic outermost shell. After chelating cisplatin with -N(CH2COOH)2 in water, polymeric micelles containing Pt on the spherical surface have been easily obtained. Since the chelate group is introduced into the amphiphilic oligomer as the terminal group by a RAFT agent, the chelation of cisplatin with PS(COOH)2 is almost stoichiometric. The drug carrier based on PS(COOH)2 showed a high loading efficiency (>70%) towards cisplatin. The release of the therapeutic Pt from the cisplatin-loaded composites (PS(COOH)2-Pt) triggered under weak acidic conditions resulted in good Pt-release and accumulation in tumor cells. Both in vitro and in vivo, the chelated cisplatin inhibited Sk-Br3 cancer more effectively than the intact cisplatin does. Furthermore, neither PS(COOH)2 nor PS(COOH)2-Pt showed obvious

  13. Prospective randomized double-blind multicentre phase II study comparing gemcitabine and cisplatin plus sorafenib chemotherapy with gemcitabine and cisplatin plus placebo in locally advanced and/or metastasized urothelial cancer: SUSE (AUO-AB 31/05).

    PubMed

    Krege, Susanne; Rexer, Heidrun; vom Dorp, Frank; de Geeter, Patrick; Klotz, Theodor; Retz, Margitte; Heidenreich, Axel; Kühn, Michael; Kamradt, Joern; Feyerabend, Susan; Wülfing, Christian; Zastrow, Stefan; Albers, Peter; Hakenberg, Oliver; Roigas, Jan; Fenner, Martin; Heinzer, Hans; Schrader, Mark

    2014-03-01

    To evaluate the efficacy and safety of gemcitabine and cisplatin in combination with sorafenib, a tyrosine-kinase inhibitor, compared with chemotherapy alone as first-line treatment in advanced urothelial cancer. The study was a randomized phase II trial. Its primary aim was to show an improvement in progression-free survival (PFS) of 4.5 months by adding sorafenib to conventional chemotherapy. Secondary objectives were objective response rate (ORR), overall survival (OS) and toxicity. The patients included in the trial had histologically confirmed locally advanced and/or metastatic urothelial cancer of the bladder or upper urinary tract. Chemotherapy with gemcitabine (1250 mg/qm on days 1 and 8) and cisplatin (70 mg/qm on day 1) repeated every 21 days, was administered to all patients in a double-blind randomization of additional sorafenib (400 mg twice daily) vs placebo (two tablets twice daily) on days 3-21. Treatment continued until progression or unacceptable toxicity, the maximum number of cycles was limited to eight. The response assessment was repeated after every two cycles. Between October 2006 and October 2010, 98 of 132 planned patients were recruited. Nine patients were ineligible. The final analysis included 40 patients in the sorafenib and 49 patients in the placebo arm. There were no significant differences between the two arms concerning ORR (sorafenib: complete response [CR] 12.5%, partial response [PR] 40%; placebo: CR 12%, PR 35%), median PFS (sorafenib: 6.3 months, placebo: 6.1 months) or OS (sorafenib: 11.3 months, placebo: 10.6 months). Toxicity was moderately higher in the sorafenib arm. Diarrrhoea occurred significantly more often in the sorafenib arm and hand-foot syndrome occurred only in the sorafenib arm. The study was closed prematurely because of slow recruitment. Although the addition of sorafenib to standard chemotherapy showed acceptable toxicity, the trial failed to show a 4.5 months improvement in PFS. © 2013 The Authors

  14. Comparison of Ifosfamide, Carboplatin and Etoposide versus Etoposide, Steroid, and Cytarabine Cisplatin as Salvage Chemotherapy in Patients with Refractory or Relapsed Hodgkin's lymphoma

    PubMed Central

    Mehrzad, Valiollah; Ashrafi, Farzaneh; Farrashi, Ali Reza; Pourmarjani, Reyhaneh; Dehghani, Mehdi; Shahsanaei, Armindokht

    2017-01-01

    Background: Refractory or relapsed Hodgkin's disease (HD) occurs in 10-50% of patients. The treatment of choice for these patients is high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT). Response to salvage chemotherapy (SCT) partial remission (PR) is necessary before HDCT with ASCT. However, its applicability is restricted mostly to patients responding to salvage chemotherapy. Optimal salvage regimen for these patients is unclear. In this study, our aim was to compare the efficacy profiles of ifosfamide, carboplatin, and etoposide (ICE) and etoposide-steroid-cytarabine-cisplatin (ESHAP) (cytosine arabinoside, cisplatin, and dexamethasone) regimens in the salvage treatment of relapsed or refractory HD. Materials and Methods: In this retrospective analysis, 114 patients with primary refractory or relapsed HD who received ICE or ESHAP salvage regimen were included. Results: Of 114 patients, 47 (41.2%) were females and the median age was 31.5 years. Response could be evaluated in 114 patients. Of 114 patients, 38 (33%) achieved complete remission (CR) and 21 (18.4%) achieved PR, leading to an overall response rate (ORR: CR + PR) of 51.4%. In the evaluable ICE group (n = 41), rates of CR, PR, and ORR were 21.9%, 17.1%, and 39% and in the ESHAP group (n = 73), rates of CR, PR, and ORR were 39.7%, 19.2%, and 58.9% (for ORR, P = 0.04), respectively. Conclusion: In patients with relapsed or refractory HD, treatment with ESHAP seems to have higher rates of response than ICE regimen does.

  15. Chemotherapy

    Cancer.gov

    Chemotherapy is a type of cancer treatment that uses drugs to kill cancer cells. Learn how chemotherapy works against cancer, why it causes side effects, and how it is used with other cancer treatments.

  16. Chemotherapy

    MedlinePlus

    ... people. But knowing what chemotherapy is, how it works, and what to expect can often help calm your fears. It can also give you a better sense of control over your cancer treatment. ... Drugs Work CancerQuest: Chemotherapy [video] Interactive Chemotherapy Program from Emmi ...

  17. Combination chemotherapy of alternating etoposide and carboplatin with weekly administration of irinotecan and cisplatin in extensive-stage small-cell lung cancer.

    PubMed

    Yoshimura, Akinobu; Noro, Rintaro; Miyanaga, Akihiko; Mizutani, Hideaki; Kosaihira, Seiji; Minegishi, Yuji; Seike, Masahiro; Hino, Mitsunori; Ando, Masahiro; Nomura, Koichiro; Okano, Tetsuya; Kobayashi, Kunihiko; Gemma, Akihiko

    2012-10-01

    A phase II study was conducted to determine the tumor efficacy and tolerance of alternating chemotherapy in extensive-stage small-cell lung cancer (ED-SCLC). Thirty-six patients with previously untreated ED-SCLC were enrolled in the study. At least four courses of chemotherapy consisting of alternation of two drug combinations were given: alternating cycles of etoposide and carboplatin (EC) with weekly administration of irinotecan and cisplatin (IP) at 3- or 4-week intervals. The overall response rate was 81.8%. The median duration of survival and progression-free survival were 314 days and 144 days, respectively. Hematological toxicity was the main adverse event. Grade 3 or 4 neutropenia, thrombocytopenia and anemia were observed in 69.2, 25.6 and 23.1% of the patients, respectively. Severe diarrhea (10.8%) was remarkable during the IP regimen. This novel alternating chemotherapy for patients with ED-SCLC showed moderate tumor efficacy and an acceptable safety profile.

  18. Preconditioning chemotherapy with paclitaxel and cisplatin enhances the antitumor activity of cytokine induced-killer cells in a murine lung carcinoma model.

    PubMed

    Huang, Xiang; Huang, Guichun; Song, Haizhu; Chen, Longbang

    2011-08-01

    Adoptive cell therapy involving the use of ex vivo generated cytokine-induced killer cells (CIKs) provides a promising approach to immunotherapy. However, the therapeutic activity of CIKs is limited by the immunosuppressive factors active in the host. It has become increasingly apparent that manipulation of the recipient immune system with the preconditioning regimen is essential to guarantee the antitumor effect of subsequent adoptive cell therapy. In our study, paclitaxel (PTX) and cisplatin (DDP) were used as preconditioning drugs combined with CIKs to illustrate the potential mechanisms underlying the synergic antitumor effect against Lewis lung cancer cells in vitro and in vivo. We found that 3LL cells displayed an increased sensitization to CIKs-induced lysis after treatment with PTX or DDP in vitro. Significant inhibition of tumor growth was observed in mice treated with combinatorial chemo-immunotherapy with respect to untreated or single regimen treated ones. Prior chemotherapy markedly enhanced the intratumoral accumulation of CD3(+) T lymphocytes and the homing of CIKs to the spleen and tumor. Moreover, the frequencies of intratumoral and splenic regulatory T cells (Tregs) were significantly decreased after chemotherapy pretreatment. Our findings provide a new rationale for combining immunotherapy and chemotherapy to induce a synergistic antitumor response in patients with lung cancer. Copyright © 2010 UICC.

  19. Ten Years of Complete Remission of Pulmonary Metastasis after Post-Cystectomy Palliative Cisplatin-Gemcitabine Chemotherapy with Gefitinib for Muscle Invasive Bladder Cancer: A Case Report.

    PubMed

    Fahmy, Omar; Scharpf, Marcus; Schubert, Tina; Feyerabend, Susan; Stenzl, Arnulf; Schwentner, Christian; Fend, Falko; Gakis, Georgios

    2016-01-01

    Muscle-invasive bladder cancer (MIBC) is considered one of the most lethal malignancies with high metastatic potential. Usually, metastatic bladder cancer carries worse prognosis with a median survival rate of approximately 6 months, which can be prolonged for up to 14 months with palliative systemic chemotherapy. We present the case of a 61-year-old male patient diagnosed with localized MIBC 10 years ago. He underwent nerve-sparing radical cystectomy with ileal neobladder, but developed pulmonary metastatic disease 7 months postoperatively. Six cycles of gemcitabine/cisplatin combination chemotherapy with an addition of gefitinib as daily oral medication were administered within a randomized phase II clinical trial; this resulted in complete remission of the pulmonary metastases. Until now, the patient is still on gefitinib daily without any side effects. Although, the addition of gefitinib to standard systemic chemotherapy has not been shown to improve the survival in metastatic urothelial cancer, this case represents a very pleasant albeit uncommon long-term outcome. © 2016 S. Karger AG, Basel.

  20. [Neoadjuvant, inductive or adjuvant chemotherapy of bladder cancer].

    PubMed

    Ohlmann, C-H; De Santis, M

    2013-11-01

    Perioperative chemotherapy is a standard treatment for patients with muscle-invasive bladder carcinoma undergoing radical cystectomy; however, direct comparisons of neoadjuvant and adjuvant chemotherapy are lacking. Evidence-based data and implementation into daily clinical practice favor neoadjuvant chemotherapy; nevertheless, neoadjuvant chemotherapy is still underused in daily practice compared to adjuvant chemotherapy. If neoadjuvant chemotherapy has not been used and patients are fit enough to receive cisplatin, adjuvant chemotherapy should be considered in patients with pT3-pT4 and/or lymph node metastases.

  1. Mechanisms of cisplatin-induced muscle atrophy

    SciTech Connect

    Sakai, Hiroyasu; Sagara, Atsunobu; Arakawa, Kazuhiko; Sugiyama, Ryoto; Hirosaki, Akiko; Takase, Kazuhide; Jo, Ara; Sato, Ken; Chiba, Yoshihiko; Yamazaki, Mitsuaki; Matoba, Motohiro; Narita, Minoru

    2014-07-15

    Fatigue is the most common side effect of chemotherapy. However, the mechanisms of “muscle fatigue” induced by anti-cancer drugs are not fully understood. We therefore investigated the muscle-atrophic effect of cisplatin, a platinum-based anti-cancer drug, in mice. C57BL/6J mice were treated with cisplatin (3 mg/kg, i.p.) or saline for 4 consecutive days. On Day 5, hindlimb and quadriceps muscles were isolated from mice. The loss of body weight and food intake under the administration of cisplatin was the same as those in a dietary restriction (DR) group. Under the present conditions, the administration of cisplatin significantly decreased not only the muscle mass of the hindlimb and quadriceps but also the myofiber diameter, compared to those in the DR group. The mRNA expression levels of muscle atrophy F-box (MAFbx), muscle RING finger-1 (MuRF1) and forkhead box O3 (FOXO3) were significantly and further increased by cisplatin treated group, compared to DR. Furthermore, the mRNA levels of myostatin and p21 were significantly upregulated by the administration of cisplatin, compared to DR. On the other hand, the phosphorylation of Akt and FOXO3a, which leads to the blockade of the upregulation of MuRF1 and MAFbx, was significantly and dramatically decreased by cisplatin. These findings suggest that the administration of cisplatin increases atrophic gene expression, and may lead to an imbalance between protein synthesis and protein degradation pathways, which would lead to muscle atrophy. This phenomenon could, at least in part, explain the mechanism of cisplatin-induced muscle fatigue. - Highlights: • Cisplatin decreased mass and myofiber diameter in quadriceps muscle. • The mRNA of MAFbx, MuRF1 and FOXO3 were increased by the cisplatin. • The mRNA of myostatin and p21 were upregulated by cisplatin. • The phosphorylation of Akt and FOXO3a was decreased by cisplatin.

  2. Dose responsive effects of cisplatin in L02 cells using NMR-based metabolomics.

    PubMed

    Liu, Shu; Wang, Wei; Zhou, Xueyi; Gu, Runhuan; Ding, Zongli

    2014-01-01

    Cisplatin is an effective chemotherapeutic agent for the treatment of various cancers, such as bladder cancer, epithelial ovarian cancer, cervical cancer, and so on. However, cisplatin can cause various side effects. In this study, the dose-responsive effects of cisplatin were investigated in an in vitro model of human liver cells (L02) using NMR-based metabolomics. The inverted U-shaped curve of cell proliferation confirmed the hormetic effects of cisplatin (from 1 nM to 1 mM) in L02 cells. However, the metabolite changes revealed both U-shaped (ethanol, lactate, aspartate, choline, etc.) and inverted U-shaped (glutamate, glutamine, 4-aminobutyrate, myo-inositol, etc.) curves induced by three typical concentrations of cisplatin which covered the inverted U-shaped curve as indicated by the cell proliferation assay. These findings suggested that a macroscopic hormesis phenomenon on the cell proliferation could be reflected by both stimulated and inhibited metabolites and corresponding metabolic pathways to cisplatin treatments. Therefore, a global analysis using metabolomics may give a broader view into the dose-response relationship than using a single endpoint at molecular levels.

  3. Platinum-based Chemotherapy in Primary Advanced Seminoma—a Retrospective Analysis: Treatment Results at the Northern Israel Oncology Center (1989–2010)

    PubMed Central

    Stein, Moshe E.; Drumea, Karen; Charas, Tomer; Gershuny, Anthony; Ben-Yosef, Rahamim

    2014-01-01

    Objective: Over the past 30 years, great strides have been made in the treatment of disseminated testicular tumors. Despite the low number of patients and the rarity of studies concerning primary advanced seminoma, the efficacy of chemotherapy is clear, mainly 3–4-cisplatin-based chemotherapy. Aiming to contribute to the understanding and implementation of proper chemotherapeutic management in advanced seminoma patients, we retrospectively summarized our experience with 26 patients who were referred for platinum-based chemotherapy, post-orchiectomy to the Northern Israel Oncology Center between 1989 and 2010. Response rate, side effects, and long-term outcome were investigated. Methods: Before chemotherapy, meticulous staging was done, including tumor markers (B-human chorionic gonadotropin (B-HCG), alpha-fetoprotein (AFP), and lactic dehydrogenase (LDH)), and abdominal and pelvic computerized tomography (CT) scans were carried out. Results: All 26 treated patients achieved complete remission, clinically and symptomatically, with normalization of their CT scans. At a median follow-up of 120 months (range, 24–268 months) all patients are alive, without evidence of recurrent disease. One patient whose disease recurred twice achieved a third complete remission following salvage treatment with high-dose chemotherapy and autologous peripheral stem cell transplantation. Another patient, who preferred surveillance, relapsed abdominally after 9 months but achieved long-standing complete remission with cisplatin-based chemotherapy. Both these patients are alive with no evidence of disease. Three patients recovered uneventfully from bleomycin-induced pneumonitis. Conclusions: Advanced seminoma is a highly curable disease using platinum-based chemotherapy. Our study confirms the efficacy and safety of cisplatin-based chemotherapy in the treatment of advanced seminoma. PMID:24498512

  4. Concurrent IMRT and weekly cisplatin followed by GDP chemotherapy in newly diagnosed, stage IE to IIE, nasal, extranodal NK/T-Cell lymphoma.

    PubMed

    Ke, Q-H; Zhou, S-Q; Du, W; Liang, G; Lei, Y; Luo, F

    2014-12-12

    On the basis of the benefits of frontline radiation in early-stage, extranodal natural killer (NK)/T-cell lymphoma (ENKTL), we conducted the trial of concurrent chemoradiotherapy (CCRT) followed by three cycles of gemcitabine, dexamethasone and cisplatin (GDP). Thirty-two patients with newly diagnosed, stage IE to IIE, nasal ENKTL received CCRT (that is, all patients received intensity-modulated radiotherapy 56 Gy and cisplatin 30 mg/m(2) weekly, 3-5 weeks). Three cycles of GDP (gemcitabine 1000 mg/m(2) intravenously (i.v.) on days 1 and 8, dexamethasone 40 mg orally on days 1-4 and cisplatin 75 mg/m(2) i.v. on day 1 (GDP), every 21 days as an outpatient were scheduled after CCRT. All patients completed CCRT, which resulted in 100% response that included 24 complete responses (CRs) and eight partial responses. The CR rate after CCRT was 75.0% (that is, 24 of 32 responses). Twenty-eight of the 32 patients completed the planned three cycles of GDP, whereas four patients did not because they withdrew (n = 1) or because they had an infection (n = 3). The overall response rate and the CR rate were 90.6% (that is, 29 of 32 responses) and 84.4% (that is, 27 of 32 responses), respectively. Only two patient experienced grade 3 toxicity during CCRT (nausea), whereas 13 of the 30 patients experienced grade 4 neutropenia. The estimated 3-year overall survival and progression-free rates were 87.50% and 84.38%, respectively. In conclusion, CCRT followed by GDP chemotherapy can be a feasible and effective treatment strategy for stage IE to IIE nasal ENKTL.

  5. Phase I Trial of Triapine-Cisplatin-Paclitaxel Chemotherapy for Advanced Stage or Metastatic Solid Tumor Cancers.

    PubMed

    Kunos, Charles A; Chu, Edward; Makower, Della; Kaubisch, Andreas; Sznol, Mario; Ivy, Susan Percy

    2017-01-01

    Ribonucleotide reductase (RNR) is an enzyme involved in the de novo synthesis of deoxyribonucleotides, which are critical for DNA replication and DNA repair. Triapine is a small-molecule RNR inhibitor. A phase I trial studied the safety of triapine in combination with cisplatin-paclitaxel in patients with advanced stage or metastatic solid tumor cancers in an effort to capitalize on disrupted DNA damage repair. A total of 13 patients with various previously treated cancers were given a 96-h continuous intravenous (i.v.) infusion of triapine (40-120 mg/m(2)) on day 1, and then 3-h i.v. paclitaxel (80 mg/m(2)) followed by 1-h i.v. cisplatin (50-75 mg/m(2)) on day 3. This combination regimen was repeated every 21 days. The maximum tolerated dose (MTD) for each agent was identified to be triapine (80 mg/m(2)), cisplatin (50 mg/m(2)), and paclitaxel (80 mg/m(2)). Common grade 3 or 4 toxicities included reversible anemia, leukopenia, thrombocytopenia, or electrolyte abnormalities. The combination regimen of triapine-cisplatin-paclitaxel resulted in no objective responses; however, five (83%) of six patients treated at the MTD had stable disease between 1 and 8 months duration. This phase I study showed that the combination regimen of triapine-cisplatin-paclitaxel was safe and provides a rational basis for a follow-up phase II trial to evaluate efficacy and progression-free survival in women with metastatic or recurrent uterine cervix cancer.

  6. Combination chemotherapy with carmustine and cisplatin followed by procarbazine, lomustine, and vincristine for adult high-grade astrocytoma.

    PubMed

    Liau, Chi-Ting; Wei, Kuo-Chen; Tseng, Chen-Kan; Jung, Shih-Ming

    2005-01-01

    We have reported that carmustine (BCNU) and cisplatin administered before, during, and after radiotherapy did not improve the survival of patients with high-grade astrocytomas and were associated with more serious toxicities than radiotherapy plus BCNU. In an attempt to improve survival, we studied a combination regimen procarbazine, lomustine, and vincristine (PCV) after radiotherapy in addition to BCNU and cisplatin during radiotherapy. From 1994 through 1998, 42 patients were enrolled in the study. Of these, 20 had glioblastoma multiforme and 22 had anaplastic astrocytoma. The patients had a median age of 48.5 years. All patients had subtotal or total resection, or biopsy as the initial procedure. Then, all patients were treated with BCNU and cisplatin concurrently during radiotherapy followed by PCV after radiotherapy. The median time to follow up for survivors was 13.8 months (range, 1.7-108.2 months). The median time to tumor progression was 7.2 months (range, 0-88.7 months) and median survival time was 13.3 months (range, 1.7-88.7 months). The only factor that had a conventionally significant effect on the overall survival was resectability. Patients who had received subtotal/total resection had a longer median survival compared with patients who had received biopsy only (18.0 vs. 9.5 months). This combined modality treatment program was associated with reversible grade 3 to 4 hematological toxicity in 10 patients, with grade 3 ototoxicity in one patient and grade 2 neurotoxicity in one patient. A combination of BCNU and cisplatin with cranial irradiation followed by PCV was moderately toxic and appeared to offer no obvious survival advantages compared with radiotherapy plus BCNU and cisplatin alone.

  7. Capecitabine and cisplatin chemotherapy (XP) alone or sequentially combined chemoradiotherapy containing XP regimen in patients with three different settings of stage IV esophageal cancer.

    PubMed

    Lee, Sung Sook; Kim, Sung-Bae; Park, Seung-Il; Kim, Yong Hee; Ryu, Jin-Sook; Song, Ho-Yong; Shin, Ji Hoon; Jung, Hwoon Yong; Lee, Gin Hyug; Choi, Kee Don; Cho, Kyung-Ja; Kim, Jong Hoon

    2007-11-01

    The 1997 staging system for esophageal carcinoma subdivided distant metastatic disease (M1) into nonregional lymph node metastases (M1a) and other metastases (M1b). To determine the relevance of this classification system, we investigated the efficacy and toxicity of capecitabine/cisplatin (XP) chemotherapy alone or in combination with radiotherapy. We identified 74 patients with M1 disease treated at Asan Medical Center from January 2003 to December 2005. Of these patients, 19 (25.7%) were classified as M1a, 29 (39.2%) as M1b (nonvisceral lymph node metastases), and 26 (35.1%) as M1b (visceral metastases). All patients were treated with first two cycles of XP induction chemotherapy, consisting of capecitabine 1000 mg/m(2) twice daily on days 1-14, and i.v. cisplatin 60 mg/m(2) on day 1, every 3 weeks. Patients classified as M1a and M1b (nonvisceral lymph node metastases) were treated with 54 Gy of radiotherapy, concurrently with weekly capecitabine 800 mg/m(2) twice daily on days 1-5 and i.v. cisplatin 30 mg/m(2) on day 1 during radiation. Patients classified as M1b (visceral metastases) were treated with chemotherapy only until disease progression or intolerance to chemotherapy. In response to the first two cycles of chemotherapy, 3/18 (16.7%) M1a nonregional lymph node (LN), 4/27 (14.8%) M1b nonvisceral LN metastases and 5/25 (20%) M1b visceral metastases patients attained partial responses. After definitive chemoradiation in the setting of M1a, M1b nonvisceral LN metastases and maximum cycles of chemotherapy in the M1b visceral metastases setting, the response rates were 77.8, 62.9 and 36.0% respectively. With median follow-up of 12.5 months (range 0.5-22.8), 50 of 74 patients (67.5%) died. The median time to progression (TTP) was 7.8 months (95% CI, 6.0-9.5 months) and the median overall survival (OS) was 12.0 months (95% CI, 9.0-15.0 months). Median TTP in the M1a, M1b nonvisceral LN metastases and M1b visceral metastases were 10.3, 6.5 and 5.9 months

  8. Increased procoagulant activity of red blood cells in the presence of cisplatin.

    PubMed

    Lü, Cheng-fang; Yu, Hong-juan; Hou, Jin-xiao; Zhou, Jin

    2008-09-20

    Cisplatin based chemotherapy is a well recognized risk factor for coagulation disorders and thrombosis. The pathophysiological mechanisms by which cisplatin promote thrombosis are not well understood. Red blood cells (RBCs) were separated from peripheral blood of patients with breast cancer (n = 10) and healthy adults (n = 6) and treated with cisplatin. Coagulation time of RBCs was assessed by one step recalcification time and the productions of thrombin, intrinsic and extrinsic factor Xa were measured in the presence or absence of various concentrations of lactadherin. Exposed phosphatidylserine was stained with lactadherin and observed by confocal microscopy and flow cytometry. Neither fresh RBCs nor RBCs treated without cisplatin had potent procoagulant activity. Cisplatin treatment increased procoagulant activity of RBCs in a cell number- and concentration-dependent manner. Exposed phosphatidylserine was stained with lactadherin and after cisplatin treatment, strong fluorescence was revealed by confocal microscopy. Lactadherin bound RBCs from patients with breast cancer increased from (1.9 +/- 0.5)% on control RBCs to (68.0 +/- 3.5)% on RBCs treated with 10 micromol/L cisplatin for 24 hours. Cisplatin treatment increases procoagulant activity of RBCs, which have a strong association with exposure of phosphatidylserine. The increased procoagulant activity may contribute to the pathogenesis of thrombophilia during cisplatin based chemotherapy in breast cancer patients.

  9. Systemic cisplatin exposure during infancy and adolescence causes impaired cognitive function in adulthood

    PubMed Central

    Lomeli, Naomi; Bota, Daniela A.

    2017-01-01

    Cancer survivors diagnosed during infancy and adolescence may be at risk for chemotherapy-related cognitive impairments (CRCI), however the effects of pediatric chemotherapy treatment on adulthood cognitive function are not well understood. Impairments in memory, attention and executive function affect 15–50% of childhood leukemia survivors related to methotrexate exposure. Systemic cisplatin is used to treat a variety of childhood and adult cancers, yet the risk and extent of cognitive impairment due to platinum-based chemotherapy in pediatric patients is unknown. Systemic cisplatin penetrates the CNS, induces hippocampal synaptic damage, and leads to neuronal and neural stem/progenitor cell (NSC) loss. Survivors of non-leukemic cancers may be at risk for significant cognitive impairment related to cisplatin-driven neurotoxicity. We sought to examine the long-term effects of systemic cisplatin administration on cognitive function when administered during infancy and adolescence in a rat model. We performed cognitive testing in adult rats exposed to systemic cisplatin during either infancy or adolescence. Rats treated as adolescents showed significantly poor retrieval of a novel object as compared to controls. Further, cisplatin-treated infants and adolescents showed poor contextual discrimination as compared to controls, and an impaired response to cued fear conditioning. Ultimately, systemic cisplatin exposure resulted in more profound impairments in cognitive function in rats treated during adolescence than in those treated during infancy. Further, exposure to cisplatin during adolescence affected both hippocampus and amygdala dependent cognitive function, suggesting a more global cognitive dysfunction at this age. PMID:27851909

  10. Antibody-drug conjugates: targeting melanoma with cisplatin encapsulated in protein-cage nanoparticles based on human ferritin.

    PubMed

    Falvo, Elisabetta; Tremante, Elisa; Fraioli, Rocco; Leonetti, Carlo; Zamparelli, Carlotta; Boffi, Alberto; Morea, Veronica; Ceci, Pierpaolo; Giacomini, Patrizio

    2013-12-21

    A novel antibody-drug conjugate (ADC) was synthesized incorporating ferritin-based nanoparticles. An average of three molecules of monoclonal antibody (mAb) Ep1 to the human melanoma-specific antigen CSPG4 were conjugated to a single ferritin cage encapsulating about 50 cisplatin molecules (HFt-Pt-Ep1). The HFt-Pt-Ep1 nanoparticle had an estimated molecular size of about 900 kD and 33 nm, and flow cytometry demonstrated specific binding to a CSPG4(+) melanoma cell line, but not to a CSPG4(-) breast carcinoma cell line. As compared to the cisplatin-containing ferritin nanoparticle alone (HFt-Pt), which inhibited thymidine incorporation more efficiently in breast carcinoma than melanoma cells, the mAb-derivatized HFt-Pt-Ep1 nanoparticle had a 25-fold preference for the latter. A similar preference for melanoma was observed upon systemic intravenous administration of HFt-Pt-Ep1 to nude mice xenotransplanted with pre-established, palpable melanoma and breast carcinoma tumors. Thus, we have been able to determine precise combinations and stoichiometric relationships between mAbs and nanoparticle protein cages, whereby the latter lose their tropism for ubiquitously distributed cellular receptors, and acquire instead remarkably lineage-selective binding. HFt-Pt-Ep1 is therefore an interesting model to improve the therapeutic index of antiblastic therapy in a tumor such as melanoma, which at its advanced stages is totally refractory to mono- and combination-chemotherapy.

  11. Syndrome of inappropriate antidiuretic hormone secretion following irinotecan-cisplatin administration as a treatment for recurrent ovarian clear cell carcinoma

    PubMed Central

    Kwon, Do Youn; Han, Gwan Hee; Ulak, Roshani; Lee, Jong Min; Lee, Seon Kyung

    2017-01-01

    Syndrome of inappropriate antidiuretic hormone secretion (SIADH) has various causes including central nervous system disorders, pulmonary and endocrine diseases, paraneoplastic syndromes, and use of certain drugs. SIADH induced by chemotherapy with irinotecan-cisplatin is not a common complication. Here, we review a case of SIADH after treatment with irinotecan-cisplatin. A 45-year-old woman received adjuvant chemotherapy (paclitaxel-carboplatin) for ovarian clear cell carcinoma, but the cancer recurred within 9 months of chemotherapy. Subsequently, a second line of combination chemotherapy containing irinotecan-cisplatin was initiated. However, 5 days after chemotherapy administration, her general condition began to deteriorate; her hematological tests revealed hyponatremia. Therefore, it is imperative to consider the possibility of SIADH in patients being treated with irinotecan-cisplatin–based chemotherapy. Proper monitoring of serum sodium levels and assessment of clinical symptoms should be performed in such patients for early diagnosis and prompt management. PMID:28217682

  12. Co-administration of dexamethasone increases severity and accelerates onset day of neutropenia in bladder cancer patients on methotrexate, vinblastine, adriamycin and cisplatin chemotherapy: a retrospective cohort study.

    PubMed

    Itai, Shingo; Suga, Yukio; Hara, Yusuke; Izumi, Kouji; Maeda, Yuji; Kitagawa, Yasuhide; Ishizaki, Junko; Shimada, Tsutomu; Mizokami, Atsushi; Sai, Yoshimichi

    2017-01-01

    Bladder cancer patients receiving methotrexate, vinblastine, adriamycin and cisplatin (MVAC) chemotherapy are co-administered with dexamethasone as an anti-emetic. We examined whether or not dexamethasone affects the severity and onset day of MVAC-induced severe neutropenia. This was a retrospective study of bladder cancer patients treated with MVAC chemotherapy with or without dexamethasone as an antiemetic at Kanazawa University Hospital during January 2005 - December 2009. Patients were categorized into three groups; no dexamethasone use (Dex (-)), dexamethasone on day 2 (Dex 1 day), and dexamethasone on days 2, 3 and 4 (Dex multiday). We evaluated the incidence of grade 3/4 neutropenia and the day of onset of first severe neutropenic episode during the first course of MVAC chemotherapy. Logistic regression was used to investigate whether co-administration of dexamethasone was a risk factor for severe neutropenia. Episodes of grade 3/4 neutropenia occurred in 3 out of 6 (50.0%), 11 out of 12 (91.7%) and 6 out of 6 (100%) patients in the Dex (-), Dex 1 day, and Dex multiday groups, respectively. The appearance day of first severe neutropenia in the Dex multiday group (13.2 ± 1.0) was significantly accelerated compared to the Dex (-) group (17.7 ± 2.1). Univariate logistic regression analysis revealed that dexamethasone is a risk factor for severe neutropenia (OR 17.0; 95%CI: 1.3-223.1). Co-administration of dexamethasone for anti-emesis brings forward the first appearance of neutropenia, and increases the severity of neutropenia, in bladder cancer patients receiving MVAC chemotherapy.

  13. Inhibition of PKCδ reduces cisplatin-induced nephrotoxicity without blocking chemotherapeutic efficacy in mouse models of cancer

    PubMed Central

    Pabla, Navjotsingh; Dong, Guie; Jiang, Man; Huang, Shuang; Kumar, M. Vijay; Messing, Robert O.; Dong, Zheng

    2011-01-01

    Cisplatin is a widely used cancer therapy drug that unfortunately has major side effects in normal tissues, notably nephrotoxicity in kidneys. Despite intensive research, the mechanism of cisplatin-induced nephrotoxicity remains unclear, and renoprotective approaches during cisplatin-based chemotherapy are lacking. Here we have identified PKCδ as a critical regulator of cisplatin nephrotoxicity, which can be effectively targeted for renoprotection during chemotherapy. We showed that early during cisplatin nephrotoxicity, Src interacted with, phosphorylated, and activated PKCδ in mouse kidney lysates. After activation, PKCδ regulated MAPKs, but not p53, to induce renal cell apoptosis. Thus, inhibition of PKCδ pharmacologically or genetically attenuated kidney cell apoptosis and tissue damage, preserving renal function during cisplatin treatment. Conversely, inhibition of PKCδ enhanced cisplatin-induced cell death in multiple cancer cell lines and, remarkably, enhanced the chemotherapeutic effects of cisplatin in several xenograft and syngeneic mouse tumor models while protecting kidneys from nephrotoxicity. Together these results demonstrate a role of PKCδ in cisplatin nephrotoxicity and support targeting PKCδ as an effective strategy for renoprotection during cisplatin-based cancer therapy. PMID:21633170

  14. Induction of autophagy counteracts the anticancer effect of cisplatin in human esophageal cancer cells with acquired drug resistance.

    PubMed

    Yu, Le; Gu, Chunping; Zhong, Desheng; Shi, Lili; Kong, Yi; Zhou, Zhitao; Liu, Shuwen

    2014-12-01

    Cisplatin-based chemotherapy frequently resulted in acquired resistance. The underpinning mechanism of such resistance remains obscure especially in relation to autophagic response. This study thus investigated the role of autophagy in the anticancer activity of cisplatin in human esophageal cancer cells with acquired cisplatin resistance. In response to cisplatin treatment, EC109 cells exhibited substantial apoptosis and senescence whereas cisplatin-resistant EC109/CDDP cells exhibited resistance. In this respect, cisplatin increased ERK phosphorylation whose inhibition by MEK inhibitor significantly attenuated the cytotoxic and cytostatic effect of cisplatin. Notably, cisplatin preferentially induces autophagy in EC109/CDDP cells but not in EC109 cells. Moreover, the induction of autophagy was accompanied by the suppression of mTORC1 activity. Abolition of autophagy by pharmacological inhibitors or knockdown of ATG5/7 re-sensitized EC109/CDDP cells. Co-administration of an autophagy inhibitor chloroquine and cisplatin significantly suppressed tumor growth whereas cisplatin monotherapy failed to elicit anticancer activity in nude mice xenografted with EC109/CDDP cells. To conclude, our data implicate autophagic response as a key mechanism of acquired resistance to cisplatin, suggesting that autophagy is a novel target to improve therapy efficiency of cisplatin toward human esophageal cancers with acquired resistance.

  15. Weekly nanoparticle albumin-bound paclitaxel in combination with cisplatin versus weekly solvent-based paclitaxel plus cisplatin as first-line therapy in Chinese patients with advanced esophageal squamous cell carcinoma

    PubMed Central

    Wang, Hai-ying; Yao, Zhi-hua; Tang, Hong; Zhao, Yan; Zhang, Xiao-san; Yao, Shu-na; Yang, Shu-jun; Liu, Yan-yan

    2016-01-01

    Objective More effective regimens for advanced esophageal squamous cell carcinoma (ESCC) are urgently needed. Therefore, a retrospective study concerning the efficacy and safety of nanoparticle albumin-bound paclitaxel plus cisplatin (nab-TP) versus solvent-based paclitaxel plus cisplatin (sb-TP) as a first-line therapy was conducted in Chinese patients with advanced ESCC. Methods From June 2009 to June 2015, 32 patients were treated with nab-paclitaxel (125 mg/m2) on the first and eighth days (30 minutes infusion) and cisplatin (75 mg/m2) on the second day every 21 days (nab-TP arm). Also, 43 patients were treated with solvent-based paclitaxel (80 mg/m2) intravenously on the first and eighth days and the same dose of cisplatin (sb-TP arm). The two groups were compared in terms of objective response rate (ORR), disease control rate, progression-free survival (PFS), overall survival (OS), and safety profile. OS and PFS were estimated using Kaplan–Meier methods to determine associations between chemotherapy regimens and survival outcomes. Results Nab-TP demonstrated a higher ORR (50% vs 30%; P=0.082) and disease control rate (81% vs 65%; P=0.124) than sb-TP. Median OS was similar for nab-TP and sb-TP (12.5 vs 10.7 months; P=0.269). However, nab-TP resulted in a longer median PFS (6.1 months [95% confidence interval: 5.3–6.9]) than sb-TP (5.0 months [95% confidence interval: 4.4–5.6]) (P=0.029). The most common adverse events included anemia, leukopenia, neutropenia, febrile neutropenia, and thrombocytopenia in both the groups and no statistically significant differences were observed between the groups. With statistically significant differences, significantly less grade ≥3 peripheral neuropathy, arthralgia, and myalgia occurred in the nab-TP arm (all P<0.05). Dose reduction, treatment delays, and second-line therapy were similar between the two regimens. There were no treatment-related deaths in either group. Conclusion Nab-paclitaxel plus cisplatin is found

  16. Quality-of-life evaluation during platinum-based neoadjuvant chemotherapies for urothelial carcinoma.

    PubMed

    Fukushi, Ken; Narita, Takuma; Hatakeyama, Shingo; Yamamoto, Hayato; Soma, Osamu; Matsumoto, Teppei; Tobisawa, Yuki; Yoneyama, Tohru; Imai, Atsushi; Yoneyama, Takahiro; Hashimoto, Yasuhiro; Koie, Takuya; Ohyama, Chikara

    2017-04-01

    Although quality of life (QOL) is one of the most important considerations in patients treated with anticancer therapies, desirable regimens for neoadjuvant chemotherapy including QOL in locally advanced urothelial carcinoma remain unclear. The present study evaluated the influence of neoadjuvant platinum-based chemotherapy on QOL in patients with locally advanced urothelial carcinoma. Between June 2013 and March 2016, 83 urothelial carcinoma patients who received two courses of neoadjuvant chemotherapy were enrolled in this prospective observational study. Neoadjuvant regimens included gemcitabine + cisplatin (GCis) or gemcitabine + carboplatin (GCb) therapies. As a primary endpoint, we assessed QOL changes in each group before and after chemotherapy using the Quality of Life questionnaire on days 1, 3, and 15 of each cycle. Secondary endpoints included toxicity, safety, weight loss, renal function decline, and tumor responses. QOL analyses were performed in 39 patients receiving GCis and in 44 patients receiving GCb. Appetite loss, role functioning, nausea/vomiting, physical, and fatigue deteriorated >10% from baseline in the GCis group but not in the GCb group. Constipation worsened, whereas scores for pain and emotional items improved in both groups. Objective response rates were 38.5 and 43.2% in the GCis and GCb groups, respectively. Both GCis and GCb regimens were feasible in terms of QOL. The GCb regimen may be associated with a better QOL status especially in regard to gastrointestinal symptoms.

  17. Histological complete response in a patient with advanced biliary tract cancer treated by gemcitabine/cisplatin/S-1 combination chemotherapy: A case report

    PubMed Central

    Matsubara, Tokuhiro; Nishida, Tsutomu; Tomimaru, Yoshito; Yamamoto, Masashi; Hayashi, Shiro; Nakajima, Sachiko; Fukui, Koji; Dono, Keizo; Adachi, Shiro; Ioka, Tatsuya; Kanai, Masashi; Inada, Masami

    2016-01-01

    A 68-year-old woman was referred to our hospital with increased levels of biliary enzymes. On imaging, the patient was diagnosed with unresectable intrahepatic biliary tract cancer (BTC) with invasion of the portal vein and para-aortic lymph node metastasis (cT3N1M1, cStage IVb) and underwent endoscopic biliary drainage for the biliary stricture prior to therapy. The patient was subsequently enrolled in a phase III randomized trial (UMIN000014371/NCT02182778) and randomly assigned to receive gemcitabine/cisplatin/S-1 (GCS) combination therapy intravenously at doses of 1,000 or 25 mg/m2 on day 1 and orally twice daily at a dose of 80 mg/m2 on days 1–7 every 2 weeks. After 12 cycles of scheduled therapy without uncontrollable adverse effects, the patient achieved a good partial response with chemotherapy. Computed tomography (CT) revealed a marked reduction of the primary and metastatic lesions. In addition,18F-fluorodeoxyglucose-positron emission tomography/CT revealed diminishing abnormal uptake and no macroscopic evidence of factors adversely affecting tumor resectability. Therefore, the patient underwent extended right hepatic lobectomy, lymph node dissection and left hepaticojejunostomy. Finally, histological examination of the resected tissues revealed no residual cancer cells, suggesting a pathologically complete response. We herein present the case of a patient with intrahepatic BTC who achieved a pathologically complete response following combination chemotherapy with GCS. PMID:28101354

  18. A phase III, multicenter randomized controlled trial of neo-adjuvant chemotherapy paclitaxel plus cisplatin versus surgery alone for stage IIA–IIIB esophageal squamous cell carcinoma

    PubMed Central

    Zheng, Yan; Liu, Xianben; Zhang, Ruixiang; Wang, Zongfei; Sun, Haibo; Liu, Shilei

    2017-01-01

    Background The survival benefits of neoadjuvant chemotherapy (NAC) for esophagus squamous cell carcinoma (ESCC) remains controversial. The surgical procedure was not well defined in NAC strategy, in past trials. The different surgical procedure and different levels of lymphadenectomy may decrease the survival benefits from NAC. The new chemotherapy regimen with paclitaxel is promising. The purpose of this study is to confirm the superiority of paclitaxel, cisplatin and McKeown esophagectomy with total two-field lymphadenectomy compared with surgery alone for ESCC. Methods A two-arm phase III trial was launched in June 2015. A total of 528 patients will be recruited from eight Chinese institutions within 2.5 years. The overall survival (OS) is the primary endpoint, and the secondary endpoints include disease-free survival (DFS), R0 resection rate, complication rate, perioperation mortality, days of hospitalization, quality of life (QOL), NAC response rate, pathologic response rate, toxicities of NAC, prognostic factors, predictive factors, progression-free survival (PFS), and adverse events. Discussion The study will provide the final conclusion of NAC for ESCC in China. Trial registration NCT02442440 (https://register.clinicaltrials.gov/). PMID:28203424

  19. Mitomycin-C- or Cisplatin-Based Chemoradiotherapy for Anal Canal Carcinoma: Long-Term Results

    SciTech Connect

    Olivatto, Luis O.; Cabral, Vania; Rosa, Arthur; Bezerra, Marcos; Santarem, Erick; Fassizoli, Ana; Castro, Leonaldson; Simoes, Jose Humberto; Small, Isabele A.; Ferreira, Carlos Gil

    2011-02-01

    Purpose: To evaluate the long-term efficacy of concurrent radiotherapy with mitomycin-C (MMC)-based or cisplatin (CP)-based combinations in a cohort of patients with locally advanced anal canal carcinoma. Methods and Materials: Between 1988 and 2000, 179 patients with locally advanced anal canal carcinoma were treated at the Instituto Nacional de Cancer with two cycles of chemotherapy during Weeks 1 and 5 of radiotherapy. 5-Fluorouracil (750 mg/m{sup 2} 120-hour infusion or 1,000 mg/m{sup 2} 96-hour infusion) plus CP (100 mg/m{sup 2}) on the first day of each cycle or MMC (10-15 mg/m{sup 2}) on the first day of Cycle 1 was administered concurrent with radiotherapy (total dose, 55-59.4 Gy). Of the 179 patients, 60% were included from a randomized trial initiated at the Instituto Nacional de Cancer in 1991 that compared concurrent chemoradiotherapy with MMC vs. CP. Results: The median follow-up for the whole chemoradiotherapy group was 83 months. The median patient age was 58 years, 57% had Stage T3-T4 tumors, and 35% had N-positive disease. The 5-year cumulative colostomy rate was not significantly different between the CP group (22%) and MMC group (29%; p = .28). The actuarial 10-year overall survival and disease-free survival rate for the CP group was 54% and 49% and for the MMC group was 52% and 53%, respectively (p = .32 and p = .92, respectively). On multivariate analysis, male gender (p = .042) and advanced Stage T3-T4 disease (p <.0001) were statistically significant for worse disease-free survival. Stage T3-T4 (p = .039) and N+ (p = .039) disease remained independently significant for overall survival. Conclusion: Long-term follow-up has confirmed the good results of chemoradiotherapy with CP plus 5-fluorouracil, which seem to provide results equivalent to those with MMC plus 5-fluorouracil.

  20. A comparative study of cisplatin-based definitive chemo-radiation in non-metastatic squamous cell carcinoma of the esophagus

    PubMed Central

    Mofid, Bahram; Razzaghdoust, Abolfazl; Kashi, Amir Shahram Yousefi; Mirzaei, Hamid Reza

    2016-01-01

    Introduction Esophageal cancer is the seventh most frequent malignancy in Iranian men and the fourth most common cancer in Iranian women. It is also among the 10 most frequent cancers in the world. Definitive chemo-radiation using cisplatin with 5-fluorouracil (5-FU) is known as the standard of care among various chemotherapy regimens used with esophageal cancer patients who are not eligible for surgery. Cisplatin with paclitaxel and cisplatin with irinotecan also have been used often during the past five years. The aim of this research was to compare overall survival (OS) and hematological toxicity rates between these regimens. Methods This single-institutional study included 55 patients who were treated with definitive chemo-radiation in the radiation-oncology ward at Shohada-e-Tajrish Hospital in Tehran, Iran, between 2006 and 2013. They received one of four regimens, i.e., cisplatin, cisplatin with 5-FU (old chemotherapy regimens), cisplatin with paclitaxel, or cisplatin with irinotecan (new chemotherapy regimens) as part of their definitive chemo-radiation with curative intent. The Kaplan-Meier estimator was used to estimate the overall survival times, which were compared by using the Breslow test. Results The follow-up period was between 26–109 months, with a median of 72 months. OS was not different between the old and new chemotherapy regimen groups (p = 0.18). Hematological toxicity (leucopenia) in the old chemotherapy regimen groups (10%) was significantly lower than in the new chemotherapy regimen groups (43%, p = 0.012). But OS in cisplatin or cisplatin with 5-FU scheme was statistically better than with the cisplatin with paclitaxel scheme (p = 0.026, p = 0.028, respectively). Conclusion This study showed that OS are similar in both the old and new chemotherapy treatment regimens in esophageal cancer patients who were treated with definitive chemo-radiation. The new chemotherapy treatment regimens should be used with caution as an alternative

  1. A phase II prospective study of the "Sandwich" protocol, L-asparaginase, cisplatin, dexamethasone and etoposide chemotherapy combined with concurrent radiation and cisplatin, in newly diagnosed, I/II stage, nasal type, extranodal natural killer/T-cell lymphoma.

    PubMed

    Jiang, Ming; Zhang, Li; Xie, Li; Zhang, Hong; Jiang, Yu; Liu, Wei-Ping; Zhang, Wen-Yan; Tian, Rong; Deng, Yao-Tiao; Zhao, Sha; Zou, Li-Qun

    2017-03-17

    Nasal-type, extranodal NK/T cell lymphoma (ENKTCL) is a special type of lymphomas with geographic and racial specificity. Up to now, the standard first-line treatment is still not unified. In our previous report, the "sandwich" protocol produced good results. Continuing to use the "sandwich" mode, a new chemotherapy composed of L-asparaginase, cisplatin, etoposide and dexamethasone (LVDP) plus concurrent chemoradiotherapy (CCRT) was conducted in more patients with newly diagnosed, I/II stage ENKTCL. The results showed that 66 patients were enrolled. Overall response rate was 86.4% including 83.3% complete response and 3.0% partial remission. With the median follow-up of 23.5 months, 3-year overall survival and 3-year progression-free survival were 70.1% and 67.4%, respectively. The survival rate in stage II and extra-cavity stage I was significantly less than that in limited stage I (p < 0.05). Therefore, we thought that the "sandwich" mode was worthy of being generalized and LVDP combined with CCRT was an effective protocol for I/II stage ENKTCL. But this regimen was not suitable for all stage I/II patients and warrants larger sample and layering investigation. This study was a registered clinical trial with number ChiCTR-TNC-12002353.

  2. TET1 promotes cisplatin-resistance via demethylating the vimentin promoter in ovarian cancer.

    PubMed

    Han, Xi; Zhou, Yuanyuan; You, Yuanyi; Lu, Jiaojiao; Wang, Lijie; Hou, Huilian; Li, Jing; Chen, Wei; Zhao, Le; Li, Xu

    2017-04-01

    The development of chemo-resistance impairs the outcome of the first line platinum-based chemotherapies for ovarian cancer. Deregulation of DNA methylation/demethylation provides a critical mechanism for the occurrence of chemo-resistance. The ten-eleven translocation (TET) family of dioxygenases including TET1/2/3 plays an important part in DNA demethylation, but their roles in cisplatin resistance have not been elucidated. Using cisplatin-sensitive and cisplatin-resistant ovarian cancer cell models, we found that TET1 was significantly upregulated in cisplatin-resistant CP70 cells compared with that in cisplatin-sensitive A2780 cells. Ectopic expression of TET1 in A2780 cells promoted cisplatin resistance and decreased cytotoxicity induced by cisplatin, while inhibition of TET1 by siRNA transfection in CP70 cells attenuated cisplatin resistance and enhanced cytotoxicity of cisplatin. Increased TET1 induced re-expression of vimentin through active DNA demethylation, and cause partial epithelial-to-mesenchymal (EMT) in A2780 cells. Contrarily, knocking down of TET1 in CP70 cells reduced vimentin expression and reversed EMT process. Immunohistochemical analysis of TET1 in human ovarian cancer tissues revealed that TET1 existed in nucleus and cytoplasm in ovarian cancer tissues. And the expression of nuclear TET1 was positively correlated with residual tumor and chemotherapeutic response. Thus, TET1 expression causes resistance to cisplatin and one of the targets of TET1 action is vimentin in ovarian cancer.

  3. Reversible p53 inhibition prevents cisplatin ototoxicity without blocking chemotherapeutic efficacy.

    PubMed

    Benkafadar, Nesrine; Menardo, Julien; Bourien, Jérôme; Nouvian, Régis; François, Florence; Decaudin, Didier; Maiorano, Domenico; Puel, Jean-Luc; Wang, Jing

    2017-01-01

    Cisplatin is a widely used chemotherapy drug, despite its significant ototoxic side effects. To date, the mechanism of cisplatin-induced ototoxicity remains unclear, and hearing preservation during cisplatin-based chemotherapy in patients is lacking. We found activation of the ATM-Chk2-p53 pathway to be a major determinant of cisplatin ototoxicity. However, prevention of cisplatin-induced ototoxicity is hampered by opposite effects of ATM activation upon sensory hair cells: promoting both outer hair cell death and inner hair cell survival. Encouragingly, however, genetic or pharmacological ablation of p53 substantially attenuated cochlear cell apoptosis, thus preserving hearing. Importantly, systemic administration of a p53 inhibitor in mice bearing patient-derived triple-negative breast cancer protected auditory function, without compromising the anti-tumor efficacy of cisplatin. Altogether, these findings highlight a novel and effective strategy for hearing protection in cisplatin-based chemotherapy. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

  4. A phase II study of capecitabine and cisplatin (XP) as first-line chemotherapy in patients with advanced esophageal squamous cell carcinoma.

    PubMed

    Lee, Jeeyun; Im, Young-Hyuck; Cho, Eun Yoon; Hong, Yong Sang; Lee, Hyo Rak; Kim, Hyo Song; Kim, Mi-Jin; Kim, Kwhanmien; Kang, Won Ki; Park, Keunchil; Shim, Young Mog

    2008-06-01

    The combination of 5-fluorouracil (5-FU) and cisplatin (FP) remains the mostly used regimen for metastatic esophageal squamous carcinoma. This phase II study assessed the efficacy and safety of capecitabine/cisplatin (XP) as a first-line chemotherapy in a homogenous cohort of patients with metastatic or recurrent esophageal squamous cell carcinoma. Patients received 60 mg/m(2) of cisplatin intravenously (IV) on day 1 and capecitabine 1,250 mg/m(2)/dose orally twice a day on days 1-14. Treatment cycles were repeated every 3 weeks until the documented disease progression, unacceptable toxicity, or patient's refusal. Immunohistochemical studies against thymidylate synthase (TS) and thymidine phosphorylase (TP) were performed to seek predictive markers for treatment response. Between December 2003 and March 2006, 45 patients entered the study. All patients had histologically proven squamous cell carcinoma of the esophagus. The overall response rate (ORR) was 57.8% (95% CI, 43.3-72.2) with 0 CR and 26 PRs. The median duration of response in responders was 4.6 months (1.0-15.6 months). With a median follow-up duration of 25.7 months (10.8-42.6 months), the median time to progression was 4.7 months (95% CI, 2.5-7.0) and the median survival time was 11.2 months (95% CI, 8.5-13.9). Common grade 3 or 4 non-hematological adverse events were anorexia (18/191, 9.4%), fatigue (9/191, 4.7%), constipation (6/191, 3.1%), hand-foot syndrome (6/191, 3.1%) and diarrhea (4/191, 2.1%). The most common grade 3 or 4 hematological adverse events were neutropenia (33/191, 17.3%), followed by leucopenia (11/191, 5.8%), anemia (2/191, 1.0%) and thrombocytopenia (1/191, 0.5%). There was no treatment-related death. Neither TS nor TP showed predictive value for treatment response. The XP regimen demonstrated a promising antitumor activity in metastatic esophageal squamous cell carcinoma, which may potentially replace the FP regimen.

  5. Salvage chemotherapy of gemcitabine, dexamethasone, and cisplatin (GDP) for patients with relapsed or refractory peripheral T-cell lymphomas: a consortium for improving survival of lymphoma (CISL) trial.

    PubMed

    Park, Byeong-Bae; Kim, Won Seog; Suh, Cheolwon; Shin, Dong-Yeop; Kim, Jeong-A; Kim, Hoon-Gu; Lee, Won Sik

    2015-11-01

    There is no standard salvage chemotherapy for relapsed or refractory peripheral T-cell lymphomas (PTCLs). Gemcitabine combined with cisplatin has been known as an effective regimen for lymphoma treatment in the salvage setting. We investigated the efficacy and toxicity of gemcitabine, dexamethasone, and cisplatin (GDP) for relapsed or refractory PTCLs in search of a more effective and less toxic therapy. Patients with relapsed or refractory PTCLs with more than one previous regimen were eligible. Treatment consisted of gemcitabine 1000 mg/m(2) intravenously (i.v.) on days 1 and 8, dexamethasone 40 mg orally on days 1-4, and cisplatin 70 mg/m(2) i.v. on day 1, and then every 21 days. Patients could proceed to autologous stem cell transplantation (ASCT) after four cycles of GDP or receive up to six treatment cycles. Twenty-five eligible patients were evaluated for toxicity and response. The diagnoses of participants included 14 cases of PTCL-not otherwise specified (NOS) (56 %) and four cases of angioimmunoblastic T-cell lymphoma (16 %) among others. The median age of the patients was 59 years (range 20-75 years). After treatments with GDP, which delivered a median of four GDP cycles, there were 12 patients with complete responses (CR; 48 %) and six with partial responses (PR; 24 %). The overall response rate (RR) was 72 %. Four patients preceded to ASCT, and three patients finally achieved CR. The median progression free survival was 9.3 months (95 % confidence interval (CI); 4.1-14.6) with a median follow-up duration of 27.1 months. In a total of 86 cycles of GDP, grade 3 or 4 neutropenia and thrombocytopenia occurred in 16.3 and 12.8 % of cycles, respectively. Three patients (3.3 %) experienced febrile neutropenia. GDP is a highly effective and optimal salvage regimen for relapsed or refractory PTCLs and can be administered with acceptable toxicity.

  6. Ethoxyquin provides neuroprotection against cisplatin-induced neurotoxicity

    PubMed Central

    Zhu, Jing; Carozzi, Valentina Alda; Reed, Nicole; Mi, Ruifa; Marmiroli, Paola; Cavaletti, Guido; Hoke, Ahmet

    2016-01-01

    Ethoxyquin was recently identified as a neuroprotective compound against toxic neuropathies and efficacy was demonstrated against paclitaxel-induced neurotoxicity in vivo. In this study we examined the efficacy of ethoxyquin in preventing neurotoxicity of cisplatin in rodent models of chemotherapy-induced peripheral neuropathy and explored its mechanism of action. Ethoxyquin prevented neurotoxicity of cisplatin in vitro in a sensory neuronal cell line and primary rat dorsal root ganglion neurons. In vivo, chronic co-administration of ethoxyquin partially abrogated cisplatin-induced behavioral, electrophysiological and morphological abnormalities. Furthermore, ethoxyquin did not interfere with cisplatin’s ability to induce tumor cell death in ovarian cancer cell line in vitro and in vivo. Finally, ethoxyquin reduced the levels of two client proteins (SF3B2 and ataxin-2) of a chaperone protein, heat shock protein 90 (Hsp90) when co-administered with cisplatin in vitro. These results implied that the neuroprotective effect of ethoxyquin is mediated through these two client proteins of Hsp90. In fact, reducing levels of SF3B2 in tissue-cultured neurons was effective against neurotoxicity of cisplatin. These findings suggest that ethoxyquin or other compounds that inhibit chaperone activity of Hsp90 and reduce levels of its client protein, SF3B2 may be developed as an adjuvant therapy to prevent neurotoxicity in cisplatin-based chemotherapy protocols. PMID:27350330

  7. Efficacy and safety of single-dose fosaprepitant in the prevention of chemotherapy-induced nausea and vomiting in patients receiving high-dose cisplatin: a multicentre, randomised, double-blind, placebo-controlled phase 3 trial

    PubMed Central

    Saito, H.; Yoshizawa, H.; Yoshimori, K.; Katakami, N.; Katsumata, N.; Kawahara, M.; Eguchi, K.

    2013-01-01

    Background We evaluated the efficacy and safety of single-dose fosaprepitant in combination with intravenous granisetron and dexamethasone. Patients and methods Patients receiving chemotherapy including cisplatin (≥70 mg/m2) were eligible. A total of 347 patients (21% had received cisplatin with vomiting) were enrolled in this trial to receive the fosaprepitant regimen (fosaprepitant 150 mg, intravenous, on day 1 in combination with granisetron, 40 μg/kg, intravenous, on day 1 and dexamethasone, intravenous, on days 1–3) or the control regimen (placebo plus intravenous granisetron and dexamethasone). The primary end point was the percentage of patients who had a complete response (no emesis and no rescue therapy) over the entire treatment course (0–120 h). Results The percentage of patients with a complete response was significantly higher in the fosaprepitant group than in the control group (64% versus 47%, P = 0.0015). The fosaprepitant regimen was more effective than the control regimen in both the acute (0–24 h postchemotherapy) phase (94% versus 81%, P = 0.0006) and the delayed (24–120 h postchemotherapy) phase (65% versus 49%, P = 0.0025). Conclusions Single-dose fosaprepitant used in combination with granisetron and dexamethasone was well-tolerated and effective in preventing chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic cancer chemotherapy, including high-dose cisplatin. PMID:23117073

  8. Surgical outcome after docetaxel-based neoadjuvant chemotherapy in locally-advanced gastric cancer

    PubMed Central

    Biffi, Roberto; Fazio, Nicola; Luca, Fabrizio; Chiappa, Antonio; Andreoni, Bruno; Zampino, Maria Giulia; Roth, Arnaud; Schuller, Jan Christian; Fiori, Giancarla; Orsi, Franco; Bonomo, Guido; Crosta, Cristiano; Huber, Olivier

    2010-01-01

    AIM: To investigate feasibility, morbidity and surgical mortality of a docetaxel-based chemotherapy regimen randomly administered before or after gastrectomy in patients suffering from locally-advanced resectable gastric cancer. METHODS: Patients suffering from locally-advanced (T3-4 any N M0 or any T N1-3 M0) gastric carcinoma, staged with endoscopic ultrasound, bone scan, computed tomography, and laparoscopy, were assigned to receive four 21 d/cycles of TCF (docetaxel 75 mg/m2 day 1, cisplatin 75 mg/m2 day 1, and fluorouracil 300 mg/m2 per day for days 1-14), either before (Arm A) or after (Arm B) gastrectomy. Operative morbidity, overall mortality, and severe adverse events were compared by intention-to-treat analysis. RESULTS: From November 1999 to November 2005, 70 patients were treated. After preoperative TCF (Arm A), thirty-two (94%) resections were performed, 85% of which were R0. Pathological response was complete in 4 patients (11.7%), and partial in 18 (55%). No surgical mortality and 28.5% morbidity rate were observed, similar to those of immediate surgery arm (P = 0.86). Serious chemotherapy adverse events tended to be more frequent in arm B (23% vs 11%, P = 0.07), with a single death per arm. CONCLUSION: Surgery following docetaxel-based chemotherapy was safe and with similar morbidity to immediate surgery in patients with locally-advanced resectable gastric carcinoma. PMID:20143466

  9. Optimising antiemesis in cancer chemotherapy: efficacy of continuous versus intermittent infusion of high dose metoclopramide in emesis induced by cisplatin.

    PubMed Central

    Warrington, P S; Allan, S G; Cornbleet, M A; MacPherson, J S; Smyth, J F; Leonard, R C

    1986-01-01

    Thirty three untreated patients being given cisplatin received metoclopramide (7 mg/kg) for antiemesis by either continuous or intermittent infusion in a random order. Each patient received intravenous dexamethasone in addition. High pressure liquid chromatography was used to measure plasma concentrations of metoclopramide. The two regimens were evaluated for antiemetic efficacy and the incidence of side effects. The intermittent metoclopramide regimen resulted in peak and trough plasma concentrations of metoclopramide with accumulation at eight hours, while the loading dose and continuous infusion resulted in mean plasma concentrations greater than 0.85 micrograms/ml (2.8 mumol/l) throughout the eight hour period. The continuous infusion was associated with a significant improvement in nausea and vomiting and reduction in diarrhoea. Major control of emesis (two episodes or fewer) was achieved in 27 patients receiving continuous metoclopramide compared with 18 receiving intermittent metoclopramide. PMID:3790968

  10. HeLa cell tumor response to 60Co, Cs-137, Cf-252 radiations and cisplatin chemotherapy in nude mice.

    PubMed

    Maruyama, Y; Feola, J M; Beach, J L

    1984-07-15

    HeLa cells were implanted into athymic nude mice from tissue culture and solid tumors established (HeLa cell tumor or HCT). Large cell numbers of 1 X 10(7) were required to obtain consistent and progressive growth, and tumor growth followed a Gompertzian mode. Irradiation studies were carried out using acute Cobalt-60 (60Co), low-dose-rate (LDR) Cs-137 and LDR Cf-252. Cf-252, a neutron-emitting radioisotope, produced an immediate tumor shrinkage and regression response after a dose of 279 cGy. Acute 60Co or LDR Cs-137 irradiation with 1000 cGy had little effect on the HCT. After a dose of 2000 cGy of 60Co radiation tumor shrinkage followed a latent period of approximately 5 days. Cisplatin had no effect on the HCT in nude mice in stationary or late exponential growth.

  11. HeLa cell tumor response to 60Co, Cs-137, Cf-252 radiations and cisplatin chemotherapy in nude mice

    SciTech Connect

    Maruyama, Y.; Feola, J.M.; Beach, J.L.

    1984-07-15

    HeLa cells were implanted into athymic nude mice from tissue culture and solid tumors established (HeLa cell tumor or HCT). Large cell numbers of 1 X 10/sup 7/ were required to obtain consistent and progressive growth, and tumor growth followed a Gompertzian mode. Irradiation studies were carried out using acute Cobalt-60 (60Co), low-dose-rate (LDR) Cs-137 and LDR Cf-252. Cf-252, a neutron-emitting radioisotope, produced an immediate tumor shrinkage and regression response after a dose of 279 cGy. Acute 60Co or LDR Cs-137 irradiation with 1000 cGy had little effect on the HCT. After a dose of 2000 cGy of 60Co radiation tumor shrinkage followed a latent period of approximately 5 days. Cisplatin had no effect on the HCT in nude mice in stationary or late exponential growth.

  12. Long-term Results of a Multicenter Randomized Phase III Trial of Induction Chemotherapy With Cisplatin, 5-fluorouracil, ± Docetaxel for Larynx Preservation.

    PubMed

    Janoray, Guillaume; Pointreau, Yoann; Garaud, Pascal; Chapet, Sophie; Alfonsi, Marc; Sire, Christian; Jadaud, Eric; Calais, Gilles

    2016-04-01

    The purpose of GORTEC 2000-01 was to compare the long-term efficacy and safety of induction chemotherapy with cisplatin (P) and 5-fluorouracil (F) with or without docetaxel (T) for larynx preservation. Operable patients with untreated stage III or IV larynx or hypopharynx invasive squamous cell carcinoma who required total laryngectomy were randomly assigned to three cycles of induction chemotherapy with either TPF or PF, followed by radiation therapy for responders. The primary endpoint was three-year larynx preservation rate. Secondary endpoints included larynx dysfunction-free survival (LDFFS), overall survival (OS), disease-free survival (DFS), loco-regional control rate (LCR), cause of death, and later toxicity rates. Survival and other data were analyzed by Kaplan-Meier methods. All statistical tests were two-sided. Two hundred thirteen patients were treated with median follow-up of 105 months. The five- and 10-year larynx preservation rates were 74.0% (95% CI = 0.64 to 0.82) vs 58.1% (95% CI = 0.47 to 0.68) and 70.3% (95% CI = 0.58 to 0.8) vs 46.5% (95% CI = 0.31 to 0.63, P = .01) in the TPF vs PF arm, respectively. The five- and 10-year LDFFS rates were 67.2% (95% CI = 0.57 to 0.76) vs 46.5% (95% CI = 0.36 to 0.57) and 63.7% (95% CI = 0.52 to 0.74) vs 37.2% (95% CI = 0.24 to 0.52, P = .001), respectively. OS, DFS, and LCR were not statistically improved in the TPF vs the PF arm. Statistically fewer grade 3-4 late toxicities of the larynx occurred with the TPF regimen compared with the PF arm (9.3% vs 17.1%, G-test, P = .038). Long-term follow-up confirms that induction chemotherapy with TPF increased larynx preservation and larynx dysfunction-free survival. In this larynx preservation approach using induction chemotherapy, TPF should be recommended, followed by radiation therapy. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Practical use of perioperative chemotherapy for muscle-invasive bladder cancer: summary of session at the Society of Urologic Oncology annual meeting.

    PubMed

    Apolo, Andrea B; Grossman, Herbert Barton; Bajorin, Dean; Steinberg, Gary; Kamat, Ashish M

    2012-01-01

    At the 11th annual meeting of the Society of Urologic Oncology, an expert panel was convened to discuss the practical use of perioperative chemotherapy for muscle-invasive bladder cancer. The discussion was structured as a case-based debate among the panelists. The topics included: neoadjuvant chemotherapy with a focus on T2 disease, pros and cons, survival data, tolerability of cisplatin-based therapy, can we avoid radical cystectomy in complete responders, limitations and alternatives to cisplatin-based therapy, management of 'suboptimal' chemotherapy, residual disease after neoadjuvant chemotherapy, adjuvant chemotherapy, and key aspects of radical cystectomy and lymph-node dissection in multimodal therapy. The presentations were derived from published literature. The panelists agreed that patients with muscle-invasive bladder cancer should be managed with a multidisciplinary team, including urologist and medical oncologist. Cisplatin-based neoadjuvant chemotherapy has demonstrated improved survival and should be incorporated into the management of all eligible patients with muscle-invasive bladder cancer. However, in some centers, neoadjuvant chemotherapy is reserved for patients with >T2 disease or high-risk features. There are no data for the administration of non-cisplatin-based neoadjuvant chemotherapy, such as carboplatin-combinations. Cisplatin-ineligible patients should proceed directly to surgical extirpation with adjuvant cisplatin-based chemotherapy considered based on pathologic findings. However, the data for adjuvant chemotherapy is less compelling. As our refinement of the selection process continues, we may be able to better identify subsets of patients who may be spared chemotherapy, but much work remains to be done in this arena. The current standard for muscle-invasive bladder cancer patients is cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy and pelvic lymph-node dissection.

  14. Practical Use of Perioperative Chemotherapy for Muscle-Invasive Bladder Cancer: Summary of Session at the Society of Urologic Oncology Annual Meeting

    PubMed Central

    Apolo, Andrea B.; Grossman, H. Barton; Bajorin, Dean; Steinberg, Gary; Kamat, Ashish M.

    2012-01-01

    At the 11th annual meeting of the Society of Urologic Oncology, an expert panel was convened to discuss the practical use of perioperative chemotherapy for muscle-invasive bladder cancer. The discussion was structured as a case-based debate among the panelist. The topics included: neoadjuvant chemotherapy with a focus on T2 disease, pros and cons, survival data, tolerability of cisplatin-based therapy, can we avoid radical cystectomy in complete responders, limitations and alternatives to cisplatin-based therapy, management of ‘suboptimal’ chemotherapy, residual disease after neoadjuvant chemotherapy, adjuvant chemotherapy and key aspects of radical cystectomy and lymph-node dissection in multi-modal therapy. The presentations were derived from published literature. The panelists agreed that patients with muscle-invasive bladder cancer should be managed with a multidisciplinary team including urologist and medical oncologist. Cisplatin-based neoadjuvant chemotherapy has demonstrated improved survival and should be incorporated into the management of all eligible patients with muscle-invasive bladder cancer. However, in some centers neoadjuvant chemotherapy is reserved for patients with >T2 disease or high-risk features. There are no data for the administration of non-cisplatin based neoadjuvant chemotherapy such as carboplatin-combinations. Cisplatin-ineligible patients should proceed directly to surgical extirpation with adjuvant cisplatin-based chemotherapy considered based on pathologic findings. However, the data for adjuvant chemotherapy is less compelling. As our refinement of the selection process continues we may be able to better identify subsets of patients who may be spared chemotherapy, but much work remains to be done in this arena. The current standard for muscle-invasive bladder cancer patients is cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy and pelvic lymph-node dissection. PMID:23218068

  15. An East Asian subgroup analysis of PROCLAIM, a phase III trial of pemetrexed and cisplatin or etoposide and cisplatin plus thoracic radiation therapy followed by consolidation chemotherapy in locally advanced nonsquamous non-small cell lung cancer.

    PubMed

    Wang, Luhua; Wu, Yi-Long; Lu, Shun; Deng, Lei; Ahn, Myung-Ju; Hsu, Feng-Ming; Iscoe, Neill; Hossain, Anwar; Puri, Tarun; Zhang, Pinghai; Orlando, Mauro

    2016-12-01

    PROCLAIM, a phase III trial of patients with nonsquamous non-small cell lung cancer comparing concurrent pemetrexed-cisplatin and thoracic radiation therapy followed by consolidation pemetrexed, did not meet its primary endpoint of superior overall survival versus etoposide-cisplatin and thoracic radiation therapy followed by a consolidation platinum doublet of choice. The results from an East Asian subgroup analysis are presented here. A subgroup analysis was performed for all patients randomized from China (n = 61), Taiwan (n = 25), and Korea (n = 11). Baseline characteristics were balanced between treatment arms for East Asian patients. In the 97 randomized East Asian patients, median overall survival was 26.8 months for the pemetrexed-cisplatin arm and 36.3 months for the etoposide-cisplatin arm (hazard ratio: 1.23; 95% confidence interval: 0.70-2.14; P = 0.469). Median progression-free survival was 10.0 months for the pemetrexed-cisplatin arm and 7.6 months for the etoposide-cisplatin arm (hazard ratio: 0.97; 95% confidence interval: 0.61-1.54; P = 0.890). The objective response rate was 47.7% in the pemetrexed-cisplatin arm and 34.0% in the etoposide-cisplatin arm (P = 0.167). In the 90 treated East Asian patients, the overall incidence of drug-related grade 3-4 treatment-emergent adverse events was significantly lower in the pemetrexed-cisplatin arm versus the etoposide-cisplatin arm (61.4% vs 91.3%; P = 0.001). For East Asian patients, pemetrexed-cisplatin combined with thoracic radiation therapy, followed by consolidation pemetrexed, did not improve overall survival but did have a good safety profile with a trend for improved progression-free survival and objective response rate compared to standard chemoradiotherapy for stage III unresectable nonsquamous non-small cell lung cancer. © 2016 John Wiley & Sons Australia, Ltd.

  16. Cyclosporine A, alpha-lnterferon and interleukin-2 following chemotherapy with BCNU, DTIC, cisplatin, and tamoxifen: a phase II study in advanced melanoma.

    PubMed

    Feun, Lynn; Marini, Angela; Moffat, Frederick; Savaraj, Niramol; Hurley, Judith; Mazumder, Amitabha

    2005-01-01

    Preclinical data suggest that one method of inducing autoimmunity to tumor is the administration and subsequent withdrawal of cyclosporine A following chemotherapy and that this effect may be enhanced with interferon and interleukin-2. Consequently, we performed a phase II trial in patients with advanced melanoma to explore this approach. Thirty-three patients were treated with BCNU (150 mg/m2 iv every 8 weeks), cisplatin (25 mg/m2 iv days 1-3) every 4 weeks, DTIC (220 mg/m2 iv days 1-3 every 4 weeks) along with tamoxifen (10 mg po BID days 1-4). Cyclosporine A at 3 mg/kg/day in two divided doses was given on days 4-21, alpha-interferon 1 million units/m2 subcutaneously every other day on days 4-21 and interleukin-2 1 million units/m2 BID subcutaneously days 21-28 were also given. Of the 33 patients, 3 patients (9%) had complete response and 8 patients (24%) had a partial response for a total response rate of 33% (95% confidence interval 18-52%). Median duration of response was 17 months (range 3+ to 24+ months). Six patients continue to show no signs of tumor progression for 3+, 5+, 10+, 24+, 60+, and 72+ months. Toxicity was generally well tolerated and included myelosuppression and fatigue. This regimen is feasible and generally tolerable and has produced an antitumor response rate comparable with inpatient biochemotherapy regimens.

  17. Phase II study of second-line therapy with DTIC, BCNU, cisplatin and tamoxifen (Dartmouth regimen) chemotherapy in patients with malignant melanoma previously treated with dacarbazine

    PubMed Central

    Propper, D J; Braybrooke, J P; Levitt, N C; O'Byrne, K; Christodoulos, K; Han, C; Talbot, D C; Ganesan, T S; Harris, A L

    2000-01-01

    This study assessed response rates to combination dacarbazine (DTIC), BCNU (carmustine), cisplatin and tamoxifen (DBPT) chemotherapy in patients with progressive metastatic melanoma previously treated with DTIC, as an evaluation of DBPT as a second-line regimen, and as an indirect comparison of DBPT with DTIC. Thirty-five consecutive patients received DBPT. The patients were divided into two groups. Group 1 comprised 17 patients with progressive disease (PD) on DTIC + tamoxifen therapy who were switched directly to DBPT. Group 2 comprised 18 patients not immediately switched to DBPT and included patients who had either a partial response (PR; one patient) or developed stable disease (SD; four patients) with DTIC, or received adjuvant DTIC (nine patients). All except four patients had received tamoxifen at the time of initial DTIC treatment. Median times since stopping DTIC were 22 days (range 20–41) and 285 days (range 50–1240) in Groups 1 and 2 respectively. In Group 1, one patient developed SD for 5 months and the remainder had PD. In Group 2, there were two PRs, four patients with SD (4, 5, 6, and 6 months), and 11 with PD. These results indicate that the DBPT regimen is not of value in melanoma primarily refractory to DTIC. There were responses in patients not directly switched from DTIC to DBPT, suggesting combination therapy may be of value in a small subgroup of melanoma patients. © 2000 Cancer Research Campaign PMID:10839287

  18. Phase II study of second-line therapy with DTIC, BCNU, cisplatin and tamoxifen (Dartmouth regimen) chemotherapy in patients with malignant melanoma previously treated with dacarbazine.

    PubMed

    Propper, D J; Braybrooke, J P; Levitt, N C; O'Byrne, K; Christodoulos, K; Han, C; Talbot, D C; Ganesan, T S; Harris, A L

    2000-06-01

    This study assessed response rates to combination dacarbazine (DTIC), BCNU (carmustine), cisplatin and tamoxifen (DBPT) chemotherapy in patients with progressive metastatic melanoma previously treated with DTIC, as an evaluation of DBPT as a second-line regimen, and as an indirect comparison of DBPT with DTIC. Thirty-five consecutive patients received DBPT. The patients were divided into two groups. Group 1 comprised 17 patients with progressive disease (PD) on DTIC + tamoxifen therapy who were switched directly to DBPT. Group 2 comprised 18 patients not immediately switched to DBPT and included patients who had either a partial response (PR; one patient) or developed stable disease (SD; four patients) with DTIC, or received adjuvant DTIC (nine patients). All except four patients had received tamoxifen at the time of initial DTIC treatment. Median times since stopping DTIC were 22 days (range 20-41) and 285 days (range 50-1,240) in Groups 1 and 2 respectively. In Group 1, one patient developed SD for 5 months and the remainder had PD. In Group 2, there were two PRs, four patients with SD (4, 5, 6, and 6 months), and 11 with PD. These results indicate that the DBPT regimen is not of value in melanoma primarily refractory to DTIC. There were responses in patients not directly switched from DTIC to DBPT, suggesting combination therapy may be of value in a small subgroup of melanoma patients.

  19. [Combination of etoposide, cisplatin and ifosfamide (VPH) in the salvage chemotherapy of relapsing or refractory aggressive malignant lymphoma. Study of 51 patients].

    PubMed

    Eghbali, H; Catry-Thomas, I; Soubeyran, P; Bonnel, C; Hoerni, B

    1994-09-01

    Fifty-one patients with non-Hodgkin's lymphoma refractory or relapsing after CHOP-like regimen, underwent a salvage chemotherapy by VPH: etoposide 100 mg/m2/d, D1 to D3, cisplatin 20 mg/m2/d, D1 to D5, ifosfamide 1 g/m2/d D1 to D5, mesna 1.2 g/m2/d D1 to D5, every 4 weeks. Among 46 evaluable patients for efficacy, 21 (45.6%) achieved complete or partial response according to WHO criteria and 25 (54.3%) failed, while five cases (9.8% of all patients) were not evaluable (two initial complete remission before VPH, two early toxic deaths and one confusional syndrome). Thirty-five patients (68.6%) died of lymphoma, three (5.8%) of acute toxicity and 13 (25.5%) are alive: five in complete remission. The toxicity is mainly myelo-suppression, digestive and renal but could be managed as usually. Although the follow-up is short, this regimen appears effective in these circumstances after CHOP failure but it should be used early, before overt chemoresistance. It does not hinder a bone marrow transplantation programme.

  20. Activity of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) with cisplatin and doxorubicin in women with recurrent, platinum-resistant ovarian cancer: preliminary clinical experience.

    PubMed

    Tempfer, Clemens B; Celik, Ilknur; Solass, Wiebke; Buerkle, Bernd; Pabst, Urs G; Zieren, Juergen; Strumberg, Dirk; Reymond, Marc-André

    2014-02-01

    To assess the activity of laparoscopic Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) in women with recurrent, platinum-resistant ovarian cancer. Prospective case series using repeated courses q 28-42 days of PIPAC containing cisplatin 7.5 mg/m(2) and doxorubicin 1.5 mg/m(2) at 12 mmHg and 37°C for 30 min. Objective tumor response was defined as tumor regression on histology and peritoneal carcinomatosis index (PCI) improvement on repeated video-laparoscopy. 34 PIPAC procedures were performed in 18 women, in 8 instances combined with cytoreductive surgery (CRS). Eight women had repeated PIPAC and objective tumor response was observed in 6 (complete remission: 1; partial remission: 2; stable disease: 3). Five adverse events WHO grade ≥ 2 were noted, 3 of them after combined CRS. No perioperative mortality occurred. Median follow-up was 192 days (min. 13-max. 639). Cumulative survival after 400 days was 62% and mean actuarial survival time was 442 days. In a multivariable regression analysis with objective tumor response (yes vs. no) as the dependent variable and PIPAC (1 vs.>1), patient age (<75 vs.≥75 years), serum CA-125 (<1000 vs.>1000 U/mL), and the presence of ascites (yes vs. no) as independent variables, PIPAC independently predicted objective tumor response. PIPAC has activity in women with recurrent, platinum-resistant ovarian cancer and should be investigated in prospective clinical trials. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. A density functional reactivity theory (DFRT) based approach to understand the interaction of cisplatin analogues with protecting agents

    NASA Astrophysics Data System (ADS)

    Sarmah, Amrit; Roy, Ram Kinkar

    2014-12-01

    In the present study some new insights are put into one of the major concern of cisplatin therapy and that is on the reduction of various cytotoxic and nephrotoxic side-effects of cisplatin analogues in cancer treatment. A better understanding of the interaction between different cisplatin analogues with various protecting agents can be achieved from the descriptors generated by density functional reactivity theory based comprehensive decomposition analysis of stabilization energy (Bagaria et al. in Phys Chem Chem Phys 11:8306-8315, 2009) scheme. Taking into account of three types of interactions i.e., of (1) Cisplatin analogues with DNA bases and base pairs (2) Cisplatin analogues with protecting agents and (3) Protecting agents with DNA bases, it is possible to develop a strategy (albeit qualitative) that suggests the best possible combinations of these drugs with protecting agents which can cause reduction in the toxic side-effects of cisplatin therapy. The sample set comprises of 96 pairs of cisplatin analogues and rescue agents and the generated data confirms the predictive power of the adopted strategy.

  2. SUCCINCT: An Open-label, Single-arm, Non-randomised, Phase 2 Trial of Gemcitabine and Cisplatin Chemotherapy in Combination with Sunitinib as First-line Treatment for Patients with Advanced Urothelial Carcinoma

    PubMed Central

    Geldart, Thomas; Chester, John; Casbard, Angela; Crabb, Simon; Elliott, Tony; Protheroe, Andrew; Huddart, Robert A.; Mead, Graham; Barber, Jim; Jones, Robert J.; Smith, Joanna; Cowles, Robert; Evans, Jessica; Griffiths, Gareth

    2015-01-01

    Gemcitabine and cisplatin chemotherapy (GC regimen) represents a standard treatment for advanced urothelial carcinoma. We performed an open-label, single-arm, non-randomised, phase 2 trial evaluating the addition of sunitinib to standard GC chemotherapy (SGC regimen). Overall, 63 treatment-naïve participants were recruited and received up to six 21-d cycles of cisplatin 70 mg/m2 (intravenously [IV], day 1) and gemcitabine 1000 mg/m2 (IV, days 1 and 8) combined with sunitinib 37.5 mg (orally, days 2–15). Following review of toxicity after the first six patients, the sunitinib dose was reduced to 25 mg for all patients. Overall response rate was 64%, with response noted in 37 of 58 patients. At 6 mo, 30 of 58 assessable patients (52%; 90% confidence interval [CI], 40–63%) were progression free. Median overall survival was 12 mo (95% CI, 9–15) and was heavily influenced by Bajorin prognostic group. Grade 3–4 toxicities were predominantly haematologic and limited the deliverability of the triple SGC regimen. The trial did not meet its prespecified primary end point of >60% patients progression free at 6 mo. Cumulative myelosuppression led to treatment delays of gemcitabine and cisplatin and dose reduction and/or withdrawal of sunitinib in the majority of cases. The triple-drug combination was not well tolerated. Phase 3 evaluation of the triple SGC regimen in advanced transitional cell carcinoma is not recommended. Patient summary The addition of sunitinib to standard cisplatin and gemcitabine chemotherapy was poorly tolerated and did not improve outcomes in advanced urothelial carcinoma. Treatment delivery was limited by myelotoxicity. PMID:25465968

  3. The maintenance of cisplatin- and paclitaxel-induced mechanical and cold allodynia is suppressed by cannabinoid CB2 receptor activation and independent of CXCR4 signaling in models of chemotherapy-induced peripheral neuropathy

    PubMed Central

    2012-01-01

    Background Chemotherapeutic agents produce dose-limiting peripheral neuropathy through mechanisms that remain poorly understood. We previously showed that AM1710, a cannabilactone CB2 agonist, produces antinociception without producing central nervous system (CNS)-associated side effects. The present study was conducted to examine the antinociceptive effect of AM1710 in rodent models of neuropathic pain evoked by diverse chemotherapeutic agents (cisplatin and paclitaxel). A secondary objective was to investigate the potential contribution of alpha-chemokine receptor (CXCR4) signaling to both chemotherapy-induced neuropathy and CB2 agonist efficacy. Results AM1710 (0.1, 1 or 5 mg/kg i.p.) suppressed the maintenance of mechanical and cold allodynia in the cisplatin and paclitaxel models. Anti-allodynic effects of AM1710 were blocked by the CB2 antagonist AM630 (3 mg/kg i.p.), but not the CB1 antagonist AM251 (3 mg/kg i.p.), consistent with a CB2-mediated effect. By contrast, blockade of CXCR4 signaling with its receptor antagonist AMD3100 (10 mg/kg i.p.) failed to attenuate mechanical or cold hypersensitivity induced by either cisplatin or paclitaxel. Moreover, blockade of CXCR4 signaling failed to alter the anti-allodynic effects of AM1710 in the paclitaxel model, further suggesting distinct mechanisms of action. Conclusions Our results indicate that activation of cannabinoid CB2 receptors by AM1710 suppresses both mechanical and cold allodynia in two distinct models of chemotherapy-induced neuropathic pain. By contrast, CXCR4 signaling does not contribute to the maintenance of chemotherapy-induced established neuropathy or efficacy of AM1710. Our studies suggest that CB2 receptors represent a promising therapeutic target for the treatment of toxic neuropathies produced by cisplatin and paclitaxel chemotherapeutic agents. PMID:22998838

  4. Antibody-drug conjugates: targeting melanoma with cisplatin encapsulated in protein-cage nanoparticles based on human ferritin

    NASA Astrophysics Data System (ADS)

    Falvo, Elisabetta; Tremante, Elisa; Fraioli, Rocco; Leonetti, Carlo; Zamparelli, Carlotta; Boffi, Alberto; Morea, Veronica; Ceci, Pierpaolo; Giacomini, Patrizio

    2013-11-01

    A novel antibody-drug conjugate (ADC) was synthesized incorporating ferritin-based nanoparticles. An average of three molecules of monoclonal antibody (mAb) Ep1 to the human melanoma-specific antigen CSPG4 were conjugated to a single ferritin cage encapsulating about 50 cisplatin molecules (HFt-Pt-Ep1). The HFt-Pt-Ep1 nanoparticle had an estimated molecular size of about 900 kD and 33 nm, and flow cytometry demonstrated specific binding to a CSPG4+ melanoma cell line, but not to a CSPG4- breast carcinoma cell line. As compared to the cisplatin-containing ferritin nanoparticle alone (HFt-Pt), which inhibited thymidine incorporation more efficiently in breast carcinoma than melanoma cells, the mAb-derivatized HFt-Pt-Ep1 nanoparticle had a 25-fold preference for the latter. A similar preference for melanoma was observed upon systemic intravenous administration of HFt-Pt-Ep1 to nude mice xenotransplanted with pre-established, palpable melanoma and breast carcinoma tumors. Thus, we have been able to determine precise combinations and stoichiometric relationships between mAbs and nanoparticle protein cages, whereby the latter lose their tropism for ubiquitously distributed cellular receptors, and acquire instead remarkably lineage-selective binding. HFt-Pt-Ep1 is therefore an interesting model to improve the therapeutic index of antiblastic therapy in a tumor such as melanoma, which at its advanced stages is totally refractory to mono- and combination-chemotherapy.A novel antibody-drug conjugate (ADC) was synthesized incorporating ferritin-based nanoparticles. An average of three molecules of monoclonal antibody (mAb) Ep1 to the human melanoma-specific antigen CSPG4 were conjugated to a single ferritin cage encapsulating about 50 cisplatin molecules (HFt-Pt-Ep1). The HFt-Pt-Ep1 nanoparticle had an estimated molecular size of about 900 kD and 33 nm, and flow cytometry demonstrated specific binding to a CSPG4+ melanoma cell line, but not to a CSPG4- breast carcinoma cell

  5. Alterations in endocannabinoid tone following chemotherapy-induced peripheral neuropathy: Effects of endocannabinoid deactivation inhibitors targeting fatty-acid amide hydrolase and monoacylglycerol lipase in comparison to reference analgesics following cisplatin treatment

    PubMed Central

    Guindon, Josée; Lai, Yvonne; Takacs, Sara M.; Bradshaw, Heather B.; Hohmann, Andrea G.

    2012-01-01

    SUMMARY Cisplatin, a platinum-derived chemotherapeutic agent, produces mechanical and cold allodynia reminiscent of chemotherapy-induced neuropathy in humans. The endocannabinoid system represents a novel target for analgesic drug development. The endocannabinoid consists of endocannabinoids (e.g. anandamide (AEA) and 2-arachidonoylglycerol (2-AG)), cannabinoid receptors (e.g. CB1 and CB2) and the enzymes controlling endocannabinoid synthesis and degradation. AEA is hydrolyzed by fatty-acid amide hydrolase (FAAH) whereas 2-AG is hydrolyzed primarily by monoacylglycerol lipase (MGL). We compared effects of brain permeant (URB597) and impermeant (URB937) inhibitors of FAAH with an irreversible inhibitor of MGL (JZL184) on cisplatin-evoked behavioral hypersensitivities. Endocannabinoid modulators were compared with agents used clinically to treat neuropathy (i.e. the opioid analgesic morphine, the anticonvulsant gabapentin and the tricyclic antidepressant amitriptyline). Cisplatin produced robust mechanical and cold allodynia but did not alter responsiveness to heat. After neuropathy was fully established, groups received acute intraperitoneal (i.p.) injections of vehicle, amitriptyline (30 mg/kg), gabapentin (100 mg/kg), morphine (6 mg/kg), URB597 (0.1 or 1 mg/kg), URB937 (0.1 or 1 mg/kg) or JZL184 (1, 3 or 8 mg/kg). Pharmacological specificity was assessed by coadministering each endocannabinoid modulator with either a CB1 (AM251 3 mg/kg), CB2 (AM630 3 mg/kg), TRPV1 (AMG9810 3 mg/kg) or TRPA1 (HC030031 8 mg/kg) antagonist. Effects of cisplatin on endocannabinoid levels and transcription of receptors (CB1, CB2, TRPV1, TRPA1) and enzymes (FAAH, MGL) linked to the endocannabinoid system were also assessed. URB597, URB937, JZL184 and morphine reversed cisplatin-evoked mechanical and cold allodynia to pre-cisplatin levels. By contrast, gabapentin only partially reversed the neuropathy while amitriptyline, administered acutely, was ineffective. CB1 or CB2 antagonist

  6. Alterations in endocannabinoid tone following chemotherapy-induced peripheral neuropathy: effects of endocannabinoid deactivation inhibitors targeting fatty-acid amide hydrolase and monoacylglycerol lipase in comparison to reference analgesics following cisplatin treatment.

    PubMed

    Guindon, Josée; Lai, Yvonne; Takacs, Sara M; Bradshaw, Heather B; Hohmann, Andrea G

    2013-01-01

    Cisplatin, a platinum-derived chemotherapeutic agent, produces mechanical and coldallodynia reminiscent of chemotherapy-induced neuropathy in humans. The endocannabinoid system represents a novel target for analgesic drug development. The endocannabinoid signaling system consists of endocannabinoids (e.g. anandamide (AEA) and 2-arachidonoylglycerol (2-AG)), cannabinoid receptors (e.g. CB(1) and CB(2)) and the enzymes controlling endocannabinoid synthesis and degradation. AEA is hydrolyzed by fatty-acid amide hydrolase (FAAH) whereas 2-AG is hydrolyzed primarily by monoacylglycerol lipase (MGL). We compared effects of brain permeant (URB597) and impermeant (URB937) inhibitors of FAAH with an irreversible inhibitor of MGL (JZL184) on cisplatin-evoked behavioral hypersensitivities. Endocannabinoid modulators were compared with agents used clinically to treat neuropathy (i.e. the opioid analgesic morphine, the anticonvulsant gabapentin and the tricyclic antidepressant amitriptyline). Cisplatin produced robust mechanical and cold allodynia but did not alter responsiveness to heat. After neuropathy was fully established, groups received acute intraperitoneal (i.p.) injections of vehicle, amitriptyline (30 mg/kg), gabapentin (100 mg/kg), morphine (6 mg/kg), URB597 (0.1 or 1 mg/kg), URB937 (0.1 or 1 mg/kg) or JZL184 (1, 3 or 8 mg/kg). Pharmacological specificity was assessed by coadministering each endocannabinoid modulator with either a CB(1) (AM251 3 mg/kg), CB(2) (AM630 3 mg/kg), TRPV1 (AMG9810 3 mg/kg) or TRPA1 (HC030031 8 mg/kg) antagonist. Effects of cisplatin on endocannabinoid levels and transcription of receptors (CB(1), CB(2), TRPV1, TRPA1) and enzymes (FAAH, MGL) linked to the endocannabinoid system were also assessed. URB597, URB937, JZL184 and morphine reversed cisplatin-evoked mechanical and cold allodynia to pre-cisplatin levels. By contrast, gabapentin only partially reversed the observed allodynia while amitriptyline, administered acutely, was ineffective

  7. Correlation of Serum Cystatin C with Glomerular Filtration Rate in Patients Receiving Platinum-Based Chemotherapy

    PubMed Central

    Barchiesi, Vittoria; Cerasuolo, Dionigio; Di Paola, Flaviano; Cantile, Monica; Cecere, Sabrina Chiara; Pignata, Sandro; Morabito, Alessandro; Costanzo, Raffaele; Di Maio, Massimo; Perrone, Francesco

    2016-01-01

    Objectives. Serum cystatin C seems to be an accurate marker of glomerular filtration rate (GFR) compared to serum creatinine. The aim of this work was to explore the possibility of using serum cystatin C instead of serum creatinine to early predict renal failure in cancer patients who received platinum based chemotherapy. Design and Methods. Serum creatinine, serum cystatin C concentrations, and GFR were determined simultaneously in 52 cancer patients received carboplatin-based or cisplatin-based chemotherapy. Serum creatinine was assayed on Cobas C6000-Roche, serum cystatin C assay was performed on AIA 360-Tosoh, and GFR was determined in all patients, before the first cycle of chemotherapy and before the subsequent administrations. Results. In the overall series, for the prediction of a fall of GFR < 80 mL/min/1.73 m2, the AUC of the ROC curve for cystatin C was 0,667 and the best threshold was 1.135 mg/L (sensitivity 90.5%, specificity 61.1%). For a GFR fall < 60 mL/min/1.73 m2, the AUC of ROC curve for cystatin C was 74.3% and the best threshold was 1.415 mg/L (sensitivity 66.7%, specificity 73.2%). Conclusions. Baseline cystatin C values were not able to predict renal failure during subsequent treatment. In conclusion, serum cystatin C is not a reliable early marker to efficiently predict renal failure in patients receiving chemotherapy. PMID:28078200

  8. Correlation of Serum Cystatin C with Glomerular Filtration Rate in Patients Receiving Platinum-Based Chemotherapy.

    PubMed

    Cavalcanti, Ernesta; Barchiesi, Vittoria; Cerasuolo, Dionigio; Di Paola, Flaviano; Cantile, Monica; Cecere, Sabrina Chiara; Pignata, Sandro; Morabito, Alessandro; Costanzo, Raffaele; Di Maio, Massimo; Perrone, Francesco

    2016-01-01

    Objectives. Serum cystatin C seems to be an accurate marker of glomerular filtration rate (GFR) compared to serum creatinine. The aim of this work was to explore the possibility of using serum cystatin C instead of serum creatinine to early predict renal failure in cancer patients who received platinum based chemotherapy. Design and Methods. Serum creatinine, serum cystatin C concentrations, and GFR were determined simultaneously in 52 cancer patients received carboplatin-based or cisplatin-based chemotherapy. Serum creatinine was assayed on Cobas C6000-Roche, serum cystatin C assay was performed on AIA 360-Tosoh, and GFR was determined in all patients, before the first cycle of chemotherapy and before the subsequent administrations. Results. In the overall series, for the prediction of a fall of GFR < 80 mL/min/1.73 m(2), the AUC of the ROC curve for cystatin C was 0,667 and the best threshold was 1.135 mg/L (sensitivity 90.5%, specificity 61.1%). For a GFR fall < 60 mL/min/1.73 m(2), the AUC of ROC curve for cystatin C was 74.3% and the best threshold was 1.415 mg/L (sensitivity 66.7%, specificity 73.2%). Conclusions. Baseline cystatin C values were not able to predict renal failure during subsequent treatment. In conclusion, serum cystatin C is not a reliable early marker to efficiently predict renal failure in patients receiving chemotherapy.

  9. Docetaxel, cisplatin and 5-fluorouracil adjuvant chemotherapy following three-field lymph node dissection for stage II/III N1, 2 esophageal cancer.

    PubMed

    Hashiguchi, Tadasuke; Nasu, Motomi; Hashimoto, Takashi; Kuniyasu, Tetsuji; Inoue, Hirohumi; Sakai, Noritaka; Ouchi, Kazutomo; Amano, Takayuki; Isayama, Fuyumi; Tomita, Natsumi; Iwanuma, Yoshimi; Tsurumaru, Masahiko; Kajiyama, Yoshiaki

    2014-09-01

    To determine the efficacy of postoperative adjuvant chemotherapy with docetaxel + cisplatin + 5-fluorouracil (DCF) in lymph node metastasis-positive esophageal cancer, we retrospectively analyzed 139 patients with stage II/III (non-T4) esophageal cancer with lymph node metastasis (1-6 nodes), who did not receive preoperative treatment and underwent three-field lymph node dissection in the Juntendo University Hospital between December, 2004 and December, 2009. The tumors were histologically diagnossed as squamous cell carcinoma. The patients were divided into two groups, a surgery alone group (S group, 88 patients) and a group that received postoperative DCF therapy (DCF group, 51 patients). The disease-free and overall survival were compared between the groups and a multivariate analysis of prognostic factors was performed. The same analysis was performed for cases classified as N1 and N2, according to the TNM classification. There were no significant differences between the S and DCF groups regarding clinicopathological factors other than intramural metastasis and main tumor location. The presence of intramural metastasis, blood vessel invasion and the number of lymph nodes were identified as prognostic factors. The 5-year disease-free and overall survival were 55.8 and 57.3%, respectively, in the S group and 52.8 and 63.0%, respectively, in the DCF group. These differences were not considered to be statistically significant (P=0.789 and 0.479 for disease-free and overall survival, respectively). Although there were no significant differences in disease-free and overall survival between the S and DCF groups in N1 cases, both disease-free and overall survival were found to be better in the DCF group (54.2 and 61.4%, respectively) compared to the S group (29.6 and 28.8%, respectively) in N2 cases (P=0.029 and 0.020 for disease-free and overall survival, respectively). Therefore, postoperative adjuvant chemotherapy with DCF was shown to improve disease-free and

  10. A phase II trial of TIP (paclitaxel, ifosfamide and cisplatin) given as second-line (post-BEP) salvage chemotherapy for patients with metastatic germ cell cancer: a medical research council trial.

    PubMed

    Mead, G M; Cullen, M H; Huddart, R; Harper, P; Rustin, G J S; Cook, P A; Stenning, S P; Mason, M

    2005-07-25

    This phase II trial describes the use of TIP chemotherapy (paclitaxel, ifosfamide and cisplatin) as salvage for patients with metastatic germ cell cancer (GCC) who have failed initial BEP (bleomycin, etoposide and cisplatin) chemotherapy. Patients with first relapse following BEP for metastatic GCC, confirmed by biopsy or sequentially rising markers, received four courses of TIP (paclitaxel 175 mg m(-2) day 1, followed on days 1-5 by ifosfamide 1 g m(-2) intravenously (i.v.) and cisplatin 20 mg2 i.v.) at 3-weekly intervals. The primary outcome measure was response to TIP. In all, 51 patients were registered, of whom 43 were eligible for response assessment. Eight achieved complete remission (CR) and 18 a partial remission with negative markers (PR(-ve)); favourable response rate (FRR = CR + PR(-ve)) 60%, 95% CI (44-75%); survival at 1 year was 70% (56-84%) and failure-free survival 36% (22-50%). In the group of 26 patients meeting the 'good-risk' criteria described by the Memorial Hospital, the FRR was 73% (52-88%) compared with 41% (18-67%) for the 17 'poor-risk' patients. These results are inferior to those previously reported for TIP in a single-centre study when it was given more intensively, at higher dose and with growth factor support. Nonetheless, TIP as described here can cure a substantial proportion of patients.

  11. Cholesterol reduces the sensitivity to platinum-based chemotherapy via upregulating ABCG2 in lung adenocarcinoma.

    PubMed

    Wu, Yufeng; Si, Ruirui; Tang, Hong; He, Zhen; Zhu, Hui; Wang, Lili; Fan, Yingchao; Xia, Suhua; He, Zelai; Wang, Qiming

    2015-02-20

    Inoperable lung adenocarcinoma is currently treated with platinum-based chemotherapy. However, the effectiveness of these chemotherapeutic agents is not the same for all patients. Patients either show quick chemoresistance (QCR) or delayed chemoresistance (DCR), which are defined by 87 and 242 days of progression-free survival (PFS) after initial platinum-based treatment, respectively. We found that QCR patients displayed an elevated level of serum cholesterol and that their tumors showed upregulated ABCG2 expression. We propose that chemoresistance may be attributed to cholesterol-induced ABCG2 expression and hypothesize that blocking ABCG2 may increase the efficacy of platinum-based chemotherapeutic agents. Using the MTT cell viability assay, we observed that cotreatment with ABCG2 blocker Nicardipine and platinum-based drugs Cisplatin, Oxaliplatin or Carboplatin significantly decreased cell viability of tumor cells. Importantly, our results also showed that incubating cells with cholesterol prior to chemotherapy treatment or cotreatment increased cell viability of tumor cells relative to the controls. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Renal Medulla is More Sensitive to Cisplatin than Cortex Revealed by Untargeted Mass Spectrometry-Based Metabolomics in Rats

    PubMed Central

    Zhang, Pei; Chen, Jia-Qing; Huang, Wan-Qiu; Li, Wei; Huang, Yin; Zhang, Zun-Jian; Xu, Feng-Guo

    2017-01-01

    Nephrotoxicity has long been the most severe and life-threatening side-effect of cisplatin, whose anticancer effect is therefore restricted. Previous pathological studies have shown that both renal cortex and medulla could be injured by cisplatin. Our TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling) assay results further uncovered that medulla subjected more severe injury than cortex. In order to depict the underlying metabolic mechanism of spatial difference in response to cisplatin, in the present study, mass spectrometry-based untargeted metabolomics approach was applied to profile renal cortex and medulla metabolites of rat after receiving a single dose of cisplatin (2.5, 5 or 10 mg/kg). Eventually, 53 and 55 differential metabolites in cortex and medulla were screened out, respectively. Random forest, orthogonal partial least squares-discriminant analysis and metabolic cumulative fold change analysis revealed that metabolic changes in medulla were more obviously dose-dependent than those in cortex, which confirmed the conclusion that medulla was more sensitive to cisplatin exposure. Furthermore, 29 intermediates were recognized as the most contributive metabolites for the sensitivity difference. Metabolic pathways interrupted by cisplatin mainly included amino acid, energy, lipid, pyrimidine, purine, and creatine metabolism. Our findings provide new insight into the mechanism study of cisplatin-induced nephrotoxicity. PMID:28300186

  13. Cisplatin Induced Renal Insufficiency Measured by Glomerular Filtration Rate with 99mTc-DTPA and by using Serum Creatinine based Formulae: A Prospective Study

    PubMed Central

    Deswal, Satyawati; Prakash, Chandra; Singh, Dhananjay Kumar

    2016-01-01

    Introduction Cisplatin also known as Cis-Diammine-Dichloroplatinum (CDDP) is a chemotherapeutic alkylating nephrotoxic agent. Thus, it is necessary to know if renal function is normal before starting chemotherapy. Glomerular Filtration Rate (GFR) can be assessed directly by using a radiopharmaceutical (dGFR). Estimated GFR (eGFR) method use, Serum Creatinine (SCR) levels in mathematical formulae such as Cockroft-Gault (CG) and abbreviated. Modified Diet in Renal Disease (aMDRD). The serum creatinine level is a function of GFR but is relatively insensitive for detecting early renal insufficiency. Aim We aimed to correlate the incidence of Renal Insufficiency (RI) before and one month after completion of chemotherapy treatment by various methods. Materials and Methods In this prospective study, we examined 64 patients with locally advanced head neck and uterine cervix cancers, before and one month after chemotherapy treatment with CDDP. Single agent CDDP was used with dose range between 35mg/m2 as concurrent weekly chemotherapy. Results Baseline RI was seen in 9.3% of patients by SCR levels, in 21.8% by the dGFR method, in 43.75% by the GFR-CG method and in 25% by the GFR-aMDRD formula. We considered GFR of <60 ml/min and SCR >1.5mg% as RI. After completion of treatment, the median RI was seen in 12.5% by SCR levels, 34.38% by dGFR method, 53.13% by GFR-CG method and 40.63% by GFR-aMDRD formula. None of the methods of GFR estimation showed statistically significant increase in RI one month after CDDP infusion. Only a weak correlation was seen between dGFR and eGFR based on SCR value (p=0.006). Conclusion Baseline RI was detected in 12% more cases when measured by dGFR as compared with SCR level. However, mathematical formulae overestimated baseline RI as compared to dGFR. One month after completion of treatment with CDDP chemotherapy, RI increased in 10%-15% cases as detected by all the four evaluated methods. There is weak correlation between SCR and dGFR thus

  14. Cardiovascular Disease Mortality After Chemotherapy or Surgery for Testicular Nonseminoma: A Population-Based Study

    PubMed Central

    Fung, Chunkit; Fossa, Sophie D.; Milano, Michael T.; Sahasrabudhe, Deepak M.; Peterson, Derick R.; Travis, Lois B.

    2015-01-01

    Purpose Increased risks of incident cardiovascular disease (CVD) in patients with testicular cancer (TC) given chemotherapy in European studies were largely restricted to long-term survivors and included patients from the 1960s. Few population-based investigations have quantified CVD mortality during, shortly after, and for two decades after TC diagnosis in the era of cisplatin-based chemotherapy. Patients and Methods Standardized mortality ratios (SMRs) for CVD and absolute excess risks (AERs; number of excess deaths per 10,000 person-years) were calculated for 15,006 patients with testicular nonseminoma reported to the population-based Surveillance, Epidemiology, and End Results program (1980 to 2010) who initially received chemotherapy (n = 6,909) or surgery (n = 8,097) without radiotherapy and accrued 60,065 and 81,227 person-years of follow-up, respectively. Multivariable modeling evaluated effects of age, treatment, extent of disease, and other factors on CVD mortality. Results Significantly increased CVD mortality occurred after chemotherapy (SMR, 1.36; 95% CI, 1.03 to 1.78; n = 54) but not surgery (SMR, 0.81; 95% CI, 0.60 to 1.07; n = 50). Significant excess deaths after chemotherapy were restricted to the first year after TC diagnosis (SMR, 5.31; AER, 13.90; n = 11) and included cerebrovascular disease (SMR, 21.72; AER, 7.43; n = 5) and heart disease (SMR, 3.45; AER, 6.64; n = 6). In multivariable analyses, increased CVD mortality after chemotherapy was confined to the first year after TC diagnosis (hazard ratio, 4.86; 95% CI, 1.25 to 32.08); distant disease (P < .05) and older age at diagnosis (P < .01) were independent risk factors. Conclusion This is the first population-based study, to our knowledge, to quantify short- and long-term CVD mortality after TC diagnosis. The increased short-term risk of CVD deaths should be further explored in analytic studies that enumerate incident events and can serve to develop comprehensive evidence-based approaches

  15. Thalidomide ameliorates cisplatin-induced nephrotoxicity by inhibiting renal inflammation in an experimental model.

    PubMed

    Amirshahrokhi, Keyvan; Khalili, Ali-Reza

    2015-04-01

    Cisplatin is a platinum-based chemotherapy drug. However, its chemotherapeutic use is restricted by serious side effects, especially nephrotoxicity. Inflammatory mechanisms have a significant role in the pathogenesis of cisplatin-induced nephrotoxicity. Thalidomide is an immunomodulatory and anti-inflammatory agent and is used for the treatment of various inflammatory diseases. The purpose of this study was to investigate the potential nephroprotective effect of thalidomide in a mouse model of cisplatin-induced nephrotoxicity. Nephrotoxicity was induced in mice by a single injection of cisplatin (15 mg/kg, i.p.) and treated with thalidomide (50 and 100 mg/kg/day, orally) for 4 days, beginning 24 h prior to the cisplatin injection. Renal toxicity induced by cisplatin was demonstrated by increasing plasma levels of creatinine and blood urea nitrogen (BUN). Cisplatin increased the renal production of the proinflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and transforming growth factor (TGF)-β1. In addition, kidney levels of malondialdehyde (MDA), myeloperoxidase (MPO), and nitric oxide (NO) were increased by cisplatin. Biochemical results showed that thalidomide reduced cisplatin-induced increase in plasma creatinine and BUN. Thalidomide treatment also significantly reduced tissue levels of the proinflammatory cytokines, MDA, MPO, and NO and increased anti-inflammatory cytokine IL-10. Furthermore, histological examination indicated that thalidomide ameliorated renal damage caused by cisplatin. These data suggest that thalidomide attenuates cisplatin-induced nephrotoxicity possibly by inhibition of inflammatory reactions. Taken together, our findings indicate that thalidomide might be a valuable candidate for the prevention of nephrotoxicity in patients receiving cisplatin.

  16. A Phase I/II trial of radiotherapy concurrent with TS-1 plus cisplatin in patients with clinically resectable type 4 or large type 3 gastric cancer: Osaka Gastrointestinal Cancer Chemotherapy Study Group OGSG1205.

    PubMed

    Imano, Motohiro; Furukawa, Hiroshi; Yokokawa, Masaki; Nishimura, Yasumasa; Kurokawa, Yukinori; Satoh, Taroh; Sakai, Daisuke; Yasuda, Takushi; Imamoto, Haruhiko; Tujinaka, Toshimasa; Shimokawa, Toshio; Shiozaki, Hitoshi

    2013-04-01

    A Phase I/II trial of radiotherapy administered concurrently with TS-1 plus cisplatin has been initiated in Japanese patients with clinical resectable type 4 or large type 3 gastric cancer. The aim of this trial is to determine the recommended dose of TS-1 and cisplatin combined with radiotherapy at a fixed dose in the Phase I study, and to evaluate the efficacy and safety in the Phase II study. The primary endpoint for Phase II is the pathological complete response rate, assessed using surgically resected specimens. Secondary endpoints are the response rate, progression-free survival, overall survival, operation transitional rate, R0 resection rate, rate of treatment completion, rate of down-staging and rates of postoperative complications and adverse events. In Phase II, a total of 30 patients will be enrolled in the Osaka Gastrointestinal Cancer Chemotherapy Study Group trial over a period of 6 years.

  17. Survival results of a randomised two-by-two factorial phase II trial comparing neoadjuvant chemotherapy with two and four courses of S-1 plus cisplatin (SC) and paclitaxel plus cisplatin (PC) followed by D2 gastrectomy for resectable advanced gastric cancer.

    PubMed

    Yoshikawa, Takaki; Morita, Satoshi; Tanabe, Kazuaki; Nishikawa, Kazuhiro; Ito, Yuichi; Matsui, Takanori; Fujitani, Kazumasa; Kimura, Yutaka; Fujita, Junya; Aoyama, Toru; Hayashi, Tsutomu; Cho, Haruhiko; Tsuburaya, Akira; Miyashita, Yumi; Sakamoto, Junichi

    2016-07-01

    The prognosis for stage III gastric cancer is unsatisfactory by D2 gastrectomy and S-1 adjuvant chemotherapy. Both S-1 plus cisplatin (SC) and paclitaxel plus cisplatin (PC) are promising regimens as neoadjuvant chemotherapy; however, the optimal duration remains unclear. In this 2×2 randomised phase II trial, stage III gastric cancer patients, those with a prognosis corresponding to stage III, and macroscopically resectable stage IV cases were randomised to two or four courses of S-1 (80 mg/m(2) for 21 d with 1 week rest)/cisplatin (60 mg/m(2) at day 8) or PC (80 and 25 mg/m(2), respectively, on days 1, 8, and 15 with 1 week rest) as neoadjuvant chemotherapy. The primary end-point was the 3-year overall survival (OS). Between October 2009 and July 2011, 83 patients received 2 courses of SC (n=21), 4 courses of SC (n=20), 2 courses of PC (n=21) and 4 courses of PC (n=21). The 3-year OS was 60.9% for SC and 64.3% for PC and 64.3% for the two courses and 61.0% for the four courses. Subset analyses demonstrated no subgroup which showed any potential survival benefit by PC in comparison to SC or by four courses as in comparison to two courses. Two courses of SC as neoadjuvant chemotherapy are recommended as a test arm of a future phase III study for patients with locally advanced gastric cancer. UMIN-000002595. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  18. A phase III trial comparing oral S-1/cisplatin and intravenous 5-fluorouracil/cisplatin in patients with untreated diffuse gastric cancer.

    PubMed

    Ajani, J A; Abramov, M; Bondarenko, I; Shparyk, Y; Gorbunova, V; Hontsa, A; Otchenash, N; Alsina, M; Lazarev, S; Feliu, J; Elme, A; Esko, V; Abdalla, K; Verma, U; Benedetti, F; Aoyama, T; Mizuguchi, H; Makris, L; Rosati, G

    2017-09-01

    The effect of histology-based treatment regimen on diffuse gastric adenocarcinoma has not been evaluated in clinical trials. This international phase III trial evaluated the efficacy and safety of S-1 (a contemporary oral fluoropyrimidine)/cisplatin versus 5-fluorouracil (5-FU)/cisplatin in chemotherapy-naïve patients with diffuse-type adenocarcinoma involving the gastroesophageal junction or stomach. Eligibility criteria included untreated, measurable, advanced diffuse adenocarcinoma confirmed by central pathology and performance status of 0-1. Patients were randomized (2 : 1) to receive S-1/cisplatin or 5-FU/cisplatin. Primary end point was overall survival (OS), and secondary end points were progression-free survival, time to treatment failure, overall response rate, and safety. A multivariable analysis was also carried out. Overall, 361 patients were randomized (S-1/cisplatin, n = 239; 5-FU/cisplatin, n = 122); half (51%) were men, and median age was 56.0 years. In each group, median number of treatment cycles per patient was 4 (range, S-1/cisplatin: 1-20; 5-FU/cisplatin: 1-30), and dose intensity was >95%. OS was not different in the two groups {median OS with S-1/cisplatin, 7.5 [95% confidence interval (CI): 6.7, 9.3]; 5-FU/cisplatin, 6.6 [95% CI: 5.7, 8.1] months; hazard ratio, 0.99 [95% CI: 0.76, 1.28]; P = 0.9312}. Overall response rate was significantly higher in the S-1/cisplatin than 5-FU/cisplatin group (34.7% versus 19.8%; P = 0.01), but progression-free survival and time to treatment failure were not different. Safety was similar between the 2 groups; however, fewer patients treated with S-1/cisplatin than 5-FU/cisplatin had ≥1 grade 3/4 treatment-emergent adverse event or ≥1 adverse event resulting in treatment discontinuation. One treatment-related death occurred in each group. Slow accrual led to early termination. These data suggest that S-1/cisplatin and 5-FU/cisplatin are similar in efficacy and safety in

  19. Complex cisplatin-double strand break (DSB) lesions directly impair cellular non-homologous end-joining (NHEJ) independent of downstream damage response (DDR) pathways.

    PubMed

    Sears, Catherine R; Turchi, John J

    2012-07-13

    The treatment for advanced stage non-small cell lung cancer (NSCLC) often includes platinum-based chemotherapy and IR. Cisplatin and IR combination therapy display schedule and dose-dependent synergy, the mechanism of which is not completely understood. In a series of in vitro and cell culture assays in a NSCLC model, we investigated both the downstream and direct treatment and damage effects of cisplatin on NHEJ catalyzed repair of a DNA DSB. The results demonstrate that extracts prepared from cisplatin-treated cells are fully capable of NHEJ catalyzed repair of a DSB using a non-cisplatin-damaged DNA substrate in vitro. Similarly, using two different host cell reactivation assays, treatment of cells prior to transfection of a linear, undamaged reporter plasmid revealed no reduction in NHEJ compared with untreated cells. In contrast, transfection of a linear GFP-reporter plasmid containing site-specific, cisplatin lesions 6-bp from the termini revealed a significant impairment in DSB repair of the cisplatin-damaged DNA substrates in the absence of cellular treatment with cisplatin. Together, these data demonstrate that impaired NHEJ in combined cisplatin-IR treated cells is likely the result of a direct effect of cisplatin-DNA lesions near a DSB and that the indirect cellular effects of cisplatin treatment are not significant contributors to the synergistic cytotoxicity observed with combination cisplatin-IR treatment.

  20. Reversal of multidrug resistance in human lung cancer cells by delivery of 3-octadecylcarbamoylacrylic acid–cisplatin-based liposomes

    PubMed Central

    Song, Juan; Ren, Weifang; Xu, Tingting; Zhang, Yi; Guo, Hongyu; Zhu, Shanshan; Yang, Li

    2017-01-01

    Liposome-based drug delivery system would be an innovative and promising candidate to circumvent multidrug resistance (MDR) of cisplatin (CDDP). However, the reversal efficacy of liposomal CDDP was severely impaired by weak cellular uptake and insufficient intracellular drug release. In this study, 3-octadecylcarbamoylacrylic acid–CDDP nanocomplex (OMI–CDDP–N)-based liposomes (OCP-L) with high cellular uptake and sufficient intracellular drug release were designed to circumvent MDR of lung cancer. OMI–CDDP–N was synthesized through a pH-sensitive monocarboxylato and an O→Pt coordinate bond, which is more efficient than CDDP. Also, OCP-L incorporated with OMI–CDDP–N could induce effective cellular uptake, enhanced nuclear distribution, and optimal cellular uptake kinetics. In particular, OCP-L presented superior effects on enhancing cell apoptosis and in vitro cytotoxicity in CDDP-resistant human lung cancer (A549/CDDP) cells. The mechanisms of MDR reversal in A549/CDDP cells by OCP-L could attribute to organic cation transporter 2 restoration, ATPase copper-transporting beta polypeptide suppression, hypoxia-inducible factor 1 α-subunit depletion, and phosphatidylinositol 3-kinase/Akt pathway inhibition. These results demonstrated that OCP-L may provide an effective delivery of CDDP to resistant cells to circumvent MDR and enhance the therapeutic index of the chemotherapy. PMID:28255230

  1. Stanniocalcin 2 promotes cell proliferation and cisplatin resistance in cervical cancer

    SciTech Connect

    Wang, Yuxia; Gao, Ying; Cheng, Hairong; Yang, Guichun; Tan, Wenhua

    2015-10-23

    Cervical cancer is one of the most common carcinomas in the female reproductive system. Treatment of cervical cancer involves surgical removal and chemotherapy. Resistance to platinum-based chemotherapy drugs including cisplatin has increasingly become an important problem in the treatment of cervical cancer patients. We found in this study that stanniocalcin 2 (STC2) expression was upregulated in both cervical cancer tissues and cell lines. The levels of STC2 expression in cervical cancer cell lines were positively correlated with the rate of cell proliferation. Furthermore, in cisplatin resistant cervical cancer cells, the levels of STC2 expression were significantly elevated. Modulation of STC2 expression by siRNA or overexpression in cisplatin resistant cells resulted in altered cell survival, apoptosis, and cisplatin resistance. Finally, we found that there was significant difference in the activity of the MAPK signaling pathway between cisplatin sensitive and resistant cervical cancer cells, and that STC2 could regulate the activity of the MAPK signaling pathway. - Highlights: • STC2 was upregulated in cervical cancer and promoted cervical cancer cell proliferation. • Cisplatin resistant cells had elevated STC2 levels and enhanced proliferation. • STC2 regulated cisplatin chemosensitivity in cervical cancer cells. • STC2 regulated the activity of the MAPK signaling pathway.

  2. Cisplatin Injection

    MedlinePlus

    ... has worsened after treatment with other medications or radiation therapy. Cisplatin is used alone or in combination ... has worsened after treatment with other medications or radiation therapy. Cisplatin is also used alone or in ...

  3. Tumour- and treatment-related colostomy rates following mitomycin C or cisplatin chemoradiation with or without maintenance chemotherapy in squamous cell carcinoma of the anus in the ACT II trial.

    PubMed

    Glynne-Jones, R; Kadalayil, L; Meadows, H M; Cunningham, D; Samuel, L; Geh, J I; Lowdell, C; James, R; Beare, S; Begum, R; Ledermann, J A; Sebag-Montefiore, D

    2014-08-01

    Squamous cell carcinoma of the anus (SCCA) is highly sensitive to chemoradiation (CRT) which achieves good loco-regional control and preserves anal function. However, some patients require permanent stoma formation either as a result of surgery on relapse, poor anal function or treatment-related symptoms. Our aim was to determine patient, tumour and treatment-related colostomy rates following CRT and maintenance chemotherapy in the ACT II trial. The ACT II trial recruited 940 patients comparing 5FU-based CRT using cisplatin (CisP) or mitomycin C (MMC) with or without additional maintenance chemotherapy. We investigated the association between colostomy-free survival (CFS) and progression-free survival (PFS) with age, gender, T-stage, N-stage, treatment and baseline haemoglobin. The median follow-up was 5.1 years (n = 884 evaluable/940); tumour site canal (84%), margin (14%); stage T1/T2 (52%), T3/T4 (46%); N+ (32%), N0 (62%). Twenty out of 118 (17%) colostomies fashioned before CRT were reversed within 8 months. One hundred and twelve patients had a post-treatment colostomy due to persistent disease (98) or morbidity (14). Fifty-two per cent (61/118) of all pre-treatment colostomies were never reversed. The 5-year CFS rates were 68% MMC/Maint, 70% CisP/Maint, 68% MMC/No-maint and 65% CisP/No-maint. CRT with CisP did not improve CFS when compared with MMC (hazard ratio: 1.04, 95% confidence interval: 0.82-1.31, P = 0.74). The 5-year CFS rates were higher for T1/T2 (79%) than T3/T4 (54%) tumours and higher for node-negative (72%) than node-positive (60%) patients. Significant predictors of CFS were gender, T-stage and haemoglobin, while treatment factors had no impact on outcome. Similar associations were found between PFS and tumour/treatment-related factors. The majority (52%) of pre-treatment colostomies were never reversed. Neither CRT with 5FU/CisP nor maintenance chemotherapy impacted on CFS. The low risk of colostomy for late effects (1.7%) is likely to be

  4. A 2-DE-based proteomic study on the toxicological effects of cisplatin in L02 cells.

    PubMed

    Liu, Shu; Wang, Wei; Zhou, Xueyi; Ding, Zongli; Gu, Runhuan

    2015-01-01

    Cisplatin is a chemotherapeutic agent for the treatment of various cancers. In this study, cisplatin-induced effects were characterized in vitro model of human liver cells (L02) using 2-DE-based proteomics. Results indicated that different cisplatin treatments primarily induced disturbances in protein synthesis and oxidative stress via differential mechanisms. Since the experimental concentrations of cisplatin described a hormesis effect in cell proliferation of L02 cells, it was expected to reveal the hormesis effects using proteomic markers. However, only confilin-1 was commonly up-regulated in three concentrations of cisplatin treatments showing a hormesis effects with a U-shape regulation. These results were highly consistent with many other toxico-proteomic studies, indicating that the toxico-proteomic responses based on dose-dependent protein responses were incongruent with the theoretically linear or hormetic concentration-effect relationship. Our findings suggested that a macroscopic hormesis phenomenon on the cell proliferation could not be reflected by proteomic responses induced by cisplatin treatments.

  5. Cost-effectiveness of continuation maintenance pemetrexed after cisplatin and pemetrexed chemotherapy for advanced nonsquamous non-small-cell lung cancer: estimates from the perspective of the Chinese health care system.

    PubMed

    Zeng, Xiaohui; Peng, Liubao; Li, Jianhe; Chen, Gannong; Tan, Chongqing; Wang, Siying; Wan, Xiaomin; Ouyang, Lihui; Zhao, Ziying

    2013-01-01

    Continuation maintenance treatment with pemetrexed is approved by current clinical guidelines as a category 2A recommendation after induction therapy with cisplatin and pemetrexed chemotherapy (CP strategy) for patients with advanced nonsquamous non-small-cell lung cancer (NSCLC). However, the cost-effectiveness of the treatment remains unclear. We completed a trial-based assessment, from the perspective of the Chinese health care system, of the cost-effectiveness of maintenance pemetrexed treatment after a CP strategy for patients with advanced nonsquamous NSCLC. A Markov model was developed to estimate costs and benefits. It was based on a clinical trial that compared continuation maintenance pemetrexed therapy plus best supportive care (BSC) versus placebo plus BSC after a CP strategy for advanced nonsquamous NSCLC. Sensitivity analyses were conducted to assess the stability of the model. The model base case analysis suggested that continuation maintenance pemetrexed therapy after a CP strategy would increase benefits in a 1-, 2-, 5-, or 10-year time horizon, with incremental costs of $183,589.06, $126,353.16, $124,766.68, and $124,793.12 per quality-adjusted life-year gained, respectively. The most sensitive influential variable in the cost-effectiveness analysis was the utility of the progression-free survival state, followed by proportion of patients with postdiscontinuation therapy in both arms, proportion of BSC costs for PFS versus progressed survival state, and cost of pemetrexed. Probabilistic sensitivity analysis indicated that the cost-effective probability of adding continuation maintenance pemetrexed therapy to BSC was zero. One-way and probabilistic sensitivity analyses revealed that the Markov model was robust. Continuation maintenance of pemetrexed after a CP strategy for patients with advanced nonsquamous NSCLC is not cost-effective based on a recent clinical trial. Decreasing the price or adjusting the dosage of pemetrexed may be a better option

  6. What Is the Most Effective Drug Delivery System for Cisplatin during the Treatment of Hepatic Tumors with Single-Session Transcatheter Chemotherapy? A Pilot Study

    PubMed Central

    Ikeda, Kenji; Fukushima, Taito; Seko, Yuya; Hara, Tasuku; Sezaki, Hitomi; Hosaka, Tetsuya; Akuta, Norio; Kobayashi, Masahiro; Saitoh, Satoshi; Suzuki, Fumitaka; Suzuki, Yoshiyuki; Arase, Yasuji; Kumada, Hiromitsu

    2013-01-01

    Background/Aims The aim of this study was to determine the pharmacodynamics of cisplatin following three different treatment procedures for intrahepatic arterial infusion therapy for hepatocellular carcinoma (HCC). Methods We divided 13 HCC patients into the following three groups: group A, lone injection of cisplatin (n=3); group B, combined injection of cisplatin and lipiodol, with embolization using small gelatin cubes (GCs) (n=5); and group C, injection of suspended lipiodol with cisplatin powder, with embolization using small GCs (n=5). In each group, the free cisplatin concentration in the hepatic vein was measured at 0, 5, 10, and 30 minutes. Results The mean free cisplatin concentrations were as follows. For group A, the mean was 48.58 µg/mL at 0 minute, 7.31 µg/mL at 5 minutes, 5.70 µg/mL at 10 minutes, and 7.15 µg/mL at 30 minutes. For the same time points, for group B, the concentrations were 8.66, 4.23, 3.22, and 1.65 µg/mL, respectively, and for group C, the concentrations were 4.81, 2.61, 2.52, and 1.75 µg/mL, respectively. The mean area under the curve (AUC)0-infinity for the free cisplatin concentration was 7.80 in group A, 2.48 in group B, and 2.27 in group C. The AUC0-infinity for the free cisplatin concentration gradually decreased, from group A to group C. Conclusions These results indicate that the combination of lipiodol and small GCs may be useful for delaying cisplatin drainage from the liver. PMID:24073316

  7. Phase II study of induction chemotherapy with gemcitabine and vinorelbine followed by concurrent chemoradiotherapy with oral etoposide and cisplatin in patients with inoperable stage III non-small-cell lung cancer

    SciTech Connect

    Lee, Dae Ho; Han, Ji-Youn; Cho, Kwan Ho; Pyo, Hong Ryull; Kim, Hyae Young; Yoon, Sung Jin B.S.; Lee, Jin Soo . E-mail: jslee@ncc.re.kr

    2005-11-15

    Purpose: For locoregionally advanced inoperable non-small-cell lung cancer (NSCLC), concurrent chemoradiotherapy has become a standard therapy. We conducted a Phase II trial to examine the efficacy and toxicity of adding gemcitabine and vinorelbine induction chemotherapy to concurrent chemoradiotherapy with oral etoposide and cisplatin. Methods and Materials: Eligibility included inoperable clinical Stage III NSCLC without pleural effusion, ECOG performance status 0-1, and weight loss {<=}5%. Induction chemotherapy consisted of three cycles of gemcitabine 1,000 mg/m{sup 2} and vinorelbine 30 mg/m{sup 2}, each given i.v. on Days 1 and 8, every 3 weeks. During once-daily thoracic radiotherapy (1.8 Gy/day, total 63 Gy), two cycles of oral etoposide (100 mg on Days 1-5 and 8-12) plus cisplatin (50 mg/m{sup 2} on Days 1 and 8) were given concurrently 4 weeks apart. Results: Between April 2002 and November 2003, 42 patients were enrolled and 40 were included in response and toxicity evaluation. The median age was 59 years and 13 patients had IIIA and 27 had IIIB; 24 had squamous ca, 12 had adenocarcinoma, and 4 had others. Objective tumor responses were obtained in 29 patients (72.5%), including 18 (45.0%) after induction chemotherapy. After a median follow-up of 23.8 months, the median survival time and progression-free survival was 23.2 months and 10.9 months, respectively, with 2-year survival rate of 43.9%. For the patients with supraclavicular nodal involvement, the median survival time was 11.8 months with 2-year survival rate of 16.7%, whereas the corresponding figures were 27.8 months and 52.0%, respectively, for those without supraclavicular nodal involvement. Toxicity of induction chemotherapy was mild and well tolerated. However, concurrent chemoradiotherapy was associated with G3/4 hematologic toxicity in 75.7%, G3 esophagitis in 24.2%, and two treatment-related deaths. There were nonlife-threatening late toxicities in additional 6 patients. Conclusions

  8. Systemic cisplatin exposure during infancy and adolescence causes impaired cognitive function in adulthood.

    PubMed

    John, Tami; Lomeli, Naomi; Bota, Daniela A

    2017-02-15

    Cancer survivors diagnosed during infancy and adolescence may be at risk for chemotherapy-related cognitive impairments (CRCI), however the effects of pediatric chemotherapy treatment on adulthood cognitive function are not well understood. Impairments in memory, attention and executive function affect 15-50% of childhood leukemia survivors related to methotrexate exposure. Systemic cisplatin is used to treat a variety of childhood and adult cancers, yet the risk and extent of cognitive impairment due to platinum-based chemotherapy in pediatric patients is unknown. Systemic cisplatin penetrates the CNS, induces hippocampal synaptic damage, and leads to neuronal and neural stem/progenitor cell (NSC) loss. Survivors of non-leukemic cancers may be at risk for significant cognitive impairment related to cisplatin-driven neurotoxicity. We sought to examine the long-term effects of systemic cisplatin administration on cognitive function when administered during infancy and adolescence in a rat model. We performed cognitive testing in adult rats exposed to systemic cisplatin during either infancy or adolescence. Rats treated as adolescents showed significantly poor retrieval of a novel object as compared to controls. Further, cisplatin-treated infants and adolescents showed poor contextual discrimination as compared to controls, and an impaired response to cued fear conditioning. Ultimately, systemic cisplatin exposure resulted in more profound impairments in cognitive function in rats treated during adolescence than in those treated during infancy. Further, exposure to cisplatin during adolescence affected both hippocampus and amygdala dependent cognitive function, suggesting a more global cognitive dysfunction at this age. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. The effects of miR-1207-5p expression in peripheral blood on cisplatin-based chemosensitivity of primary gallbladder carcinoma

    PubMed Central

    Shen, Er-Dong; Liu, Bo; Yu, Xin-Shuang; Xiang, Zhen-Fei; Huang, Hui-Yun

    2016-01-01

    Objective The aim of this study was to investigate the association between miR-1207-5p expression in peripheral blood and the chemosensitivity of primary gallbladder carcinoma (PGBC). Methods A total of 85 patients with PGBC undergoing preoperative chemotherapy were divided into effective (n=18) and ineffective (n=67) groups. Another 70 healthy individuals were selected as the control group. An miR-1207-5p mimic (mimic group), an inhibitor (inhibitor group), and a negative control (NC group) sequence were transfected into human gallbladder carcinoma GBC-SD cells. Real-time quantitative polymerase chain reaction was used to determine miR-1207-5p expression. After 48 hours of cisplatin treatment, CCK-8 method was used to detect cell proliferation and flow cytometry were performed to examine cell apoptosis. Results miR-1207-5p expression in peripheral blood was significantly associated with tumor node metastasis staging of PGBC (P<0.05). Before chemotherapy, miR-1207-5p expression in patients was higher than in healthy individuals (P<0.05). After chemotherapy, the effective group had lower miR-1207-5p expression than the ineffective group (P<0.05). The rates of positive expression of Ki67 protein in the effective group were significantly lower than those in the ineffective group (P<0.05). Receiver operating characteristic curves showed that the area under curve, sensitivity, and specificity of miR-1207-5p used to diagnose PGBC were 0.898, 77.6%, and 97.1% at a cutoff of 1.470, respectively. After 48 hours of cisplatin treatment, compared with the NC group and nontransfected (non-T) group, the mimic group had decreased rates of cell inhibition and apoptosis, but the inhibitor group had increased rates (all P<0.05). The expression levels of caspase3 protein were increased in the mimic group and decreased in the inhibitor group. Cell survival rates in the mimic group at different time points after cisplatin treatment were significantly higher than the corresponding rates

  10. RTOG 0417: Efficacy of Bevacizumab in Combination With Definitive Radiation Therapy and Cisplatin Chemotherapy in Untreated Patients With Locally Advanced Cervical Carcinoma

    SciTech Connect

    Schefter, Tracey; Winter, Kathryn; Kwon, Janice S.; Stuhr, Kelly; Balaraj, Khalid; Yaremko, Brian Patrick; Small, William; Sause, William; Gaffney, David

    2014-01-01

    Purpose: Radiation Therapy Oncology Group 0417 was a phase II study that explored the safety and efficacy of the addition of bevacizumab to chemoradiation therapy. The safety results have been previously reported. Herein we report the secondary efficacy endpoints of overall survival (OS), locoregional failure (LRF), para-aortic nodal failure (PAF), distant failure (DF), and disease-free survival (DFS). Methods and Materials: Eligible patients with bulky Stage IB-IIIB disease were treated with once-weekly cisplatin (40 mg/m{sup 2}) chemotherapy and standard pelvic radiation therapy and brachytherapy. Bevacizumab was administered at 10 mg/kg intravenously every 2 weeks for 3 cycles during chemoradiation. For OS, failure was defined as death of any cause and was measured from study entry to date of death. LRF was defined as any failure in the pelvis. PAF was defined as any para-aortic nodal failure. DF was analyzed both including and excluding PAF. DFS was measured from study entry to date of first LRF. DF was measured with or without PAF or death. OS and DFS were estimated by the Kaplan-Meier method, and LRF and DF rates were estimated by the cumulative incidence method. Results: 49 eligible patients from 28 institutions were enrolled between 2006 and 2009. The median follow-up time was 3.8 years (range, 0.8-6.0 years). The surviving patients had a median follow-up time of 3.9 years (range, 2.1-6.0 years). Most patients had tumors of International Federation of Gynecology and Obstetrics Stage IIB (63%), and 80% were squamous. The 3-year OS, DFS, and LRF were 81.3% (95% confidence interval [CI], 67.2%-89.8%), 68.7% (95% CI, 53.5%-79.8%), and 23.2% (95% CI, 11%-35.4%), respectively. The PAF, DF without PAF, and DF with PAF at 3 years were 8.4% (95% CI, 0.4%-16.3%), 14.7% (95% CI, 4.5%-24.9%), and 23.1% (95% CI 11.0%-35.2%), respectively. Conclusion: In this study, bevacizumab in combination with standard pelvic chemoradiation therapy for locally advanced cervical

  11. Feasibility of concurrent chemoradiotherapy with high-dose cisplatin after induction TPF chemotherapy in head and neck cancer: a critical review of the literature and the experience of the European Institute of Oncology.

    PubMed

    Alterio, D; Cossu Rocca, M; Russell-Edu, W; Dicuonzo, S; Fanetti, G; Marvaso, G; Preda, L; Zorzi, S; Verri, E; Nole', F; Jereczek-Fossa, B A

    2017-05-01

    Many concerns are related to the idea that the acute toxicity of induction chemotherapy (IC) performed with TPF (docetaxel, cisplatin, 5-fluorouracil) could reduce the ability to deliver the subsequent standard concurrent chemoradiotherapy (CRT) in head and neck cancer patients. We performed a critical review of the literature on the toxicity profile of the standard CRT administered after the IC with TPF. A total of 13 papers (including 950 patients) were selected. Results showed that most patients were treated with an adequate radiation total dose although a significant proportion of them (from 15 to 30%) completed the planned treatment with a delay of more than 5 days. A minority of patients were able to be treated with three cycles of concurrent cisplatin, but only few papers reported how many of patients reached the cumulative total dose of almost 200 mg/m(2) cisplatin. The rate of deaths due to treatment-related toxicity varied from 0 to 9% (median and mean 2%). Two prospective trials stopped patient enrollment due to acute treatment-related toxicity and because a low number of patients were able to undergo the planned full schedule of cisplatin during the CRT, respectively. Retrospective analysis of 45 patients treated at our institute showed that this schedule was feasible with manageable side effects. In conclusion, the literature data did not provide homogeneous information on the feasibility of the standard CRT after induction TPF. A more uniform data collection of treatment-related toxicity will be helpful in better selecting the patients who might adequately tolerate this multimodality strategy.

  12. Additive effect of rikkunshito, an herbal medicine, on chemotherapy-induced nausea, vomiting, and anorexia in uterine cervical or corpus cancer patients treated with cisplatin and paclitaxel: results of a randomized phase II study (JORTC KMP-02)

    PubMed Central

    Ohba, Yoko; Miyaji, Tempei; Nomura, Eiji; Sugiyama, Toru; Asaka, Masahiro

    2017-01-01

    Objective Rikkunshito, an herbal medicine, is widely prescribed in Japan for the treatment of anorexia and functional dyspepsia, and has been reported to recover reductions in food intake caused by cisplatin. We investigated whether rikkunshito could improve chemotherapy-induced nausea and vomiting (CINV) and anorexia in patients treated with cisplatin. Methods Patients with uterine cervical or corpus cancer who were to receive cisplatin (50 mg/m2 day 1) and paclitaxel (135 mg/m2 day 0) as first-line chemotherapy were randomly assigned to the rikkunshito group receiving oral administration on days 0–13 with standard antiemetics, or the control group receiving antiemetics only. The primary endpoint was the rate of complete control (CC: no emesis, no rescue medication, and no significant nausea) in the overall phase (0–120 hours). Two-tailed p<0.20 was considered significant in the planned analysis. Results The CC rate in the overall phase was significantly higher in the rikkunshito group than in the control group (57.9% vs. 35.3%, p=0.175), as were the secondary endpoints: the CC rate in the delayed phase (24–120 hours), and the complete response (CR) rates (no emesis and no rescue medication) in the overall and delayed phases (63.2% vs. 35.3%, p=0.095; 84.2% vs. 52.9%, p=0.042; 84.2% vs. 52.9%, p=0.042, respectively), and time to treatment failure (p=0.059). Appetite assessed by visual analogue scale (VAS) appeared to be superior in the rikkunshito group from day 2 through day 6. Conclusion Rikkunshito provided additive effect for the prevention of CINV and anorexia. PMID:28657216

  13. Urinary neutrophil gelatinase-associated lipocalin levels predict cisplatin-induced acute kidney injury better than albuminuria or urinary cystatin C levels.

    PubMed

    Lin, Hugo You-Hsien; Lee, Su-Chu; Lin, Sheng-Fung; Hsiao, Hui-Hua; Liu, Yi-Chang; Yang, Wen-Chi; Hwang, Daw-Yang; Hung, Chi-Chih; Chen, Hung-Chun; Guh, Jinn-Yuh

    2013-06-01

    Cisplatin-induced acute kidney injury (AKI) is a major concern among clinicians in prescribing cisplatin-based chemotherapy. This study evaluated and compared the ability of urinary biomarkers, including urinary neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, and the urinary albumin to creatinine ratio (ACR) to predict cisplatin-induced AKI. Thirty-three cancer patients receiving cisplatin-based chemotherapy were prospectively studied, including 10 (30%) who developed AKI (the study group). Changes of urinary biomarkers were compared at 4 hours, 8 hours, and 12 hours, and 1 day, 2 days, 3 days, and 4 days after cisplatin intravenous infusions (75mg/m(2)) versus the baseline. There was a significant increase in urinary NGAL levels from 12 hours to 4 days (p<0.05) compared to baseline after cisplatin infusion in the AKI group. The magnitude of these changes over time differed significantly by group (p<0.001). The area under the receiver operating curve describing the relationship between urinary NGAL levels and AKI within 12 hours was 0.865 (95% confidence interval=0.691-1.000). Urinary NGAL levels independently predicted AKI 12 hours after cisplatin (p=0.045) after adjustments for age, gender, body mass index, baseline serum creatinine, and urinary total protein. Urinary NGAL levels may be an early biomarker of AKI in patients receiving cisplatin-based treatment.

  14. Paclitaxel plus cisplatin vs. 5-fluorouracil plus cisplatin as first-line treatment for patients with advanced squamous cell esophageal cancer.

    PubMed

    Liu, Ying; Ren, Zhonghai; Yuan, Long; Xu, Shuning; Yao, Zhihua; Qiao, Lei; Li, Ke

    2016-01-01

    Paclitaxel plus cisplatin and 5-fluorouracil plus cisplatin treatments are effective strategies for patients with advanced esophageal squamous cell carcinoma. This study was to evaluate the safety and efficacy of paclitaxel plus cisplatin and 5-fluorouracil plus cisplatin as first-line chemotherapy for patients with advanced esophageal squamous cell carcinoma. A total of 398 patients with advanced esophageal squamous cell carcinoma who received chemotherapy were included and divided into 2 groups: paclitaxel plus cisplatin group and 5-fluorouracil plus cisplatin group. 195 patients received paclitaxel plus cisplatin and 203 patients received 5-fluorouracil plus cisplatin. The objective response rates were 42.5% and 38.4% for paclitaxel plus cisplatin group and 5-fluorouracil plus cisplatin group, respectively (P=0.948). The median progression-free survival was 7.85 months (95% CI, 6.77-8.94 months) for the paclitaxel plus cisplatin group and 6.53 months (95% CI, 5.63-7.43 months) for the 5-fluorouracil plus cisplatin group with significant difference (P=0.02). The median overall survival was 13.46 months (95% CI, 12.01-14.91 months) for the paclitaxel plus cisplatin group and 12.67 months (95% CI, 11.87-13.47 months) for the 5-fluorouracil plus cisplatin group (P=0.204). The first-line chemotherapy of paclitaxel plus cisplatin had better median progression-free survival than 5-fluorouracil plus cisplatin in patients with advanced esophageal squamous cell carcinoma with tolerable toxicities.

  15. Empirical force field for cisplatin based on quantum dynamics data: case study of new parameterization scheme for coordination compounds.

    PubMed

    Yesylevskyy, S; Cardey, Bruno; Kraszewski, S; Foley, Sarah; Enescu, Mironel; da Silva, Antônio M; Dos Santos, Hélio F; Ramseyer, Christophe

    2015-10-01

    Parameterization of molecular complexes containing a metallic compound, such as cisplatin, is challenging due to the unconventional coordination nature of the bonds which involve platinum atoms. In this work, we develop a new methodology of parameterization for such compounds based on quantum dynamics (QD) calculations. We show that the coordination bonds and angles are more flexible than in normal covalent compounds. The influence of explicit solvent is also shown to be crucial to determine the flexibility of cisplatin in quantum dynamics simulations. Two empirical topologies of cisplatin were produced by fitting its atomic fluctuations against QD in vacuum and QD with explicit first solvation shell of water molecules respectively. A third topology built in a standard way from the static optimized structure was used for comparison. The later one leads to an excessively rigid molecule and exhibits much smaller fluctuations of the bonds and angles than QD reveals. It is shown that accounting for the high flexibility of cisplatin molecule is needed for adequate description of its first hydration shell. MD simulations with flexible QD-based topology also reveal a significant decrease of the barrier of passive diffusion of cisplatin accross the model lipid bilayer. These results confirm that flexibility of organometallic compounds is an important feature to be considered in classical molecular dynamics topologies. Proposed methodology based on QD simulations provides a systematic way of building such topologies.

  16. Gemcitabine-Based Combination Chemotherapy Followed by Radiation With Capecitabine as Adjuvant Therapy for Resected Pancreas Cancer

    SciTech Connect

    Desai, Sameer; Ben-Josef, Edgar; Griffith, Kent A.; Simeone, Diane; Greenson, Joel K.; Francis, Isaac R.; Hampton, Janet; Colletti, Lisa; Chang, Alfred E.; Lawrence, Theodore S.; Zalupski, Mark M.

    2009-12-01

    Purpose: To report outcomes for patients with resected pancreas cancer treated with an adjuvant regimen consisting of gemcitabine-based combination chemotherapy followed by capecitabine and radiation. Patients and Methods: We performed a retrospective review of a series of patients treated at a single institution with a common postoperative adjuvant program. Between January 2002 and August 2006, 43 resected pancreas cancer patients were offered treatment consisting of 4, 21-day cycles of gemcitabine 1 g/m{sup 2} intravenously over 30 min on Days 1 and 8, with either cisplatin 35 mg/m{sup 2} intravenously on Days 1 and 8 or capecitabine 1500 mg/m{sup 2} orally in divided doses on Days 1-14. After completion of combination chemotherapy, patients received a course of radiotherapy (54 Gy) with concurrent capecitabine (1330 mg/m{sup 2} orally in divided doses) day 1 to treatment completion. Results: Forty-one patients were treated. Median progression-free survival for the entire group was 21.7 months (95% confidence interval 13.9-34.5 months), and median overall survival was 45.9 months. In multivariate analysis a postoperative CA 19-9 level of >=180 U/mL predicted relapse and death. Toxicity was mild, with only two hospitalizations during adjuvant therapy. Conclusions: A postoperative adjuvant program using combination chemotherapy with gemcitabine and either cisplatin or capecitabine followed by radiotherapy with capecitabine is tolerable and efficacious and should be considered for Phase III testing in this group of patients.

  17. Paclitaxel and platinum-based chemotherapy results in transient dyslipidemia in cancer patients

    PubMed Central

    Wang, Guoping; Su, Chao; Yin, Tao

    2017-01-01

    Paclitaxel and cisplatin (TP) are common chemotherapeutic agents extensively used for treating lung and esophageal cancers. The present study reported three patients with transient hypertriglyceridemia (HTG) following TP chemotherapy. Serum triglyceride (TG) levels returned to baseline at chemotherapy intermission. No patient had any history of HTG or any evidence of pancreatitis or other complications of HTG. No regular elevation of any other serum lipids, including cholesterol, high-density lipoprotein and low-density lipoprotein, was observed. However, treatment of mice with TP decreased TG and slightly increased cholesterol. The findings of the present study suggested that TP chemotherapy results in transient dyslipidemia, and physicians must monitor TG levels during chemotherapy to avoid TG-associated complications. PMID:28357107

  18. Selective activation of SHP2 activity by cisplatin revealed by a novel chemical probe-based assay

    SciTech Connect

    Kuo, Chun-Chen; Chu, Chi-Yuan; Lin, Jing-Jer; Lo, Lee-Chiang

    2010-01-01

    Src homology-2 (SH2) domain-containing phosphatase 2 (SHP2) is known to participate in several different signaling pathways to mediate cell growth, survival, migration, and differentiation. However, due to the lack of proper analytical tools, it is unclear whether the phosphatase activity of SHP2 is activated in most studies. We have previously developed an activity-based probe LCL2 that formed covalent linkage with catalytically active protein tyrosine phosphatases (PTPs). Here, by combining LCL2 with a SHP2 specific antibody, we established an assay system that enables the direct monitoring of SHP2 activity upon cisplatin treatment of cancer cells. The protocol is advantageous over conventional colorimetric or in-gel PTP assays as it is specific and does not require the use of radioisotope reagents. Using this assay, we found SHP2 activity was selectively activated by cisplatin. Moreover, the activation of SHP2 appeared to be specific for cisplatin as other DNA damage agents failed to activate the activity. Although the role of SHP2 activation by cisplatin treatments is still unclear to us, our results provide the first direct evidence for the activation of SHP2 during cisplatin treatments. More importantly, the concept of using activity-based probe in conjunction with target-specific antibodies could be extended to other enzyme classes.

  19. Cisplatin-induced downregulation of miR-199a-5p increases drug resistance by activating autophagy in HCC cell

    SciTech Connect

    Xu, Ning; Zhang, Jianjun; Shen, Conghuan; Luo, Yi; Xia, Lei; Xue, Feng; Xia, Qiang

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer miR-199a-5p levels were significantly decreased after cisplatin treatment. Black-Right-Pointing-Pointer Cisplatin treatment induced autophagy activation. Black-Right-Pointing-Pointer Cisplatin-induced downregulation of miR-199a-5p increases drug resistance by activating autophagy in HCC cell. -- Abstract: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Systemic chemotherapy plays an important role in the treatment of patients with advanced liver cancer. However, chemoresistance to cisplatin is a major limitation of cisplatin-based chemotherapy in the clinic, and the underlying mechanism of such resistance is not fully understood. In the study, we found that miR-199a-5p levels were significantly reduced in HCC patients treated with cisplatin-based chemotherapy. Cisplatin treatment also resulted in decreased miR-199a-5p levels in human HCC cell lines. Forced expression of miR-199a-5p promoted cisplatin-induced inhibition of cell proliferation. Cisplatin treatment activated autophagy in Huh7 and HepG2 cells, which increased cell proliferation. We further demonstrated that downregulated miR-199a-5p enhanced autophagy activation by targeting autophagy-associated gene 7 (ATG7). More important, autophagy inhibition abrogated miR-199a-5p downregulation-induced cell proliferation. These data demonstrated that miR-199a-5p/autophagy signaling represents a novel pathway regulating chemoresistance, thus offering a new target for chemotherapy of HCC.

  20. Chemotherapy

    MedlinePlus

    ... able to change the environment around the cell. Hormones—These substances may interfere with tumor growth by blocking the production of certain proteins in the tumor cells. Mitotic inhibitors—These agents are usually plant-based, natural substances that interfere with the production ...

  1. Long-term outcome of patients with clinical stage I high-risk nonseminomatous germ-cell tumors 15 years after one adjuvant cycle of bleomycin, etoposide, and cisplatin chemotherapy.

    PubMed

    Vidal, A D; Thalmann, G N; Karamitopoulou-Diamantis, E; Fey, M F; Studer, U E

    2015-02-01

    To report the long-term results of adjuvant treatment with one cycle of modified bleomycin, etoposide, and cisplatin (BEP) in patients with clinical stage I (CS I) nonseminomatous germ-cell tumors (NSGCT) at high risk of relapse. In a single-arm, phase II clinical trial, 40 patients with CS I NSGCT with vascular invasion and/or >50% embryonal cell carcinoma in the orchiectomy specimen received one cycle of adjuvant BEP (20 mg/m(2) bleomycin as a continuous infusion over 24 h, 120 mg/m(2) etoposide and 40 mg/m(2) cisplatin each on days 1-3). Primary end point was the relapse rate. Median follow-up was 186 months. One patient (2.5%) had a pulmonary relapse 13 months after one BEP and died after three additional cycles of BEP chemotherapy. Three patients (7.5%) presented with a contralateral metachronous testicular tumor, and three (7.5%) developed a secondary malignancy. Three patients (7.5%) reported intermittent tinnitus and one had grade 2 peripheral polyneuropathy (2.5%). Adjuvant chemotherapy with one cycle of modified-BEP is a feasible and safe treatment of patients with CS I NSGCT at high risk of relapse. In these patients, it appears to be an alternative to two cycles of BEP and to have a lower relapse rate than retroperitoneal lymph node dissection. If confirmed by other centers, 1 cycle of adjuvant BEP chemotherapy should become a first-line treatment option for this group of patients. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  2. Similar cisplatin sensitivity of HPV-positive and -negative HNSCC cell lines.

    PubMed

    Busch, Chia-Jung; Becker, Benjamin; Kriegs, Malte; Gatzemeier, Fruzsina; Krüger, Katharina; Möckelmann, Nikolaus; Fritz, Gerhard; Petersen, Cordula; Knecht, Rainald; Rothkamm, Kai; Rieckmann, Thorsten

    2016-06-14

    Patients with HPV-positive head and neck squamous cell carcinoma (HNSCC) show better survival rates than those with HPV-negative HNSCC. While an enhanced radiosensitivity of HPV-positive tumors is clearly evident from single modality treatment, cisplatin is never administered as monotherapy and therefore its contribution to the enhanced cure rates of HPV-positive HNSCC is not known. Both cisplatin and radiotherapy can cause severe irreversible side effects and therefore various clinical studies are currently testing deintensified regimes for patients with HPV-positive HNSCC. One strategy is to omit cisplatin-based chemotherapy or replace it by less toxic treatments but the risk assessment of these approaches remains difficult. In this study we have compared the cytotoxic effects of cisplatin in a panel of HPV-positive and -negative HNSCC cell lines alone and when combined with radiation.While cisplatin-treated HPV-positive strains showed a slightly stronger inhibition of proliferation, there was no difference regarding colony formation. Cellular responses to the drug, namely cell cycle distribution, apoptosis and γH2AX-induction did not differ between the two entities but assessment of cisplatin-DNA-adducts suggests differences regarding the mechanisms that determine cisplatin sensitivity. Combining cisplatin with radiation, we generally observed an additive but only in a minority of strains from both entities a clear synergistic effect on colony formation. In summary, HPV-positive and -negative HNSCC cells were equally sensitive to cisplatin. Therefore replacing cisplatin may be feasible but the substituting agent should be of similar efficacy in order not to jeopardize the high cure rates for HPV-positive HNSCC.

  3. Similar cisplatin sensitivity of HPV-positive and -negative HNSCC cell lines

    PubMed Central

    Kriegs, Malte; Gatzemeier, Fruzsina; Krüger, Katharina; Möckelmann, Nikolaus; Fritz, Gerhard; Petersen, Cordula; Knecht, Rainald; Rothkamm, Kai; Rieckmann, Thorsten

    2016-01-01

    Patients with HPV-positive head and neck squamous cell carcinoma (HNSCC) show better survival rates than those with HPV-negative HNSCC. While an enhanced radiosensitivity of HPV-positive tumors is clearly evident from single modality treatment, cisplatin is never administered as monotherapy and therefore its contribution to the enhanced cure rates of HPV-positive HNSCC is not known. Both cisplatin and radiotherapy can cause severe irreversible side effects and therefore various clinical studies are currently testing deintensified regimes for patients with HPV-positive HNSCC. One strategy is to omit cisplatin-based chemotherapy or replace it by less toxic treatments but the risk assessment of these approaches remains difficult. In this study we have compared the cytotoxic effects of cisplatin in a panel of HPV-positive and -negative HNSCC cell lines alone and when combined with radiation. While cisplatin-treated HPV-positive strains showed a slightly stronger inhibition of proliferation, there was no difference regarding colony formation. Cellular responses to the drug, namely cell cycle distribution, apoptosis and γH2AX-induction did not differ between the two entities but assessment of cisplatin-DNA-adducts suggests differences regarding the mechanisms that determine cisplatin sensitivity. Combining cisplatin with radiation, we generally observed an additive but only in a minority of strains from both entities a clear synergistic effect on colony formation. In summary, HPV-positive and -negative HNSCC cells were equally sensitive to cisplatin. Therefore replacing cisplatin may be feasible but the substituting agent should be of similar efficacy in order not to jeopardize the high cure rates for HPV-positive HNSCC. PMID:27127883

  4. Enhancement of cisplatin efficacy by thalidomide in a 9L rat gliosarcoma model.

    PubMed

    Murphy, Susan; Davey, Ross A; Gu, Xiao-Qing; Haywood, Miriam C; McCann, Lauren A; Mather, Laurence E; Boyle, Frances M

    2007-11-01

    With the aim of improving the treatment of glioblastoma multiforme, we investigated the potential of thalidomide to enhance the effectiveness of cisplatin chemotherapy in a rat glioma model. Female F344 rats were implanted with 9L gliosarcoma tumors either intracranially or subcutaneously and treated with 1 mg/kg cisplatin injected i.p. or with 1% thalidomide in the food or with these treatments combined. Cisplatin in combination with thalidomide significantly reduced both the subcutaneous tumor volume at 30 days to 22 +/- 5% (mean +/- SEM, P < 0.001) and the intracranial tumor volume at 18 days to 44 +/- 15% (P < 0.05) of that with cisplatin alone. Thalidomide selectively increased the cisplatin concentration 10-fold in intracranial tumors (P < 0.05) and 2-fold in the subcutaneous tumors (P < 0.05) without increasing its concentration in major organs including brain and kidney. Cisplatin combined with thalidomide caused a significant decrease in vascular endothelial growth factor (VEGF) levels by 73% in intracranial tumors (P < 0.05) and by 50% in subcutaneous tumors (P < 0.05) and caused the level of active hepatic growth factor (a-HGF) to double in both the subcutaneous and intracranial tumors (P < 0.05), suggesting this treatment altered the vasculature in these tumors. We conclude the increased efficacy of cisplatin in the presence of thalidomide was due to the selective increase in cisplatin concentration within the tumors and speculate that this is the result of thalidomide or the cisplatin/thalidomide combination, selectively altering the tumor vasculature. Based on the selective effects of thalidomide on tumor cisplatin concentrations and the resulting increase in efficacy, thalidomide may also increase the efficacy of other drugs that are presently considered ineffective against glioma.

  5. Discovery – Cisplatin and The Treatment of Testicular and Other Cancers

    Cancer.gov

    Prior to the discovery of cisplatin in 1965, men with testicular cancer had few medical options. Now, thanks to NCI research, cisplatin and similar chemotherapy drugs are known for curing testicular and other forms of cancer.

  6. Involvement of caspase-dependent and -independent apoptotic pathways in cisplatin-induced apoptosis

    NASA Astrophysics Data System (ADS)

    Liu, Lei; Zhang, Yingjie; Wang, Xianwang

    2009-02-01

    Cisplatin, an efficient anticancer agent, can trigger multiple apoptotic pathways in cancer cells. However, the signal transduction pathways in response to cisplatin-based chemotherapy are complicated, and the mechanism is not fully understood. In current study, we showed that, during cisplatin-induced apoptosis of human lung adenocarcinoma cells, both the caspase-dependent and -independent pathways were activated. Herein, we reported that after cisplatin treatment, the activities of caspase-9/-3 were sharply increased; pre-treatment with Z-LEHD-fmk (inhibitor of caspase-9), Z-DEVD-fmk (inhibitor of caspase-3), and Z-VAD-fmk (a pan-caspase inhibitor) increased cell viability and decreased apoptosis, suggesting that caspase-mediated apoptotic pathway was activated following cisplatin treatment. Confocal imaging of the cells transfected with AIF-GFP demonstrated that AIF release occurred about 9 h after cisplatin treatment. The event proceeded progressively over time, coinciding with a nuclear translocation and lasting for more than 2 hours. Down-regulation of AIF by siRNA also significantly increased cell viability and decreased apoptosis, these results suggested that AIF-mediated caspase-independent apoptotic pathway was involved in cispatin-induced apoptosis. In conclusion, the current study demonstrated that both caspase-dependent and -independent apoptotic pathways were involved in cisplatin-induced apoptosis in human lung adenocarcinoma cells.

  7. Targeting drug transport mechanisms for improving platinum-based cancer chemotherapy

    PubMed Central

    Chen, Helen HW; Chen, Wen-Chung; Liang, Zhang-Dong; Tsai, Wen-Bin; Long, Yan; Aiba, Isamu; Fu, Siqing; Broaddus, Russell; Liu, Jinsong; Feun, Lynn G; Savaraj, Niramol; Kuo, Macus Tien

    2016-01-01

    Introduction Platinum (Pt)-based antitumor agents remain important chemotherapeutic agents for treating many human malignancies. Elevated expression of the human high-affinity copper transporter 1 (hCtr1), resulting in enhanced Pt drug transport into cells, has been shown to be associated with improved treatment efficacy. Thus, targeting hCtr1 upregulation is an attractive strategy for improving the treatment efficacy of Pt-based cancer chemotherapy. Area covered Regulation of hCtr1 expression by cellular copper homeostasis is discussed. Association of elevated hCtr1 expression with intrinsic sensitivity of ovarian cancer to Pt drugs is presented. Mechanism of copper-lowering agents in enhancing hCtr1-mediated cis-diamminedichloroplatinum (II) (cisplatin, cDDP) transport is reviewed. Applications of copper chelation strategy in overcoming cDDP resistance through enhanced hCtr1 expression are evaluated. Expert opinion While both transcriptional and posttranslational mechanisms of hCtr1 regulation by cellular copper bioavailability have been proposed, detailed molecular insights into hCtr1 regulation by copper homeostasis remain needed. Recent clinical study using a copper-lowering agent in enhancing hCtr1-mediated drug transport has achieved incremental improvement in overcoming Pt drug resistance. Further improvements in identifying predictive measures in the subpopulation of patients that can benefit from the treatment are needed. PMID:26004625

  8. Mifepristone prevents repopulation of ovarian cancer cells escaping cisplatin-paclitaxel therapy

    PubMed Central

    2012-01-01

    Background Advanced ovarian cancer is treated with cytoreductive surgery and combination platinum- and taxane-based chemotherapy. Although most patients have acute clinical response to this strategy, the disease ultimately recurs. In this work we questioned whether the synthetic steroid mifepristone, which as monotherapy inhibits the growth of ovarian cancer cells, is capable of preventing repopulation of ovarian cancer cells if given after a round of lethal cisplatin-paclitaxel combination treatment. Methods We established an in vitro approach wherein ovarian cancer cells with various sensitivities to cisplatin or paclitaxel were exposed to a round of lethal doses of cisplatin for 1 h plus paclitaxel for 3 h. Thereafter, cells were maintained in media with or without mifepristone, and short- and long-term cytotoxicity was assessed. Results Four days after treatment the lethality of cisplatin-paclitaxel was evidenced by reduced number of cells, increased hypodiploid DNA content, morphological features of apoptosis, DNA fragmentation, and cleavage of caspase-3, and of its downstream substrate PARP. Short-term presence of mifepristone either enhanced or did not modify such acute lethality. Seven days after receiving cisplatin-paclitaxel, cultures showed signs of relapse with escaping colonies that repopulated the plate in a time-dependent manner. Conversely, cultures exposed to cisplatin-paclitaxel followed by mifepristone not only did not display signs of repopulation following initial chemotherapy, but they also had their clonogenic capacity drastically reduced when compared to cells repopulating after cisplatin-paclitaxel. Conclusions Cytostatic concentrations of mifepristone after exposure to lethal doses of cisplatin and paclitaxel in combination blocks repopulation of remnant cells surviving and escaping the cytotoxic drugs. PMID:22642877

  9. Group-Wide, Prospective Study of Ototoxicity Assessment in Children Receiving Cisplatin Chemotherapy (ACCL05C1): A Report From the Children's Oncology Group.

    PubMed

    Knight, Kristin R; Chen, Lu; Freyer, David; Aplenc, Richard; Bancroft, Mary; Bliss, Bonnie; Dang, Ha; Gillmeister, Biljana; Hendershot, Eleanor; Kraemer, Dale F; Lindenfeld, Lanie; Meza, Jane; Neuwelt, Edward A; Pollock, Brad H; Sung, Lillian

    2017-02-01

    Purpose Optimal assessment methods and criteria for reporting hearing outcomes in children who receive treatment with cisplatin are uncertain. The objectives of our study were to compare different ototoxicity classification systems, to evaluate the feasibility of including otoacoustic emissions and extended high frequency audiometry, and to evaluate a central review mechanism for audiologic results for cisplatin-treated children in the cooperative group setting. Patients and Methods Eligible participants were 1 to 30 years, with planned cisplatin-containing treatment. Hearing evaluations were conducted at baseline, before each cisplatin cycle, and at the end of therapy. Audiologic results were assessed and graded by the testing audiologist and by two central review audiologists using the American Speech-Language-Hearing Association Ototoxicity Criteria (ASHA), Common Terminology Criteria for Adverse Events, version 3.0 (CTCAE), and Brock Ototoxicity Grades (Brock). One central reviewer also used the Society for Industrial and Organizational Psychology Ototoxicity Scale (SIOP). Results At the end of treatment, the prevalence of any degree of ototoxicity ranged from 40% to 56%, and severe ototoxicity ranged from 7% to 22%. Compared with CTCAE, SIOP detected significantly more ototoxicity ( P = .004), whereas Brock criteria detected significantly fewer patients with any or severe ototoxicity ( P < .001 for both). SIOP detected ototoxicity earlier than did the other scales. Agreement between the central reviewers and the institutional audiologist was almost perfect for ASHA and Brock, whereas the poorest agreement occurred with CTCAE. Conclusion The SIOP scale may be superior to ASHA, Brock, and CTCAE scales for classifying ototoxicity in pediatric patients who were treated with cisplatin. Future studies should evaluate inter-rater reliability of the SIOP scale.

  10. Platinum-Based Chemotherapy for Variant Castrate-Resistant Prostate Cancer

    PubMed Central

    Aparicio, Ana M.; Harzstark, Andrea L.; Corn, Paul G.; Wen, Sijin; Araujo, John C.; Tu, Shi-Ming; Pagliaro, Lance C.; Kim, Jeri; Millikan, Randall E.; Ryan, Charles J.; Tannir, Nizar M.; Zurita, Amado J.; Mathew, Paul; Arap, Wadih; Troncoso, Patricia; Thall, Peter F.; Logothetis, Christopher J.

    2013-01-01

    Purpose Clinical features characteristic of small-cell prostate carcinoma (SCPC), (““anaplastic””) often emerge during the progression of prostate cancer. We sought to determine the efficacy of platinum-based chemotherapy in patients meeting at least one of seven prospectively defined “anaplastic” clinical criteria, including exclusive visceral or predominantly lytic bone metastases, bulky tumor masses, low PSA levels relative to tumor burden or short response to androgen deprivation therapy. Experimental Design A 120-patient phase II trial of frontline carboplatin and docetaxel (CD) and second-line etoposide and cisplatin (EP) was designed to provide reliable clinical response estimates under a Bayesian probability model with early stopping rules in place for futility and toxicity. Results Seventy-four of 113 (65.4%) and 24 of 71 (33.8%) were progression free after 4 cycles of CD and EP, respectively. Median overall survival (OS) was 16 months (95% CI, 13.6-19.0 months). Of the 7 “anaplastic” criteria, bulky tumor mass was significantly associated with poor outcome. Lactic acid dehydrogenase (LDH) strongly predicted for OS and rapid progression. Serum carcinoembryonic antigen (CEA) concentration strongly predicted OS but not rapid progression. Neuroendocrine markers did not predict outcome or response to therapy. Conclusion Our findings support the hypothesis that patients with “anaplastic” prostate cancer are a recognizable subset characterized by a high response rate of short duration to platinum-containing chemotherapies, similar to SCPC. Our results suggest that CEA is useful for selecting therapy in men with CRPC and consolidative therapies to bulky high-grade tumor masses should be considered in this patient population. PMID:23649003

  11. Chemotherapy for bladder cancer: treatment guidelines for neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and metastatic cancer.

    PubMed

    Sternberg, Cora N; Donat, S Machele; Bellmunt, Joaquim; Millikan, Randall E; Stadler, Walter; De Mulder, Pieter; Sherif, Amir; von der Maase, Hans; Tsukamoto, Taiji; Soloway, Mark S

    2007-01-01

    To determine the optimal use of chemotherapy in the neoadjuvant, adjuvant, and metastatic setting in patients with advanced urothelial cell carcinoma, a consensus conference was convened by the World Health Organization (WHO) and the Société Internationale d'Urologie (SIU) to critically review the published literature on chemotherapy for patients with locally advanced bladder cancer. This article reports the development of international guidelines for the treatment of patients with locally advanced bladder cancer with neoadjuvant and adjuvant chemotherapy. Bladder preservation is also discussed, as is chemotherapy for patients with metastatic urothelial cancer. The conference panel consisted of 10 medical oncologists and urologists from 3 continents who are experts in this field and who reviewed the English-language literature through October 2004. Relevant English-language literature was identified with the use of Medline; additional cited works not detected on the initial search regarding neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and chemotherapy for patients with metastatic urothelial cancer were reviewed. Evidence-based recommendations for diagnosis and management of the disease were made with reference to a 4-point scale. Results of the authors' deliberations are presented as a consensus document. Meta-analysis of randomized trials on cisplatin-containing combination neoadjuvant chemotherapy revealed a 5% difference in favor of neoadjuvant chemotherapy. No randomized trials have yet compared survival with transurethral resection of bladder tumor alone versus cystectomy for the management of patients with muscle-invasive disease. Collaborative international adjuvant chemotherapy trials are needed to assist researchers in assessing the true value of adjuvant chemotherapy. Systemic cisplatin-based combination chemotherapy is the only current modality that has been shown in phase 3 trials to improve survival in responsive patients

  12. Clinical predictor of survival following docetaxel-based chemotherapy

    PubMed Central

    LEE, HSIANG-YING; WU, WEN-JENG; HUANG, CHUN-HSIUNG; CHOU, YII-HER; HUANG, CHUN-NUNG; LEE, YUNG-CHIN; YANG, KAI-FU; LEE, MEI-HUI; HUANG, SHU-PIN

    2014-01-01

    Prostate cancer (PCa) is the most common type of cancer in males in the USA and the incidence is increasing. For castration-resistant PCa (CRPC), previous studies have identified docetaxel-based chemotherapy as the first-line therapy. In the present study, the efficacy of docetaxel-based chemotherapy was investigated in a population of patients with CRPC. This study included 26 individuals (mean age, 73 years) with CRPC who were patients between July 2007 and October 2012 at the Kaohsiung Medical University Hospital (Kaohsiung, Taiwan). The regimen consisted of intravenous docetaxel (70 mg/m2) once every four weeks plus oral prednisolone (5 mg) twice daily for five days. Prostate-specific antigen (PSA) response (defined as a PSA decrease of >50% over four weeks), time to PSA progression, PCa-specific survival and overall survival (OS) were evaluated. For these 26 patients, the mean PSA level prior to chemotherapy treatment was 335.58 ng/ml. During follow-up, the average number of cycles of chemotherapy was approximately seven and 15 patients (58%) achieved a PSA response. PSA response was found to significantly correlate with OS and PCa-specific survival (P=0.014 and P=0.028, respectively). The mean value of the PSA nadir level was 89.97 ng/ml and time to PSA nadir was five months. The most common adverse event was leucopenia, which affected 88% of the patients. The results indicated that the length of time to PSA nadir and the occurrence of leucopenia may impact the PSA response. The docetaxel-based chemotherapy was a feasible and effective treatment regimen in patients with CRPC. However, the occurrence of adverse events, particularly the high incidence of leucopenia, may be cause for concern. PMID:25202411

  13. 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

  14. Multicenter Phase II Study Evaluating Two Cycles of Docetaxel, Cisplatin and Cetuximab as Induction Regimen Prior to Surgery in Chemotherapy-Naive Patients with NSCLC Stage IB-IIIA (INN06-Study)

    PubMed Central

    Hilbe, Wolfgang; Pall, Georg; Kocher, Florian; Pircher, Andreas; Zabernigg, August; Schmid, Thomas; Schumacher, Michael; Jamnig, Herbert; Fiegl, Michael; Gächter, Anne; Freund, Martin; Kendler, Dorota; Manzl, Claudia; Zelger, Bettina; Popper, Helmut; Wöll, Ewald

    2015-01-01

    Background Different strategies for neoadjuvant chemotherapy in patients with early stage NSCLC have already been evaluated. The aim of this study was to evaluate the tolerability and efficacy of a chemoimmunotherapy when limited to two cycles. Methods Between 01/2007 and 03/2010 41 patients with primarily resectable NSCLC stage IB to IIIA were included. Treatment consisted of two cycles cisplatin (40 mg/m2 d1+2) and docetaxel (75 mg/m2 d1) q3 weeks, accompanied by the administration of cetuximab (400 mg/m2 d1, then 250 mg weekly). The primary endpoint was radiological response according to RECIST. Results 40 patients were evaluable for toxicity, 39 for response. The main grade 3/4 toxicities were: neutropenia 25%, leucopenia 11%, febrile neutropenia 6%, nausea 8% and rash 8%. 20 patients achieved a partial response, 17 a stable disease, 2 were not evaluable. 37 patients (95%) underwent surgery and in three of them a complete pathological response was achieved. At a median follow-up of 44.2 months, 41% of the patients had died, median progression-free survival was 22.5 months. Conclusions Two cycles of cisplatin/ docetaxel/ cetuximab showed promising efficacy in the neoadjuvant treatment of early-stage NSCLC and rapid operation was possible in 95% of patients. Toxicities were manageable and as expected. Trial Registration EU Clinical Trials Register; Eudract-Nr: 2006-004639-31 PMID:26020783

  15. Urachal Carcinoma with Choroidal, Lung, Lymph Node, Adrenal, Mammary, and Bone Metastases and Peritoneal Carcinomatosis Showing Partial Response after Chemotherapy Treatment with a Modified Docetaxel, Cisplatin and 5-Fluorouracil Regimen

    PubMed Central

    Dekeister, Kathleen; Viguier, Jean Louis; Martin, Xavier; Nguyen, Anh Minh; Boyle, Helen; Flechon, Aude

    2016-01-01

    Urachal carcinoma (UC) is a rare tumor mainly affecting middle-aged males. Metastases occur most frequently in lymph nodes and the lungs. There are no standard adjuvant and metastatic treatments. We report the case of a 36-year-old female with UC treated with partial cystectomy who relapsed 3 years after surgery with left choroidal, lung, mediastinal lymph node, right adrenal, mammary, and bone metastases as well as peritoneal carcinomatosis. She obtained a partial response after 10 cycles of chemotherapy with a modified docetaxel, cisplatin and 5-fluorouracil (mTPF) regimen. This is the first report on the use of the mTPF regimen in UC and on the existence of choroidal, adrenal, and mammary metastases. PMID:27194981

  16. Structure Determination of Cisplatin-Amino Acid Analogues by Infrared Multiple Photon Dissociation Action Spectroscopy

    NASA Astrophysics Data System (ADS)

    He, Chenchen; Bao, Xun; Zhu, Yanlong; Strobehn, Stephen; Kimutai, Bett; Nei, Y.-W.; Chow, C. S.; Rodgers, M. T.; Gao, Juehan; Oomens, J.

    2015-06-01

    To gain a better understanding of the binding mechanism and assist in the optimization of relevant drug and chemical probe design, both experimental and theoretical studies were performed on a series of amino acid-linked cisplatin derivatives, including glycine-, lysine-, and ornithine-linked cisplatin, Gplatin, Kplatin, and Oplatin, respectively. Cisplatin, the first FDA-approved platinum-based anticancer drug, has been widely used in cancer chemotherapy. Its pharmacological mechanism has been identified as its ability to coordinate to genomic DNA, and guanine is its major target. In previous reports, cisplatin was successfully utilized as a chemical probe to detect solvent accessible sites in ribosomal RNA (rRNA). Among the amino-acid-linked cisplatin derivatives, Oplatin exhibits preference for adenine over guanine. The mechanism behind its different selectivity compared to cisplatin may relate to its potential of forming a hydrogen bond between the carboxylate group in Pt (II) complex and the 6-amino moiety of adenosine stabilizes A-Oplatin products. Tandem mass spectrometry analysis also indicates that different coordination sites of Oplatin on adenosine affect glycosidic bond stability. Infrared multiple photon dissociation (IRMPD) action spectroscopy experiments were performed on all three amino acid-linked cisplatin to characterize their structures. An extensive theoretical study has been performed on Gplatin to guide the selection of the most effective theory and basis set based on its geometric information. The results for Gplatin provide the foundation for characterization of the more complex amino acid-linked cisplatin derivatives, Oplatin and Kplatin. Structural and energetic information elucidated for these compounds, particularly Oplatin reveal the reason for its alternative selectivity compared to cisplatin.

  17. CKD-EPI and cockcroft-gault equations identify similar candidates for neoadjuvant chemotherapy in muscle-invasive bladder cancer.

    PubMed

    Pal, Sumanta K; Ruel, Nora; Villegas, Sergio; Chang, Mark; DeWalt, Kara; Wilson, Timothy G; Vogelzang, Nicholas J; Yuh, Bertram E

    2014-01-01

    Clinical guidelines suggest neoadjuvant cisplatin-based chemotherapy prior to cystectomy in the setting of muscle-invasive bladder cancer (MIBC). A creatinine clearance (CrCl) >60 mL/min is frequently used to characterize cisplatin-eligible patients, and use of the CKD-EPI equation to estimate CrCl has been advocated. From a prospectively maintained institutional database, patients with MIBC who received cystectomy were identified and clinicopathologic information was ascertained. CrCl prior to surgery was computed using three equations: (1) Cockcroft-Gault (CG), (2) CKD-EPI, and (3) MDRD. The primary objective was to determine if the CG and CKD-EPI equations identified a different proportion of patients who were cisplatin-eligible, based on an estimated CrCl of >60 mL/min. Cisplatin-eligibility was also assessed in subsets based on age, CCI score and race. Actuarial rates of neoadjuvant cisplatin-based chemotherapy use were also reported. Of 126 patients, 70% and 71% of patients were found to be cisplatin-eligible by the CKD-EPI and CG equations, respectively (P = 0.9). The MDRD did not result in significantly different characterization of cisplatin-eligibility as compared to the CKD-EPI and CG equations. In the subset of patients age >80, the CKD-EPI equation identified a much smaller proportion of cisplatin-eligible patients (25%) as compared to the CG equation (50%) or the MDRD equation (63%). Only 34 patients (27%) received neoadjuvant cisplatin-based chemotherapy. Of the 92 patients who did not receive neoadjuvant chemotherapy, 64% had a CrCl >60 mL/min by CG. In contrast to previous reports, the CKD-EPI equation does not appear to characterize a broader span of patients as cisplatin-eligible. Older patients (age >80) may less frequently be characterized as cisplatin-eligible by CKD-EPI. The discordance between actual rates of neoadjuvant chemotherapy use and rates of cisplatin eligibility suggest that other factors (e.g., patient and physician preference

  18. Referee: hyperthermia alone or combined with cisplatin in addition to radiotherapy for advanced uterine cervical cancer.

    PubMed

    Dahl, O; Mella, O

    2002-01-01

    There are two evidence based therapeutic options for locally advanced cervical cancer: Radiotherapy and concurrent chemotherapy (cisplatin alone or combined with other drugs) or radiation and hyperthermia, documented in randomised trials. The weight of evidence is less for the most advanced stages. Combination of all three options are currently tested in several centres with good clinical response and acceptable toxicity. Based on a pragmatic approach we propose to proceed with a trial selecting cisplatin concurrent with radiation therapy as the standard arm to be compared with the same regimen with the addition of hyperthermia once a week.

  19. Correlation of long non-coding RNA H19 expression with cisplatin-resistance and clinical outcome in lung adenocarcinoma.

    PubMed

    Wang, Qi; Cheng, Ningning; Li, Xuefei; Pan, Hui; Li, Chunyu; Ren, Shengxiang; Su, Chunxia; Cai, Weijing; Zhao, Chao; Zhang, Limin; Zhou, Caicun

    2017-01-10

    The acquired drug resistance would influence the efficacy of cisplatin-based chemotherapy in non-small-cell lung cancer. The present study aimed to investigate the correlation of long non-coding RNA (lncRNA) H19 with cisplatin-resistance and clinical outcome in lung adenocarcinoma. In our study, the expression of H19 in cisplatin-resistant A549/DDP cells was unregulated. Knockdown of H19 restored the response of A549/DDP cells to cisplatin. H19-mediated chemosensitivity enhancement was associated with metastasis, induction of G0/G1 cell-cycle arrest, cell proliferation, and increased apoptosis. Furthermore, lncRNA H19 expression was significantly related to TNM stage and metastasis (P = 0.012). Overexpression of H19 was negatively correlated with cisplatin-based chemotherapy response in patients. Patients with high H19 expression exhibited a significantly shorter median progression-free survival (PFS) [4.7 months] than the low-expression patients (6.3months) [P = 0.002]. In summary, H19-mediated regulation of cisplatin resistance in human lung adenocarcinoma cells is demonstrated for the first time. H19 could potentially serve as a molecular marker to predict the clinical outcomes of lung adenocarcinoma patients.

  20. Hydrolysis theory for cisplatin and its analogues based on density functional studies.

    PubMed

    Zhang, Y; Guo, Z; You, X Z

    2001-09-26

    reactions. Comparing with the computational results of gas-phase reactions, it can be concluded that the solvent effect should be considered to obtain an accurate hydrolysis picture. The most affected structural parameters after solvation are related to the equatorial plane of the TBP-like geometry. The results provide theoretical guidance on detailed understanding on the mechanism of the hydrolysis of cisplatin, which could be useful in the design of novel Pt-based anticancer agents.

  1. Doublet chemotherapy with cisplatin and pemetrexed is associated with a favorable outcome in patients with advanced non-squamous non-small-cell lung cancer who are eligible for bevacizumab and maintenance therapy

    PubMed Central

    Nakashima, Kazuhisa; Murakami, Haruyasu; Omori, Shota; Wakuda, Kazushige; Ono, Akira; Kenmotsu, Hirotsugu; Naito, Tateaki; Endo, Masahiro; Takahashi, Toshiaki

    2016-01-01

    The previous AVAPERL trial demonstrated that induction therapy with first-line cisplatin (CDDP), pemetrexed (PEM) and bevacizumab (BEV), followed by continuation maintenance therapy with PEM+BEV, improved the progression-free survival (PFS) and overall survival (OS) compared with BEV alone (median PFS, 10.2 vs. 6.6 months and median OS, 19.8 vs. 15.9 months, respectively) in patients with advanced non-squamous non-small-cell lung cancer (non-Sq NSCLC). However, those findings were based on selected patients who were eligible for BEV and maintenance therapy. To assess the efficacy of CDDP+PEM as first-line therapy in selected patients depending on their eligibility for BEV and maintenance therapy, consecutive patients with non-Sq NSCLC who received first-line chemotherapy with CDDP+PEM at the Shizuoka Cancer Center (Shizuoka, Japan) between July, 2009 and December, 2013 were retrospectively reviewed. A total of 160 patients were assessed, including 92 who were eligible and 68 who were not eligible for BEV treatment. In the BEV-eligible group, CDDP+PEM treatment followed by maintenance PEM exhibited significantly superior efficacy compared with that in the BEV-ineligible group (median PFS, 5.8 vs. 4.8 months, respectively, P=0.013; and median OS, 21.3 vs. 12.6 months, respectively, P=0.0025). In the BEV-eligible group, 60 patients were suitable for maintenance therapy with PEM (group A) and 32 patients were unsuitable (group B). In the BEV-ineligible group, 31 patients were suitable for maintenance therapy with PEM (group C) and 37 patients were unsuitable (group D). In group A, the median PFS and OS were 6.9 and 31.8 months, respectively, compared with 2.4 and 10.5 months in group B, 6.1 and 18.5 months in group C, and 2.8 and 7.7 months in group D. The PFS and OS in group A were significantly better compared with those in the other groups. Thus, the PFS and OS with CDDP+PEM were favorable among patients with advanced non-Sq NSCLC who were eligible for BEV and

  2. Doublet chemotherapy with cisplatin and pemetrexed is associated with a favorable outcome in patients with advanced non-squamous non-small-cell lung cancer who are eligible for bevacizumab and maintenance therapy.

    PubMed

    Nakashima, Kazuhisa; Murakami, Haruyasu; Omori, Shota; Wakuda, Kazushige; Ono, Akira; Kenmotsu, Hirotsugu; Naito, Tateaki; Endo, Masahiro; Takahashi, Toshiaki

    2016-11-01

    The previous AVAPERL trial demonstrated that induction therapy with first-line cisplatin (CDDP), pemetrexed (PEM) and bevacizumab (BEV), followed by continuation maintenance therapy with PEM+BEV, improved the progression-free survival (PFS) and overall survival (OS) compared with BEV alone (median PFS, 10.2 vs. 6.6 months and median OS, 19.8 vs. 15.9 months, respectively) in patients with advanced non-squamous non-small-cell lung cancer (non-Sq NSCLC). However, those findings were based on selected patients who were eligible for BEV and maintenance therapy. To assess the efficacy of CDDP+PEM as first-line therapy in selected patients depending on their eligibility for BEV and maintenance therapy, consecutive patients with non-Sq NSCLC who received first-line chemotherapy with CDDP+PEM at the Shizuoka Cancer Center (Shizuoka, Japan) between July, 2009 and December, 2013 were retrospectively reviewed. A total of 160 patients were assessed, including 92 who were eligible and 68 who were not eligible for BEV treatment. In the BEV-eligible group, CDDP+PEM treatment followed by maintenance PEM exhibited significantly superior efficacy compared with that in the BEV-ineligible group (median PFS, 5.8 vs. 4.8 months, respectively, P=0.013; and median OS, 21.3 vs. 12.6 months, respectively, P=0.0025). In the BEV-eligible group, 60 patients were suitable for maintenance therapy with PEM (group A) and 32 patients were unsuitable (group B). In the BEV-ineligible group, 31 patients were suitable for maintenance therapy with PEM (group C) and 37 patients were unsuitable (group D). In group A, the median PFS and OS were 6.9 and 31.8 months, respectively, compared with 2.4 and 10.5 months in group B, 6.1 and 18.5 months in group C, and 2.8 and 7.7 months in group D. The PFS and OS in group A were significantly better compared with those in the other groups. Thus, the PFS and OS with CDDP+PEM were favorable among patients with advanced non-Sq NSCLC who were eligible for BEV and

  3. Reduced expression of microRNA-27a modulates cisplatin resistance in bladder cancer by targeting the cystine/glutamate exchanger SLC7A11

    PubMed Central

    Drayton, Ross M; Dudziec, Ewa; Peter, Stefan; Bertz, Simone; Hartmann, Arndt; Bryant, Helen E; Catto, James WF

    2014-01-01

    Purpose Resistance to cisplatin-based chemotherapy is a major obstacle to bladder cancer treatment. We aimed to identify microRNAs that are dysregulated in cisplatin-resistant disease, ascertain how these contribute to a drug resistant phenotype and how this resistance might be overcome. Experimental Design MicroRNA expression in paired cisplatin resistant and sensitive cell lines was measured. Dysregulated microRNAs were further studied for their ability to mediate resistance. The nature of the cisplatin resistant phenotype was established by measurement of cisplatin/DNA adducts and intracellular glutathione. Candidate microRNAs were examined for their ability to (i) mediate resistance and (ii) alter the expression of a candidate target protein (SLC7A11); direct regulation of SLC7A11 was confirmed using a luciferase assay. SLC7A11 protein and mRNA, and microRNA-27a were quantified in patient tumour material. Results A panel of microRNAs were found to be dysregulated in cisplatin resistant cells. MicroRNA-27a was found to target the cystine/glutamate exchanger SLC7A11 and to contribute to cisplatin resistance through modulation of glutathione biosynthesis. In patients, SLC7A11 expression was inversely related to microRNA-27a expression, and those tumors with high mRNA expression or high membrane staining for SLC7A11 experienced poorer clinical outcomes. Resistant cell lines were resensitized by restoring microRNA-27a expression, or reducing SLC7A11 activity with an siRNA or with sulfasalazine. Conclusion Our findings indicate that microRNA-27a negatively regulates SLC7A11 in cisplatin-resistant bladder cancer, and shows promise as a marker for patients likely to benefit from cisplatin-based chemotherapy. SLC7A11 inhibition with sulfasalazine may be a promising therapeutic approach to the treatment of cisplatin-resistant disease. PMID:24516043

  4. Neoadjuvant chemotherapy for invasive bladder cancer.

    PubMed

    Sonpavde, Guru; Sternberg, Cora N

    2012-04-01

    Neoadjuvant cisplatin-based combination chemotherapy is an established standard for resectable muscle-invasive bladder cancer, a disease with a pattern of predominantly distant and early recurrences. Pathologic complete remission appears to be an intermediate surrogate for survival when employing combination chemotherapy. Moreover, baseline host and tumor tissue studies may enable the discovery of biomarkers predictive of activity. The neoadjuvant setting also provides a window of opportunity to evaluate novel biologic agents or rational combinations of biologic agents to obtain a signal of biologic activity. The residual tumor after neoadjuvant therapy may be exploited to study the mechanism of action and resistance. Cisplatin-ineligible patients warrant the evaluation of tolerable neoadjuvant regimens. Given that bladder cancer is characterized by initial localized presentation in the vast majority of cases, the paradigm of neoadjuvant therapy may expedite the development of novel systemic agents.

  5. Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial.

    PubMed

    Thatcher, Nick; Hirsch, Fred R; Luft, Alexander V; Szczesna, Aleksandra; Ciuleanu, Tudor E; Dediu, Mircea; Ramlau, Rodryg; Galiulin, Rinat K; Bálint, Beatrix; Losonczy, György; Kazarnowicz, Andrzej; Park, Keunchil; Schumann, Christian; Reck, Martin; Depenbrock, Henrik; Nanda, Shivani; Kruljac-Letunic, Anamarija; Kurek, Raffael; Paz-Ares, Luis; Socinski, Mark A

    2015-07-01

    Necitumumab is a second-generation, recombinant, human immunoglobulin G1 EGFR antibody. In this study, we aimed to compare treatment with necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone in patients with previously untreated stage IV squamous non-small-cell lung cancer. We did this open-label, randomised phase 3 study at 184 investigative sites in 26 countries. Patients aged 18 years or older with histologically or cytologically confirmed stage IV squamous non-small-cell lung cancer, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 and adequate organ function and who had not received previous chemotherapy for their disease were eligible for inclusion. Enrolled patients were randomly assigned centrally 1:1 to a maximum of six 3-week cycles of gemcitabine and cisplastin chemotherapy with or without necitumumab according to a block randomisation scheme (block size of four) by a telephone-based interactive voice response system or interactive web response system. Chemotherapy was gemcitabine 1250 mg/m(2) administered intravenously over 30 min on days 1 and 8 of a 3-week cycle and cisplatin 75 mg/m(2) administered intravenously over 120 min on day 1 of a 3-week cycle. Necitumumab 800 mg, administered intravenously over a minimum of 50 min on days 1 and 8, was continued after the end of chemotherapy until disease progression or intolerable toxic side-effects occurred. Randomisation was stratified by ECOG performance status and geographical region. Neither physicians nor patients were masked to group assignment because of the expected occurrence of acne-like rash--a class effect of EGFR antibodies--that would have unmasked most patients and investigators to treatment. The primary endpoint was overall survival, analysed by intention to treat. We report the final clinical analysis. This study is registered with ClinicalTrials.gov, number NCT00981058. Between Jan 7, 2010, and Feb 22, 2012, we enrolled 1093 patients

  6. Third-line chemotherapy and novel agents for metastatic germ cell tumors.

    PubMed

    Veenstra, Christine M; Vaughn, David J

    2011-06-01

    Although germ cell tumors (GCT) are among the most curable solid tumors, a subset of patients with GCT experience relapse or progression despite appropriate cisplatin-based therapy or first-line salvage therapy. This article describes the molecular mechanisms of cisplatin resistance, outlines single-agent chemotherapy and combination chemotherapy regimens that are active against GCT in the third-line or later setting, discusses the use of drug therapy for treating growing teratoma syndrome and teratoma with malignant transformation, outlines novel agents used to treat GCT, and highlights ongoing clinical trials and future directions in the treatment of refractory GCT. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Development of controlled-release cisplatin dry powders for inhalation against lung cancers.

    PubMed

    Levet, Vincent; Rosière, Rémi; Merlos, Romain; Fusaro, Luca; Berger, Gilles; Amighi, Karim; Wauthoz, Nathalie

    2016-12-30

    The present study focuses on the development of dry powders for inhalation as adjuvant chemotherapy in lung cancer treatment. Cisplatin was chosen as a potential candidate for a local treatment as it remains the main platinum component used in conventional chemotherapies, despite its high and cumulative systemic toxicities. Bulk cisplatin was reduced to submicron sizes using high-pressure homogenization, mixed with a solubilized lipid and/or PEGylated component and then spray-dried to produce controlled-release dry powder formulations. The obtained formulations were characterized for their physicochemical properties (particle size and morphology), aerodynamic performance and release profiles. Cisplatin content and integrity were assessed by electrothermal atomic absorption spectrometry and (195)Pt nuclear magnetic resonance spectroscopy. DPI formulations with cisplatin contents ranging from 48.5 to 101.0% w/w exhibited high fine particle fractions ranging from 37.3% to 51.5% of the nominal dose. Formulations containing cisplatin microcrystals dispersed in solid lipid microparticles based on acceptable triglycerides for inhalation and PEGylated excipients showed a controlled-release for more than 24h and a limited burst effect. These new formulations could provide an interesting approach to increasing and prolonging drug exposure in the lung while minimizing systemic toxicities.

  8. Resveratrol Attenuates Cisplatin Renal Cortical Cytotoxicity by Modifying Oxidative Stress

    PubMed Central

    Valentovic, Monica A.; Ball, John G.; Brown, J. Mike; Terneus, Marcus V.; McQuade, Elizabeth; Van Meter, Stephanie; Hedrick, Hayden M.; Roy, Amy Allison; Williams, Tierra

    2014-01-01

    Cisplatin, a cancer chemotherapy drug, is nephrotoxic. The aim of this study was to investigate whether resveratrol (RES) reduced cisplatin cytotoxicity and oxidative stress. Rat renal cortical slices were pre-incubated 30 min with 0 (VEH, ethanol) or 30 μg/ml RES followed by 60, 90 or 120 min co-incubation with 0, 75, or 150 μg/mL cisplatin. Lactate dehydrogenase (LDH) leakage was unchanged at 60 and 90 min by cisplatin. Cisplatin increased (p<0.05) LDH leakage at 120 min which was protected by RES. Cisplatin induced oxidative stress prior to LDH leakage as cisplatin depressed glutathione peroxidase and superoxide dismutase (SOD) activity, increased lipid peroxidation, protein carbonyls and 4-hydroxynonenal (4-HNE) adducted proteins within 60 min. RES failed to reverse glutathione (GSH) depression by cisplatin. In order to eliminated an extracellular interaction between RES and cisplatin, additional studies (RINSE studies) allowed a 30 min RES uptake into slices, transfer of slices to buffer lacking RES, followed by 120 min cisplatin incubation. RES in the RINSE studies prevented LDH leakage by cisplatin indicating that RES protection was not via a physical interaction with cisplatin in the media. These findings indicate that RES diminished cisplatin in vitro renal toxicity and prevented the development of oxidative stress. PMID:24239945

  9. [Preventive effect of polaprezinc suspension dispersed in sodium alginate solution (P-AG) for stomatitis induced by Docetaxel/Cisplatin/Fluorouracil (DCF) chemotherapy in patients with head and neck cancer].

    PubMed

    Sugisaki, Takahito; Kawakami, Kazuyoshi; Nemoto, Maki; Kawata, Keiji; Ishibashi, Michiko; Fujiki, Yukako; Mishima, Yuko; Yokoyama, Masahiro; Takahashi, Shunji; Hatake, Kiyohiko; Hama, Toshihiro

    2011-05-01

    We measured the effectiveness of the prophylactic administration of a polaprezinc suspension dispersed in sodium alginate solution (P-AG) by dividing it into two courses in the same patients, and measured the stomatitis induced by Docetaxel/Cisplatin/Fluorouracil (DCF) chemotherapy. We then evaluated the results. We defined the therapeutic course as the course where P-AG was given therapeutically for stomatitis induced after DCF chemotherapy. We defined the prophylactic course as when P-AG was prophylactically given before any incidences of stomatitis after the therapeutic course. We compared the incidences of stomatitis in the prophylactic courses with those of the therapeutic courses. The incidences of stomatitis that were higher than Grade 1 were 17 out of 17 patients (100%) in the therapeutic course. On the other hand, they were 15 out of 17 patients (88. 2%) in the prophylactic course. Compared with the mean of the Grade of Stomatitis by the Common Terminology Criteria for Adverse Events version 3. 0 (CTCAE v. 3. 0), the maximal Grade of stomatitis significantly decreased in the prophylactic courses compared to those of the therapeutic courses(p<0. 05). Therefore, these results suggested that we were able to decrease the severity of stomatitis by using P-AG prophylactically, as opposed to using P-AG therapeutically.

  10. Weekly chemotherapy with radiation versus high-dose cisplatin with radiation as organ preservation for patients with HPV-positive and HPV-negative locally advanced squamous cell carcinoma of the oropharynx.

    PubMed

    Dobrosotskaya, Irina Y; Bellile, Emily; Spector, Matthew E; Kumar, Bhavna; Feng, Felix; Eisbruch, Avraham; Wolf, Gregory T; Prince, Mark E P; Moyer, Jeffrey S; Teknos, Theodoros; Chepeha, Douglas B; Walline, Heather M; McHugh, Jonathan B; Cordell, Kitrina G; Ward, P Daniel; Byrd, Serena; Maxwell, Jessica H; Urba, Susan; Bradford, Carol R; Carey, Thomas E; Worden, Francis P

    2014-05-01

    Optimal treatment for locally advanced squamous cell carcinoma of the oropharynx (SCCOP) is not well defined. Here we retrospectively compare survival and toxicities from 2 different organ preservation protocols. The matched dataset consisted of 35 patients from each trial matched for age, stage, smoking, and tumor human papillomavirus (HPV) status. Patients in the University of Michigan Cancer Center (UMCC) trial 9921 were treated with induction chemotherapy (IC) followed by high-dose cisplatin and radiation in responders or surgery in nonresponders. Patients in the UMCC trial 0221 were treated with weekly carboplatin and paclitaxel and radiation. Survival was comparable for both studies and did not differ significantly across each trial after stratifying by HPV status. Grade 3 and 4 toxicities were more frequent in UMCC 9921. At 6 months posttreatment, gastrostomy tube (G-tube) dependence was not statistically different. These data suggest that survival outcomes in patients with locally advanced SCCOP are not compromised with weekly chemotherapy and radiation therapy, and such treatment is generally more tolerable. Copyright © 2013 Wiley Periodicals, Inc.

  11. Feasibility of preoperative combined radiation therapy and chemotherapy with 5-fluorouracil and cisplatin in potentially resectable pancreatic adenocarcinoma: The French SFRO-FFCD 97-04 Phase II trial

    SciTech Connect

    Mornex, Francoise . E-mail: francoise.mornex@chu-lyon.fr; Girard, Nicolas; Scoazec, Jean-Yves; Bossard, Nadine; Ychou, Marc; Smith, Denis; Seitz, Jean-Francois; Valette, Pierre-Jean; Roy, Pascal; Rouanet, Philippe; Ducreux, Michel; Partensky, Christian

    2006-08-01

    Purpose More than 80% of patients who undergo a potentially curative resection for pancreatic cancer develop local or distant recurrence. Neoadjuvant chemoradiotherapy might offer potential benefits regarding local and systemic control and survival. This multi-institutional Phase II trial explored the feasibility of preoperative chemoradiation in this situation. Methods and Materials Treatment consisted of concurrent radiotherapy (50 Gy within 5 weeks), and chemotherapy with 5-fluorouracil (300 mg/m{sup 2}/day, 5 days/week, 5 consecutive weeks) and cisplatin (20 mg/m{sup 2}/day, Days 1-5 and 29-33), followed by surgical resection of the pancreatic tumor in patients without progression. Results A total of 41 patients were enrolled. Of these, 38 (93%) received {>=}47 Gy; 30 patients (73%) received {>=}75% of the prescribed doses of chemotherapy. Surgical resection was performed in 26 patients (63%). Because of local or metastatic progression, 5 patients (12%) did not undergo surgery and 10 underwent surgery without resection of the pancreatic tumor. Operative mortality was 2.8%. Among 40 evaluable patients, 27 were successfully treated (67.5%; 95% CI, 50.9-81.4%). Conclusions Pancreatic cancer is chemo-radiosensitive. The proposed pre-operative scheme is feasible, does not prevent successful surgery, and must be tested on a Phase III setting. Yet, the large proportion of tumor progression during and after chemoradiation justifies the use of more efficient drugs such as Gemcitabine, and optimized radiotherapy including new techniques such as intensity-modulated radiation therapy.

  12. [A meta-analysis of the curative effects of carboplatin-based and cisplatin-based chemotherapeutic regimens on advance non-small cell lung cancer].

    PubMed

    Jiang, Jing-wei; Liang, Xiao-hua; Zhou, Xin-li; Huang, Ruo-fan

    2006-10-10

    To evaluate whether there is a difference in the curative effect of carboplatin-based and cisplatin-based chemotherapeutic regimens on advance non-small cell lung cancer (NSCLC). The databases PudMed, CENTRAL, and Chinese biomedical database were retrieved by using the key words "non-small cell lung cancer" or "carcinoma, non-small cell lung" so as to search the materials about the randomized controlled clinical trials that had compared the curative effects of carboplatin-based and cisplatin-based chemotherapeutic regimens on advance NSCLC. A meta-analysis was conducted. Eighteen documents about randomized controlled clinical trials, including 6478 patients, from the retrieved 3531 documents accorded to the demand of enrollment. The overall response rates of the carboplatin-based and cisplatin-based chemotherapeutic groups were both 27% (RR = 0.93, 95% CI = 0.86 approximately 1.01, P = 0.10). Neither funnel plot nor rank correlation test regarding response rate indicated the existence of publication bias (chi(2) = 18.63, P = 0.63). The 0ne-year survival rate of the carboplatin-based regimen group was 36%, not significantly different from that of the cisplatin-based regimen group (35%, RR = 1.04, 95% CI = 0.93 - 1.17, P = 0.5). Sensitive analysis confirmed the non-existence of differences in the overall response rate and one-year survival rate between these 2 groups. The curative effects of the carboplatin-based and cisplatin-based chemotherapeutic regimens are similar. The choice of carboplatin or cisplatin depends on the toxicity of the drugs and the patients' tolerance.

  13. BGP-15 - a novel poly(ADP-ribose) polymerase inhibitor - protects against nephrotoxicity of cisplatin without compromising its antitumor activity.

    PubMed

    Racz, Ildiko; Tory, Kalman; Gallyas, Ferenc; Berente, Zoltán; Osz, Erzsebet; Jaszlits, Laszlo; Bernath, Sandor; Sumegi, Balazs; Rabloczky, Gyorgy; Literati-Nagy, Peter

    2002-03-15

    Nephrotoxicity is one of the major dose limiting side effects of cisplatin chemotherapy. The antitumor and toxic effects are mediated in part by different mechanisms, thus, permitting a selective inhibition of certain side effects. The influence of O-(3-piperidino-2-hydroxy-1-propyl)nicotinic amidoxime (BGP-15) - a poly(ADP-ribose) polymerase (PARP) inhibitor - on the nephrotoxicity and antitumor efficacy of cisplatin has been evaluated in experimental models. BGP-15 either blocked or significantly reduced (60-90% in 100-200 mg/kg oral dose) cisplatin induced increase in serum urea and creatinine level in mice and rats and prevented the structural degeneration of the kidney, as well. The nephroprotective effect of BGP-15 treatment was revealed also in living mice by MRI analysis manifesting in the lack of oedema which otherwise developed as a result of cisplatin treatment. The protective effect was accompanied by inhibition of cisplatin-induced poly-ADP-ribosylation and by the restoration of the disturbed energy metabolism. The preservation of ATP level in the kidney was demonstrated in vivo by localized NMR spectroscopy. BGP-15 decreased cisplatin-induced ROS production in rat kidney mitochondria and improved the antioxidant status of the kidney in mice with cisplatin-induced nephropathy. In rat kidney, cisplatin caused a decrease in the level of Bcl-x, a mitochondrial protective protein, and this was normalized by BGP-15 treatment. On the other hand, BGP-15 did not inhibit the antitumor efficacy of cisplatin in cell culture and in transplantable solid tumors of mice. Treatment with BGP-15 increased the mean survival time of cisplatin-treated P-388 leukemia bearing mice from 13 to 19 days. PARP inhibitors have been demonstrated to diminish the consequences of free radical-induced damage, and this is related to the chemoprotective effect of BGP-15, a novel PARP inhibitor. Based on these results, we propose that BGP-15 represents a novel, non-thiol chemoprotective

  14. Neoadjuvant chemotherapy for bladder cancer.

    PubMed

    Black, Peter C; Brown, Gordon A; Grossman, H Barton; Dinney, Colin P

    2006-11-01

    The 30-45% failure rate after radical cystoprostatectomy mandates that we explore and optimize multimodal therapy to achieve better disease control in these patients. Cisplatin-based multi-agent combination chemotherapy has been used with success in metastatic disease and has therefore also been introduced in patients with high-risk but non-metastatic bladder cancer. There is now convincing evidence that chemotherapy given pre-operatively can improve survival in these patients. In this review we establish the need for peri-operative chemotherapy in bladder cancer patients and summarize the evidence for the efficacy of neoadjuvant chemotherapy. The advantages and disadvantages of neoadjuvant versus adjuvant chemotherapy are discussed, and the main shortcomings of both--treatment-related toxicity and the inability to prospectively identify likely responders--are presented. Finally, a risk-adapted approach to neoadjuvant chemotherapy is presented, whereby the highest risk patients are offered treatment while those unlikely to benefit are spared the treatment-related toxicity.

  15. [50th anniversary of cisplatin].

    PubMed

    Rancoule, Chloé; Guy, Jean-Baptiste; Vallard, Alexis; Ben Mrad, Majed; Rehailia, Amel; Magné, Nicolas

    2017-02-01

    We have just celebrated the 50th anniversary of cisplatin cytotoxic potential discovery. It is time to take stock… and it seems mainly positive. This drug, that revolutionized the treatment of many cancer types, continues to be the most widely prescribed chemotherapy. Despite significant toxicities, resistance mechanisms associated with treatment failures, and unresolved questions about its mechanism of action, the use of this cytotoxic agent remains unwavering. The interest concerning this "old" invincible drug has not yet abated. Indeed many research axes are in the news. New platinum salts agents are tested, new cisplatin formulations are developed to target tumor cells more efficiently, and new combinations are established to increase the cytotoxic potency of cisplatin or overcome the resistance mechanisms.

  16. Quality of life analysis of TORCH, a randomized trial testing first-line erlotinib followed by second-line cisplatin/gemcitabine chemotherapy in advanced non-small-cell lung cancer.

    PubMed

    Di Maio, Massimo; Leighl, Natasha B; Gallo, Ciro; Feld, Ronald; Ciardiello, Fortunato; Butts, Charles; Maione, Paolo; Gebbia, Vittorio; Morgillo, Floriana; Wierzbicki, Rafal; Favaretto, Adolfo; Alam, Yasmin; Cinieri, Saverio; Siena, Salvatore; Bianco, Roberto; Riccardi, Ferdinando; Spatafora, Mario; Ravaioli, Alberto; Felletti, Raffaella; Fregoni, Vittorio; Genestreti, Giovenzio; Rossi, Antonio; Mancuso, Gianfranco; Fasano, Morena; Morabito, Alessandro; Tsao, Ming Sound; Signoriello, Simona; Perrone, Francesco; Gridelli, Cesare

    2012-12-01

    The TORCH (Tarceva or Chemotherapy) trial randomized patients with advanced non-small-cell lung cancer to first-line erlotinib followed by second-line cisplatin/gemcitabine versus. standard inverse sequence. The trial, designed to test noninferiority in overall survival, was stopped at interim analysis because of inferior survival in the experimental arm. Quality of life (QoL), a secondary outcome, is reported here. QoL was assessed at baseline and every 3 weeks during first-line, using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 and QLQ-lung cancer specific module (LC13). Mean changes from baseline within arms were reported. QoL response and time-to-deterioration of QoL using a competing-risk approach were compared between treatment arms. Six hundred and thirty patients (83%) completed baseline questionnaires. Compliance was affected by differential treatment efficacy, but was similar between arms for patients without progression or death. Significant differences in QoL responses were observed favoring chemotherapy for pain, sleeping, dyspnea, diarrhea, and favoring erlotinib for vomiting, constipation, sore mouth, and alopecia. In the small subset of patients with EGFR-mutated tumors, all selected items (global QoL, physical functioning, cough, dyspnea and pain) improved, whereas worsening or no change was observed in wild-type patients. Improvement was particularly evident in the first-line erlotinib arm as for global QoL and physical functioning. QoL was impacted by differential toxicity and efficacy between arms. Functional domains and global QoL did not differ, although some symptoms were better controlled with chemotherapy in unselected non-small-cell lung cancer patients.

  17. Analysis of genetic and non genetic risk factors for cisplatin ototoxicity in pediatric patients.

    PubMed

    Olgun, Yüksel; Aktaş, Safiye; Altun, Zekiye; Kırkım, Günay; Kızmazoğlu, Deniz Çakır; Erçetin, Ayşe Pınar; Demir, Banu; İnce, Dilek; Mutafoğlu, Kamer; Demirağ, Bengü; Ellidokuz, Hülya; Olgun, Nur; Güneri, Enis Alpin

    2016-11-01

    The aim of this study was to analyse the genetic and non genetic risk factors for cisplatin ototoxicity. This study was conducted on 72 children who received cisplatin based chemotherapy. Brock and Muenster classifications were used to evaluate ototoxicity seen in these children. 6 single nucleotide polymorphisms (SNP); ERCC1 rs 11615, GSTP1 rs1138272, GSTP1 rs1695, LRP2 rs 2075252, TPMT rs 12201199, COMT rs 9332377, were evaluated as genetic factors by real time PCR. Non genetic factors such as cranial irradiation, cumulative doses of cisplatin, age, gender, administration of other ototoxic drugs were analysed as well. By using Chi-square test, risk factors were matched with the ototoxicity classifications. Significant risk factors were reevaluated using logistic regression modelling. According to univariate analyses, male gender, co-treatment with aminoglycosides and mutant genotype of GSTP1 rs1695 were significantly related with cisplatin ototoxicity. Logistic regression modelling analyses also showed that male gender, co-treatment with aminoglycosides were found to be significantly related with cisplatin ototoxicity. Mutant genotype of GSTP1 rs1695 was not found to be significant, but close to the level of statistical significance. Male gender, co-treatment with aminoglycosides are significant risk factors for cisplatin ototoxicity in pediatric patients. Mutant genotype of GSTP1 rs1695 seems to be a genetic risk factor in univariate analyses, although not confirmed by multivariate analyses. Therefore, GSTP1 rs1695 SNP needs to be studied in larger series. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. IL-17A exacerbates cisplatin-based resistance of OVCA via upregulating the expression of ABCG2 and MDR1 through Gli1-mediated Hh signaling.

    PubMed

    Niu, Xiulong; Liu, Wenxing; Wang, Yue; Liu, Xiaomei; Zhang, Hongjian; Li, Zhijun; Li, Hongzhao; Iwakura, Yoichiro; Deng, Weimin

    2016-07-18

    The major obstacle of the tumor chemotherapy, including ovarian cancer (OVCA), is drug resistance. However, the relevance of IL-17A with drug-resistance of OVCA has been poorly elaborated. In this study, we used 2 human OVCA cell lines to investigate the effects of IL-17A on cisplatin (CDDP or DDP)-based resistance in OVCA cells and the underlying mechanisms. Meanwhile, IL-17A-deficient mice and ID8 were used to verify the IL-17A's effects on OVCA chemo-resistance in vivo. Moreover, the relationship between IL-17A level and relevant indices were primarily assessed in ovarian specimens from 55 patients with OVCA. We found that rhIL-17A exacerbated DDP-based resistance of OVCA cells via up-regulating the expression of ABCG2 and MDR1 through Gli1-mediated Hh signal pathway. Animal experiment demonstrated that IL-17A significantly recede DDP-based treatment for ID8 tumor. Similar results were observed in preliminary clinical investigation. Our findings suggest that inhibiting IL-17A/IL-17RA-Gli1 signal may improve the resistance of OVCA to DDP.

  19. MLN4924 Synergistically Enhances Cisplatin-induced Cytotoxicity via JNK and Bcl-xL Pathways in Human Urothelial Carcinoma.

    PubMed

    Ho, I-Lin; Kuo, Kuan-Lin; Liu, Shing-Hwa-; Chang, Hong-Chiang; Hsieh, Ju-Ton; Wu, June-Tai; Chiang, Chih-Kang; Lin, Wei-Chou; Tsai, Yu-Chieh; Chou, Chien-Tso; Hsu, Chen-Hsun; Pu, Yeong-Shiau; Shi, Chung-Sheng; Huang, Kuo-How

    2015-11-23

    Cisplatin-based chemotherapy is the primary treatment for metastatic bladder urothelial carcinoma. However, the response rate is only 40-65%. This study investigated the anti-tumor effect and underlying mechanisms of the combination of cisplatin and the NEDD8-activating enzyme inhibitor MLN4924 in human bladder urothelial carcinoma. The combination of cisplatin and MLN4924 exerted synergistic cytotoxicity on two high-grade bladder urothelial carcinoma cell lines, NTUB1 and T24 (combination index <1). MLN4924 also potentiated the cisplatin-induced apoptosis and activation of caspase-3 and -7, phospho-histone H2A.X and PARP. c-Jun N-terminal kinase (JNK) activation and a down-regulation of B-cell lymphoma-extra large (Bcl-xL) were also observed during cisplatin and MLN4924 treatment. Inhibition of JNK activation partially restored cell viability and Bcl-xL expression. Bcl-xL overexpression also rescued cell viability. MLN4924 significantly potentiated cisplatin-induced tumor suppression in urothelial carcinoma xenograft mice. In summary, MLN4924 synergistically enhanced the anti-tumor effect of cisplatin via an increase in DNA damage, JNK activation and down-regulation of Bcl-xL in urothelial carcinoma cells. These findings provide a new therapeutic strategy for the treatment of bladder cancer.

  20. Cisplatin-induced ototoxicity in pediatric solid tumors: the role of glutathione S-transferases and megalin genetic polymorphisms.

    PubMed

    Choeyprasert, Worawut; Sawangpanich, Rachchadol; Lertsukprasert, Krisna; Udomsubpayakul, Umaporn; Songdej, Duantida; Unurathapan, Usanarat; Pakakasama, Samart; Hongeng, Suradej

    2013-05-01

    Cisplatin-induced ototoxicity, an important dose-limiting side effect, has proven high interindividual variability. Glutathione S-transferases (GSTs) are isoenzymes involved in cellular detoxification processes. Megalin has been demonstrated to bind aminoglycosides, known to be similar to cisplatin for their ototoxicity. The GSTs and megalin expression is genetically polymorphic, which might be responsible for the variability in cisplatin-induced ototoxicity. The genotyping of GSTM1, GSTT1 polymorphisms, and 2 nonsynonymous single nucleotide polymorphisms (SNPs) at megalin genes, rs2075252 and rs2228171, were performed in 68 children diagnosed with solid tumors who received cisplatin-based chemotherapy. After the end of treatment, audiometry demonstrated hearing loss in 79.4% of patients according to Brock classification. The cumulative cisplatin dose >400 mg/m is associated with increased risk of cisplatin-induced ototoxicity [odds ratio (OR), 17.5; 95% confidence interval (CI), 3.09-98.62]. GSTT1 wild genotype and C-allele of rs2228171 SNPs of megalin gene occurred with higher frequency in patients with ototoxicity (P=0.023; OR, 10; 95% CI, 1.80-56.00 and P=0.034; OR, 2.67; 95% CI, 1.22-5.82, respectively). In conclusion, our results suggested that GSTT1 wild genotype and C-allele of rs2228171 SNPs might be risk factors for ototoxicity. The cumulative cisplatin dose <400 mg/m should be beneficial in order to ameliorate ototoxicity.

  1. BRCA1 epigenetic inactivation predicts sensitivity to platinum-based chemotherapy in breast and ovarian cancer

    PubMed Central

    Stefansson, Olafur A.; Villanueva, Alberto; Vidal, August; Martí, Lola; Esteller, Manel

    2012-01-01

    Germline mutations in the BRCA1 or BRCA2 genes are associated with an increased risk of breast and ovarian cancer development. Both genes are involved in DNA repair, and tumors harboring genetic defects in them are thought to be more sensitive to DNA-damaging agents used in chemotherapy. However, as only a minority of breast and ovarian cancer patients carry BRCA1 or BRCA2 mutations, few patients are likely to benefit from these pharmacogenetic biomarkers. Herein, we show that, in cancer cell lines and xenografted tumors, BRCA1 CpG island promoter hypermethylation-associated silencing also predicts enhanced sensitivity to platinum-derived drugs to the same extent as BRCA1 mutations. Most importantly, BRCA1 hypermethylation proves to be a predictor of longer time to relapse and improved overall survival in ovarian cancer patients undergoing chemotherapy with cisplatin. PMID:23069641

  2. Mobile Phone Based System Opportunities to Home-based Managing of Chemotherapy Side Effects

    PubMed Central

    Davoodi, Somayeh; Mohammadzadeh, Zeinab; Safdari, Reza

    2016-01-01

    Objective: Applying mobile base systems in cancer care especially in chemotherapy management have remarkable growing in recent decades. Because chemotherapy side effects have significant influences on patient’s lives, therefore it is necessary to take ways to control them. This research has studied some experiences of using mobile phone based systems to home-based monitor of chemotherapy side effects in cancer. Methods: In this literature review study, search was conducted with keywords like cancer, chemotherapy, mobile phone, information technology, side effects and self managing, in Science Direct, Google Scholar and Pub Med databases since 2005. Results: Today, because of the growing trend of the cancer, we need methods and innovations such as information technology to manage and control it. Mobile phone based systems are the solutions that help to provide quick access to monitor chemotherapy side effects for cancer patients at home. Investigated studies demonstrate that using of mobile phones in chemotherapy management have positive results and led to patients and clinicians satisfactions. Conclusion: This study shows that the mobile phone system for home-based monitoring chemotherapy side effects works well. In result, knowledge of cancer self-management and the rate of patient’s effective participation in care process improved. PMID:27482134

  3. Mobile Phone Based System Opportunities to Home-based Managing of Chemotherapy Side Effects.

    PubMed

    Davoodi, Somayeh; Mohammadzadeh, Zeinab; Safdari, Reza

    2016-06-01

    Applying mobile base systems in cancer care especially in chemotherapy management have remarkable growing in recent decades. Because chemotherapy side effects have significant influences on patient's lives, therefore it is necessary to take ways to control them. This research has studied some experiences of using mobile phone based systems to home-based monitor of chemotherapy side effects in cancer. In this literature review study, search was conducted with keywords like cancer, chemotherapy, mobile phone, information technology, side effects and self managing, in Science Direct, Google Scholar and Pub Med databases since 2005. Today, because of the growing trend of the cancer, we need methods and innovations such as information technology to manage and control it. Mobile phone based systems are the solutions that help to provide quick access to monitor chemotherapy side effects for cancer patients at home. Investigated studies demonstrate that using of mobile phones in chemotherapy management have positive results and led to patients and clinicians satisfactions. This study shows that the mobile phone system for home-based monitoring chemotherapy side effects works well. In result, knowledge of cancer self-management and the rate of patient's effective participation in care process improved.

  4. Cisplatin and Aminoglycoside Antibiotics: Hearing Loss and Its Prevention

    PubMed Central

    Schacht, Jochen; Talaska, Andra E.; Rybak, Leonard P.

    2013-01-01

    This review introduces the pathology of aminoglycoside antibiotic and the cisplatin chemotherapy classes of drugs, discusses oxidative stress in the inner ear as a primary trigger for cell damage, and delineates the ensuing cell death pathways. Among potentially ototoxic (damaging the inner ear) therapeutics, the platinum-based anti-cancer drugs and the aminoglycoside antibiotics are of critical clinical importance. Both drugs cause sensorineural hearing loss in patients, a side effect that can be reproduced in experimental animals. Hearing loss is reflected primarily in damage to outer hair cells, beginning in the basal turn of the cochlea. In addition, aminoglycosides might affect the vestibular system while cisplatin seems to have a much lower likelihood to do so. Finally, based on an understanding the mechanisms of ototoxicity pharmaceutical ways of protection of the cochlea are presented PMID:23045231

  5. High pathological response rate in locally advanced esophageal cancer after neoadjuvant combined modality therapy: dose finding of a weekly chemotherapy schedule with protracted venous infusion of 5-fluorouracil and dose escalation of cisplatin, docetaxel and concurrent radiotherapy.

    PubMed

    Pasini, F; de Manzoni, G; Pedrazzani, C; Grandinetti, A; Durante, E; Gabbani, M; Tomezzoli, A; Griso, C; Guglielmi, A; Pelosi, G; Maluta, S; Cetto, G L; Cordiano, C

    2005-07-01

    This phase I study was aimed at defining the toxicity profile and pathological response rate of a neoadjuvant schedule including weekly docetaxel and cisplatin, protracted venous infusion (PVI) of 5-FU and concomitant radiotherapy (RT) in locally advanced esophageal cancer. The schedule consisted of a first phase of chemotherapy alone and a second phase of concurrent chemoradiation. Initial doses were: docetaxel and cisplatin 20 mg/m2 on days 1, 8, 15, 29, 36 and 43 plus 5-FU 150 mg/m2 PVI on days 1-21 and 29-49; RT (40 Gy) started on day 29. In the following steps the doses were escalated up to docetaxel 35 mg/m2 and cisplatin 25 mg/m2 on days 1, 8, 15, 29, 36, 43, 50 and 57 plus 5-FU 180 mg/m2 PVI on days 1-21 and 150 mg/m2 PVI on days 29-63 concurrently with RT 50 Gy. Forty-seven patients were enrolled and 46 completed the planned treatment. During the concomitant phase, grade 3-4 hematological toxicities occurred in three patients (6.5%) (or 3/174 cycles) and non-hematological toxicities in six patients (13%) (or 7/179 cycles). A pathological downstaging was obtained in 59.6% of the cases (28/47): complete remission (pCR) in 14 patients, near pCR (residual microfoci on the primary pN0) in eight patients, pT2 pN0 in three patients and partial response on the primary with positive lymph nodes in three patients. Six (13%) and 13 (28%) patients were considered stable and non-responders, respectively. In the last dose level, eight pCR and four near-pCR were obtained out of 15 patients. The maximum tolerable dose was not formally defined because dose escalation was stopped at the last dose level. This schedule represents a feasible treatment and the high pathological response rate is extremely encouraging; the doses found in the last dose-level are the basis for an ongoing phase II study at our institution.

  6. Chemotherapy in advanced ovarian cancer: four systematic meta-analyses of individual patient data from 37 randomized trials. Advanced Ovarian Cancer Trialists' Group.

    PubMed Central

    Aabo, K.; Adams, M.; Adnitt, P.; Alberts, D. S.; Athanazziou, A.; Barley, V.; Bell, D. R.; Bianchi, U.; Bolis, G.; Brady, M. F.; Brodovsky, H. S.; Bruckner, H.; Buyse, M.; Canetta, R.; Chylak, V.; Cohen, C. J.; Colombo, N.; Conte, P. F.; Crowther, D.; Edmonson, J. H.; Gennatas, C.; Gilbey, E.; Gore, M.; Guthrie, D.; Yeap, B. Y.

    1998-01-01

    The purpose of this systematic study was to provide an up to date and reliable quantitative summary of the relative benefits of various types of chemotherapy (non-platinum vs platinum, single-agent vs combination and carboplatin vs cisplatin) in the treatment of advanced ovarian cancer. Also, to investigate whether well-defined patient subgroups benefit more or less from cisplatin- or carboplatin-based therapy. Meta-analyses were based on updated individual patient data from all available randomized controlled trials (published and unpublished), including 37 trials, 5667 patients and 4664 deaths. The results suggest that platinum-based chemotherapy is better than non-platinum therapy, show a trend in favour of platinum combinations over single-agent platinum, and suggest that cisplatin and carboplatin are equally effective. There is no good evidence that cisplatin is more or less effective than carboplatin in any particular subgroup of patients. Images Figure 1 Figure 2 Figure 3 PMID:9836481

  7. Cisplatin and cranial irradiation-related hearing loss in children.

    PubMed

    Warrier, Rajasekharan; Chauhan, Aman; Davluri, Murali; Tedesco, Sonya L; Nadell, Joseph; Craver, Randall

    2012-01-01

    High doses of cisplatin and cranial radiotherapy (CRT) have been reported to cause irreversible hearing loss. The objective of this study was to examine the influence of cranial irradiation on cisplatin-associated ototoxicity in children with pediatric malignancies. Serial audiograms were obtained for 33 children, age <16 years, treated with cisplatin-based chemotherapy (90-120 mg/m(2) per cycle) with or without CRT. Eligible patients included those with normal baseline audiometric evaluations and without significant exposure to other ototoxic drugs. We defined significant hearing loss as a hearing threshold ≥30 dB at 2,000-8,000 Hz frequencies. The median age of our study population was 4.9 years (range 6 weeks to 16 years), and the male to female ratio was 0.8:1. The study population consisted of 15 Caucasians, 17 African-Americans, and 1 Hispanic. Fourteen patients had brain tumors, and 19 had other solid tumors. Thirteen patients were exposed to CRT, and 20 were not. Bilateral hearing loss was observed in 24/33 (73%) patients, with severe/profound (≥70 dB) impairment in 10/33 (30%) of all patients. Young age (<5 years), CRT, and brain tumors were independent prognostic factors predicting hearing loss. The study demonstrated a high incidence of hearing loss in children treated with cisplatin and CRT. Consequently, we recommend monitoring these children for the early detection of hearing loss.

  8. Cisplatin and Cranial Irradiation-Related Hearing Loss in Children

    PubMed Central

    Warrier, Rajasekharan; Chauhan, Aman; Davluri, Murali; Tedesco, Sonya L.; Nadell, Joseph; Craver, Randall

    2012-01-01

    Background: High doses of cisplatin and cranial radiotherapy (CRT) have been reported to cause irreversible hearing loss. The objective of this study was to examine the influence of cranial irradiation on cisplatin-associated ototoxicity in children with pediatric malignancies. Methods: Serial audiograms were obtained for 33 children, age <16 years, treated with cisplatin-based chemotherapy (90-120 mg/m2 per cycle) with or without CRT. Eligible patients included those with normal baseline audiometric evaluations and without significant exposure to other ototoxic drugs. We defined significant hearing loss as a hearing threshold ≥30 dB at 2,000-8,000 Hz frequencies. Results: The median age of our study population was 4.9 years (range 6 weeks to 16 years), and the male to female ratio was 0.8:1. The study population consisted of 15 Caucasians, 17 African-Americans, and 1 Hispanic. Fourteen patients had brain tumors, and 19 had other solid tumors. Thirteen patients were exposed to CRT, and 20 were not. Bilateral hearing loss was observed in 24/33 (73%) patients, with severe/profound (≥70 dB) impairment in 10/33 (30%) of all patients. Young age (<5 years), CRT, and brain tumors were independent prognostic factors predicting hearing loss. Conclusion: The study demonstrated a high incidence of hearing loss in children treated with cisplatin and CRT. Consequently, we recommend monitoring these children for the early detection of hearing loss. PMID:23049454

  9. Targeting Mechanisms of Resistance to Taxane-Based Chemotherapy

    DTIC Science & Technology

    2006-09-01

    chemotherapy resistance and uncover mechanisms or pathways suitable for targeting with the objective of improving tumor responses to chemotherapy. Gene ...excluding possible ischemia-related genes , the expression of 53 genes were significantly altered after chemotherapy. Several cytokines were...to identified 33 significantly-altered genes . IL8 was not only shown to be activated after chemotherapy but also have higher expression levels in the

  10. EGCG Enhances Cisplatin Sensitivity by Regulating Expression of the Copper and Cisplatin Influx Transporter CTR1 in Ovary Cancer

    PubMed Central

    Wang, Xuemin; Jiang, Pan; Wang, Pengqi; Yang, Chung S.; Wang, Xuerong; Feng, Qing

    2015-01-01

    Cisplatin is one of the first-line platinum-based chemotherapeutic agents for treatment of many types of cancer, including ovary cancer. CTR1 (copper transporter 1), a transmembrane solute carrier transporter, has previously been shown to increase the cellular uptake and sensitivity of cisplatin. It is hypothesized that increased CTR1 expression would enhance the sensitivity of cancer cells to cisplatin (cDDP). The present study demonstrates for the first time that (-)-epigallocatechin-3-gallate (EGCG), a major polyphenol from green tea, can enhance CTR1 mRNA and protein expression in ovarian cancer cells and xenograft mice. EGCG inhibits the rapid degradation of CTR1 induced by cDDP. The combination of EGCG and cDDP increases the accumulation of cDDP and DNA-Pt adducts, and subsequently enhances the sensitivity of ovarian cancer SKOV3 and OVCAR3 cells to the chemotherapeutic agent. In the OVCAR3 ovarian cancer xenograft nude mice model, the combination of the lower concentration of cDDP and EGCG strongly repressed the tumor growth and exhibited protective effect on the nephrotoxicity induced by cisplatin. Overall, these findings uncover a novel chemotherapy mechanism of EGCG as an adjuvant for the treatment of ovarian cancer. PMID:25927922

  11. Riboflavin Ameliorates Cisplatin Induced Toxicities under Photoillumination

    PubMed Central

    Hassan, Iftekhar; Chibber, Sandesh; Khan, Aijaz A.; Naseem, Imrana

    2012-01-01

    Background Cisplatin is an effective anticancer drug that elicits many side effects mainly due to induction of oxidative and nitrosative stresses during prolonged chemotherapy. The severity of these side effects consequently restricts its clinical use under long term treatment. Riboflavin is an essential vitamin used in various metabolic redox reactions in the form of flavin adenine dinucleotide and flavin mononucleotide. Besides, it has excellent photosensitizing property that can be used to ameliorate these toxicities in mice under photodynamic therapy. Methods and Findings Riboflavin, cisplatin and their combinations were given to the separate groups of mice under photoilluminated condition under specific treatment regime. Their kidney and liver were excised for comet assay and histopathological studies. Furthermore, Fourier Transform Infrared Spectroscopy of riboflavin-cisplatin combination in vitro was also conducted to investigate any possible interaction between the two compounds. Their comet assay and histopathological examination revealed that riboflavin in combination with cisplatin was able to protect the tissues from cisplatin induced toxicities and damages. Moreover, Fourier Transform Infrared Spectroscopy analysis of the combination indicated a strong molecular interaction among their constituent groups that may be assigned for the protective effect of the combination in the treated animals. Conclusion Inclusion of riboflavin diminishes cisplatin induced toxicities which may possibly make the cisplatin-riboflavin combination, an effective treatment strategy under chemoradiotherapy in pronouncing its antineoplastic activity and sensitivity towards the cancer cells as compared to cisplatin alone. PMID:22567145

  12. Randomized Phase II Study of Adjuvant Chemotherapy with Long-term S-1 versus Cisplatin+S-1 in Completely Resected Stage II-IIIA Non-Small Cell Lung Cancer.

    PubMed

    Iwamoto, Yasuo; Mitsudomi, Tetsuya; Sakai, Kazuko; Yamanaka, Takeharu; Yoshioka, Hiroshige; Takahama, Makoto; Yoshimura, Masahiro; Yoshino, Ichiro; Takeda, Masayuki; Sugawara, Shunichi; Kawaguchi, Tomoya; Takahashi, Toshiaki; Ohta, Mitsunori; Ichinose, Yukito; Atagi, Shinji; Okada, Morihito; Saka, Hideo; Nakagawa, Kazuhiko; Nakanishi, Yoichi; Nishio, Kazuto

    2015-12-01

    The aims of this study were to evaluate the efficacy and safety of S-1 versus cisplatin (CDDP)+S-1 in patients with completely resected stage II and IIIA non-small cell lung cancer, and to identify predictive biomarkers whose expression in the tumors was significantly associated with patient outcome. A total of 200 patients were randomly assigned to receive either S-1 (40 mg/m(2) twice per day) for 2 consecutive weeks repeated every 3 weeks for 1 year (S group) or CDDP (60 mg/m(2)) on day 1 plus oral S-1 (40 mg/m(2) twice per day) for 2 consecutive weeks repeated every 3 weeks for four cycles (CS group) within 8 weeks after surgery. The primary endpoints were relapse-free survival (RFS) at 2 years and identification of predictive biomarkers whose expressions have been reported to be associated with CDDP or fluoropyrimidine sensitivity. The RFS rate at 2 years was 65.6% (95% confidence intervals; CI, 55.3-74.0%) in the S group and 58.1% (95% CI, 47.7-67.2%) in the CS group. The only gene with interaction of P < 0.05 was uridine monophosphate synthase (UMPS; P = 0.0348). The benefit that members of the S group had over members of the CS group was higher expression of UMPS. In vitro and in vivo experiments confirmed that overexpression of UMPS enhanced the antitumor effect of fluoropyrimidine. Adjuvant S-1 monotherapy might be preferable to CDDP+S-1 for patients with completely resected NSCLC. UMPS expression may define a patient subset that would benefit from long-term postoperative S-1 monotherapy. ©2015 American Association for Cancer Research.

  13. Chemotherapy in advanced bladder cancer: current status and future

    PubMed Central

    2011-01-01

    Bladder cancer occurs in the majority of cases in males. It represents the seventh most common cancer and the ninth most common cause of cancer deaths for men. Transitional cell carcinoma is the most predominant histological type. Bladder cancer is highly chemosensitive. In metastatic setting, chemotherapy based on cisplatin should be considered as standard treatment of choice for patients with good performance status (0-1) and good renal function-glomerular filtration rate (GFR) > 60 mL/min. The standard treatment is based on cisplatin chemotherapy regimens type MVAC, HD-MVAC, gemcitabine plus cisplatin (GC) or dose dense GC. In unfit patients, carboplatin based regimes; gemcitabine plus carboplatin or methotrexate plus carboplatin plus vinblastine (MCAVI) are reasonable options. The role of targeted therapies when used alone, or in combination with chemotherapy, or in maintenance, was evaluated; targeting angiogenesis seem to be very promising. The purpose of this literature review is to highlight the role of chemotherapy in the management of advanced transitional cell carcinoma of the bladder. PMID:21906310

  14. Role of ABC transporters in fluoropyrimidine-based chemotherapy response.

    PubMed

    Nies, Anne T; Magdy, Tarek; Schwab, Matthias; Zanger, Ulrich M

    2015-01-01

    Since over 50 years, 5-fluorouracil (5-FU) is in use as backbone of chemotherapy treatment regimens for a wide range of cancers including colon, breast, and head and neck carcinomas. However, drug resistance and severe toxicities such as mucositis, diarrhea, neutropenia, and vomiting in up to 40% of treated patients often lead to dose limitation or treatment discontinuation. Because the oral bioavailability of 5-FU is unpredictable and highly variable, 5-FU is commonly administered intravenously. To overcome medical complications and inconvenience associated with intravenous administration, the oral prodrugs capecitabine and tegafur have been developed. Both fluoropyrimidines are metabolically converted intracellularly to 5-FU, which then needs metabolic activation to exert its damaging activity on RNA and DNA. The low response rates of 10-15% of 5-FU monotherapy can be improved by combination regimens of infusional 5-FU and leucovorin together with oxaliplatin (FOLFOX) or irinotecan (FOLFIRI), thereby increasing response rates to 30-40%. The impact of metabolizing enzymes in the development of fluoropyrimidine toxicity and resistance has been studied in great detail. In addition, membrane drug transporters, which are critical determinants of intracellular drug concentrations, may play a role in occurrence of toxicity and development of resistance against fluoropyrimidine-based therapy as well. This review therefore summarizes current knowledge on the role of drug transporters with particular focus on ATP-binding cassette transporters in fluoropyrimidine-based chemotherapy response.

  15. Cisplatin Induces Differentiation of Breast Cancer Cells

    PubMed Central

    Prabhakaran, Praseetha; Hassiotou, Foteini; Blancafort, Pilar; Filgueira, Luis

    2013-01-01

    Breast tumors are heterogeneous including cells with stem cell properties and more differentiated cells. This heterogeneity is reflected into the molecular breast cancer subtypes. Breast cancer stem cells are resistant to chemotherapy, thus recent efforts are focusing on identifying treatments that shift them toward a more differentiated phenotype, making them more susceptible to chemotherapy. We examined whether the drug cisplatin induces differentiation in breast cancer cell lines that represent different breast cancer subtypes. We used three cell lines representing triple-negative breast cancers, BT-549 and MDA-MB-231 (claudin-low), and MDA-MB-468 (basal-like), along with estrogen and progesterone receptor positive MCF-7 cells (luminal). Cisplatin was applied at 2.5, 5, 10, and 20 μM, and cell viability and proliferation were measured using MTS and BrdU assays, respectively. The effect of cisplatin on the cellular hierarchy was examined by flow cytometry, immunofluorescence and qRT-PCR. Cisplatin treatment of 10 and 20 μM reduced cell viability by 36–51% and proliferation capacity by 36–67%. Treatment with cisplatin resulted in 12–67% down-regulation of stem cell markers (CD49f, SSEA4) and 10–130% up-regulation of differentiation markers (CK18, SMA, β-tubulin). At the mRNA level, CD49f was down-regulated whilst β-tubulin was up-regulated in the claudin-low cell lines. SSEA4 protein expression decreased upon cisplatin treatment, but SSEA4 mRNA expression increased indicating a differential regulation of cisplatin at the post-transcriptional level. It is concluded that cisplatin reduces breast cancer cell survival and induces differentiation of stem/progenitor cell subpopulations within breast cancer cell lines. These effects indicate the potential of this drug to target specific chemotherapy-resistant cells within a tumor. PMID:23761858

  16. Syndrome of Inappropriate Secretion of Antidiuretic Hormone Caused by Carboplatin After Switching from Cisplatin in a Metastatic Urethral Cancer Patient.

    PubMed

    Sugiyama, Yosuke; Naiki, Taku; Kondo, Masahiro; Iida, Keitaro; Kondo, Yuki; Tasaki, Yoshihiko; Kataoka, Tomoya; Hotta, Asami; Yasui, Takahiro; Kimura, Kazunori

    2017-05-01

    There is no established chemotherapy regimen in metastatic primary urethral cancer (mPUC). The efficacy of a cisplatin (CDDP)-based regimen has been reported, however, when the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) occurs, the chemotherapy regimen should be changed to another platinum compound. In this report, we describe a 66-year-old woman who was diagnosed as mPUC with, CDDP-induced SIADH. After switching her to CBDCA and careful managing her sodium balance, three courses of the chemotherapy regimen were completed.

  17. Efficacy and feasibility of docetaxel, cisplatin, and 5-fluorouracil induction chemotherapy for locally advanced head and neck squamous cell carcinoma classified as clinical nodal stage N2c, N3, or N2b with supraclavicular lymph node metastases.

    PubMed

    Izawa, Naoki; Onozawa, Yusuke; Hikosaka, Tomomi; Hamauchi, Satoshi; Tsushima, Takahiro; Todaka, Akiko; Machida, Nozomu; Haraguchi, Yutaka; Ogawa, Hirofumi; Nishimura, Tetsuo; Nakagawa, Masahiro; Fuke, Tomohito; Iida, Yoshiyuki; Kamijo, Tomoyuki; Onitsuka, Tetsuro; Boku, Narikazu; Yasui, Hirofumi; Yokota, Tomoya

    2015-06-01

    We evaluated the efficacy and feasibility of docetaxel, cisplatin, and 5-fluorouracil (TPF) induction chemotherapy followed by concurrent chemoradiotherapy (CRT) for locally advanced head and neck squamous cell carcinoma (HNSCC) with a high risk of distant metastases compared with CRT alone. We retrospectively analyzed 29 HNSCC patients with clinical nodal stage N2c, N3, or N2b disease and supraclavicular lymph node metastases receiving CRT alone (CRT group; n = 16) or TPF induction chemotherapy followed by CRT (TPF group; n = 13) between April 2008 and May 2012. The median follow-up periods were 14.5 (range 5.0-65.0) and 25.0 (range 14.0-32.0) months for CRT and TPF groups, respectively. A greater proportion of patient characteristics in the CRT group had advanced T and N stages. The overall response rate to induction TPF was 50.0%; grade 3-4 toxicities included neutropenia, febrile neutropenia, anorexia, and hyponatremia. Complete response rates after CRT completion were 55.5% in the TPF and 42.9% in the CRT group; median overall survival was not reached in the TPF group and was 14.0 months in the CRT group (p = 0.037). Multivariate analysis revealed that induction TPF and T stage were independent prognostic factors [hazard ratio (HR) = 0.196; 95% confidence interval (CI) 0.043-0.898; p = 0.036, HR = 9.966; 95% CI 2.270-43.75; p = 0.002, respectively). TPF followed by CRT is tolerated and may be an option for the treatment of locally advanced stage N2c, N3, or N2b HNSCC.

  18. A Retrospective, Multicenter Study of the Tolerance of Induction Chemotherapy With Docetaxel, Cisplatin, and 5-Fluorouracil Followed by Radiotherapy With Concomitant Cetuximab in 46 Cases of Squamous Cell Carcinoma of the Head and Neck

    SciTech Connect

    Buiret, Guillaume; Combe, Claire; Favrel, Veronique; Pommier, Pascal; Martin, Laurent; Ecochard, Rene; Fayette, Jerome; Tartas, Sophie; Ramade, Antoine; Ceruse, Philippe

    2010-06-01

    Purpose: To investigate, in a multicenter study, the tolerance of induction chemotherapy (ICT) and external radiotherapy (ERT) with concomitant cetuximab in the treatment of patients with squamous cell carcinoma of the head and neck (SCCHN). Patients and Methods: Clinical data from 46 patients with Stage III or IV nonmetastatic SCCHN who received docetaxel, cisplatin, and 5-fluorouracil as ICT, followed by ERT with concomitant cetuximab, were retrospectively analyzed. Clinical safety (weight, allergy, mucositis, and dermatitis) and paraclinical safety (levels of hemoglobin, polynuclear neutrophils, and creatinine clearance) were studied. The primary objective was the proportion of patients who completed the protocol. Results: The percentage of patients completing ICT was 73.9%, ERT 93.5%, and cetuximab 69.6%. Induction chemotherapy was better tolerated than that previously reported. The rates of temporary suspensions of radiation (39.1%, mean duration of 13 days) and hospitalization (26.1%) during ERT with concomitant cetuximab were high. Weight loss during treatment (21.4% of patients lost >10% of their body weight), radiodermatitis, and radiomucositis were the main causes of temporary suspension of treatment, although Grade 4 dermatitis was not experienced. There were no allergic reactions to cetuximab. Conclusion: The completed protocol rate for SCCHN patients receiving ICT and ERT with concomitant cetuximab is high and the toxicity acceptable. Future improvements to protocol will be possible through early action and systematic implementation of nutritional support coupled with antibiotic treatment upon the first signs of radiodermatitis. These data could be useful for prospective studies on the safety and efficacy of this protocol.

  19. In Silico Oncology: Quantification of the In Vivo Antitumor Efficacy of Cisplatin-Based Doublet Therapy in Non-Small Cell Lung Cancer (NSCLC) through a Multiscale Mechanistic Model

    PubMed Central

    Kolokotroni, Eleni; Dionysiou, Dimitra; Veith, Christian; Kim, Yoo-Jin; Franz, Astrid; Grgic, Aleksandar; Bohle, Rainer M.; Stamatakos, Georgios

    2016-01-01

    The 5-year survival of non-small cell lung cancer patients can be as low as 1% in advanced stages. For patients with resectable disease, the successful choice of preoperative chemotherapy is critical to eliminate micrometastasis and improve operability. In silico experimentations can suggest the optimal treatment protocol for each patient based on their own multiscale data. A determinant for reliable predictions is the a priori estimation of the drugs’ cytotoxic efficacy on cancer cells for a given treatment. In the present work a mechanistic model of cancer response to treatment is applied for the estimation of a plausible value range of the cell killing efficacy of various cisplatin-based doublet regimens. Among others, the model incorporates the cancer related mechanism of uncontrolled proliferation, population heterogeneity, hypoxia and treatment resistance. The methodology is based on the provision of tumor volumetric data at two time points, before and after or during treatment. It takes into account the effect of tumor microenvironment and cell repopulation on treatment outcome. A thorough sensitivity analysis based on one-factor-at-a-time and latin hypercube sampling/partial rank correlation coefficient approaches has established the volume growth rate and the growth fraction at diagnosis as key features for more accurate estimates. The methodology is applied on the retrospective data of thirteen patients with non-small cell lung cancer who received cisplatin in combination with gemcitabine, vinorelbine or docetaxel in the neoadjuvant context. The selection of model input values has been guided by a comprehensive literature survey on cancer-specific proliferation kinetics. The latin hypercube sampling has been recruited to compensate for patient-specific uncertainties. Concluding, the present work provides a quantitative framework for the estimation of the in-vivo cell-killing ability of various chemotherapies. Correlation studies of such estimates with

  20. Management of platinum-based chemotherapy-induced acute nausea and vomiting: is there a superior serotonin receptor antagonist?

    PubMed

    Hamadani, Mehdi; Chaudhary, Lubna; Awan, Farrukh T; Khan, Jawad K; Kojouri, Kiarash; Ozer, Howard; Tfayli, Arafat

    2007-06-01

    The last decade has witnessed the great impact of 5-hydroxytryptamine-3 receptor (5-HT(3))antagonists in revolutionizing the management of platinum-based chemotherapy-induced acute nausea and vomiting (CINV). However, despite the availability of a variety of 5-HT(3) antagonists, little data is published to support superiority of one drug over another, leaving the choice of serotonin receptor antagonist largely empirical. The National Comprehensive Cancer Network and American Society of Clinical Oncology guidelines for management of chemotherapy-associated nausea and vomiting cleary endorse the use of serotonin receptor antagonist; however, no single agent is preferred over the rest. Data for patients (n=159) receiving platinum-based chemotherapy regimens were retrospectively collected . Patients getting 5-HT(3) antagonists without steriods or those with known history of brain metastasis, gastroparesis, and intestinal obstruction were not eligible for the study. Patient characteristics including age, gender, primary diagnosis, history of heavy alcohol intake, chemotherapy regimen administered , number of cycles, and Eastern Cooperative Group performance status at the start of therapy were noted. Primary outcome was the complete control of platinum-induced acute nausea and vomiting. Secondary outcome measures included control of > or = grade 1 nausea or vomiting, comparison of two doses of dexamethasone, and antiemetic eficacy among various platinum drugs. National Cancer Institute Common Toxicity Criteria version 2.0 was used to assess toxicity. A total of 126 patients received 369 cycles of platinum-based therapy. Dolasetron ( n=157), granisetron ( n=81), and ondansetron ( n=131) achieved complete control of vomiting in 89.8, 95.5, and 92.3% (p=0.67) of cycles, respectively. Respectively, complete nausea control was observed in 68.1, 75.3 and, 69.4% (p=0.50). Dexamethasone 20 mg was not superior to 10 mg in complete control of nausea and vomiting ( p= 0.15 and p=0

  1. Paclitaxel plus cisplatin vs. 5-fluorouracil plus cisplatin as first-line treatment for patients with advanced squamous cell esophageal cancer

    PubMed Central

    Liu, Ying; Ren, Zhonghai; Yuan, Long; Xu, Shuning; Yao, Zhihua; Qiao, Lei; Li, Ke

    2016-01-01

    Paclitaxel plus cisplatin and 5-fluorouracil plus cisplatin treatments are effective strategies for patients with advanced esophageal squamous cell carcinoma. This study was to evaluate the safety and efficacy of paclitaxel plus cisplatin and 5-fluorouracil plus cisplatin as first-line chemotherapy for patients with advanced esophageal squamous cell carcinoma. A total of 398 patients with advanced esophageal squamous cell carcinoma who received chemotherapy were included and divided into 2 groups: paclitaxel plus cisplatin group and 5-fluorouracil plus cisplatin group. 195 patients received paclitaxel plus cisplatin and 203 patients received 5-fluorouracil plus cisplatin. The objective response rates were 42.5% and 38.4% for paclitaxel plus cisplatin group and 5-fluorouracil plus cisplatin group, respectively (P=0.948). The median progression-free survival was 7.85 months (95% CI, 6.77-8.94 months) for the paclitaxel plus cisplatin group and 6.53 months (95% CI, 5.63-7.43 months) for the 5-fluorouracil plus cisplatin group with significant difference (P=0.02). The median overall survival was 13.46 months (95% CI, 12.01-14.91 months) for the paclitaxel plus cisplatin group and 12.67 months (95% CI, 11.87-13.47 months) for the 5-fluorouracil plus cisplatin group (P=0.204). The first-line chemotherapy of paclitaxel plus cisplatin had better median progression-free survival than 5-fluorouracil plus cisplatin in patients with advanced esophageal squamous cell carcinoma with tolerable toxicities. PMID:27822423

  2. First-line combination chemotherapy with cisplatin, etoposide and ifosfamide for the treatment of disseminated germ cell cancer: re-evaluation in the granulocyte colony-stimulating factor era.

    PubMed

    Tanaka, Hajime; Yuasa, Takeshi; Fujii, Yasuhisa; Sakura, Mizuaki; Urakami, Shinji; Yamamoto, Shinya; Masuda, Hitoshi; Fukui, Iwao; Yonese, Junji

    2013-01-01

    This study re-evaluated the efficacy and tolerability of cisplatin, etoposide, and ifosfamide (VIP) combination chemotherapy as an alternative first-line regimen for patients with disseminated germ cell cancer (GCC) in this granulocyte colony-stimulating factor (G-CSF) era. The medical records of 91 consecutive patients with previously untreated disseminated GCC who received first-line VIP between 1995 and 2011 were retrospectively reviewed. The 5-year overall survival rates for patients with good (n = 49), intermediate (n = 22) and poor (n = 20) prognoses according to the International Germ Cell Cancer Collaborative Group classification were 100, 79 and 83%, respectively. G-CSF was given to all patients, and no treatment-related deaths due to myelosuppression occurred. The present study is the first to examine the therapeutic outcomes and safety profile of first-line VIP after routine G-CSF use. VIP might be an alternative first-line regimen for patients with disseminated GCC in this G-CSF era. © 2014 S. Karger AG, Basel

  3. Randomized Phase III Trial of Irinotecan Plus Cisplatin Compared With Paclitaxel Plus Carboplatin As First-Line Chemotherapy for Ovarian Clear Cell Carcinoma: JGOG3017/GCIG Trial.

    PubMed

    Sugiyama, Toru; Okamoto, Aikou; Enomoto, Takayuki; Hamano, Tetsutaro; Aotani, Eriko; Terao, Yasuhisa; Suzuki, Nao; Mikami, Mikio; Yaegashi, Nobuo; Kato, Kiyoko; Yoshikawa, Hiroyuki; Yokoyama, Yoshihito; Tanabe, Hiroshi; Nishino, Koji; Nomura, Hiroyuki; Kim, Jae-Weon; Kim, Byoung-Gie; Pignata, Sandro; Alexandre, Jerome; Green, John; Isonishi, Seiji; Terauchi, Fumitoshi; Fujiwara, Keiichi; Aoki, Daisuke

    2016-08-20

    Clear cell carcinoma (CCC) is a rare histologic subtype that demonstrates poor outcomes in epithelial ovarian cancer. The Japanese Gynecologic Oncology Group conducted the first randomized phase III, CCC-specific clinical trial that compared irinotecan and cisplatin (CPT-P) with paclitaxel plus carboplatin (TC) in patients with CCC. Six hundred sixty-seven patients with stage I to IV CCC of the ovary were randomly assigned to receive irinotecan 60 mg/m(2) on days 1, 8, and 15 plus cisplatin 60 mg/m(2) on day 1 (CPT-P group) every 4 weeks for six cycles or paclitaxel 175 mg/m(2) plus carboplatin area under the curve 6.0 mg/mL/min on day 1 every 3 weeks for six cycles (TC group). The primary end point was progression-free survival. Secondary end points were overall survival, overall response rate, and adverse events. Six hundred nineteen patients were clinically and pathologically eligible for evaluation. With a median follow-up of 44.3 months, 2-year progression-free survival rates were 73.0% in the CPT-P group and 77.6% in TC group (hazard ratio, 1.17; 95% CI, 0.87 to 1.58; P = .85). Two-year overall survival rates were 85.5% with CPT-P and 87.4% with TC (hazard ratio, 1.13; 95% CI, 0.80 to 1.61; one-sided P = .76). Grade 3/4 anorexia, diarrhea, nausea, vomiting, and febrile neutropenia occurred more frequently with CPT-P, whereas grade 3/4 leukopenia, neutropenia, thrombocytopenia, peripheral sensory neuropathy, and joint pain occurred more frequently with TC. No significant survival benefit was found for CPT-P. Both regimens were well tolerated, but the toxicity profiles differed significantly. Treatment with existing anticancer agents has limitations to improving the prognosis of CCC. © 2016 by American Society of Clinical Oncology.

  4. Optical molecular imaging approach for rapid assessment of response of individual cancer cells to chemotherapy

    NASA Astrophysics Data System (ADS)

    Luo, Zhen; Tikekar, Rohan Vijay; Samadzadeh, Kiana Michelle; Nitin, Nitin

    2012-10-01

    Predicting the response of individual patients to cytotoxic chemotherapy drugs is critical for developing individualized therapies. With this motivation, an optical molecular imaging approach was developed to detect cisplatin induced changes in the uptake and intracellular retention of choline. Intracellular uptake of choline was characterized using a click chemistry reaction between propargyl choline and Alexa-488 azide. Cisplatin induced changes in the uptake of propargyl choline in cells and tumor spheroids were compared with similar measurements using a fluorescent analogue of deoxyglucose and conventional cell viability assays. Uptake and intracellular retention of propargyl choline decreased with an increase in concentration of cisplatin. Intracellular uptake of propargyl choline was significantly reduced within 3 h of incubation with a sub-lethal dose of cisplatin. Results demonstrate that the imaging approach based on propargyl choline was more sensitive in detecting the early response of cancer cells to cisplatin as compared to the imaging based on fluorescent analogue of deoxyglucose and cell viability assays. Imaging measurements in tumor spheroids show a significant decrease in the uptake of propargyl choline following treatment with cisplatin. Overall, the results demonstrate a novel optical molecular imaging approach for rapid measurement of the response of individual cancer cells to cisplatin treatment.

  5. Mass Spectrometry Based Proteomics Study of Cisplatin-Induced DNA-Protein Cross-Linking in Human Fibrosarcoma (HT1080) Cells.

    PubMed

    Ming, Xun; Groehler, Arnold; Michaelson-Richie, Erin D; Villalta, Peter W; Campbell, Colin; Tretyakova, Natalia Y

    2017-04-17

    Platinum-based antitumor drugs such as 1,1,2,2-cis-diamminedichloroplatinum(II) (cisplatin), carboplatin, and oxaliplatin are currently used to treat nearly 50% of all cancer cases, and novel platinum based agents are under development. The antitumor effects of cisplatin and other platinum compounds are attributed to their ability to induce interstrand DNA-DNA cross-links, which are thought to inhibit tumor cell growth by blocking DNA replication and/or preventing transcription. However, platinum agents also induce significant numbers of unusually bulky and helix-distorting DNA-protein cross-links (DPCs), which are poorly characterized because of their unusual complexity. We and others have previously shown that DPCs block DNA replication and transcription and causes toxicity in human cells, potentially contributing to the biological effects of platinum agents. In the present work, we have undertaken a system-wide investigation of cisplatin-mediated DNA-protein cross-linking in human fibrosarcoma (HT1080) cells using mass spectrometry-based proteomics. DPCs were isolated from cisplatin-treated cells using a modified phenol/chloroform DNA extraction in the presence of protease inhibitors. Proteins were released from DNA strands and identified by mass spectrometry-based proteomics and immunological detection. Over 250 nuclear proteins captured on chromosomal DNA following treatment with cisplatin were identified, including high mobility group (HMG) proteins, histone proteins, and elongation factors. To reveal the exact molecular structures of cisplatin-mediated DPCs, isotope dilution HPLC-ESI(+)-MS/MS was employed to detect 1,1-cis-diammine-2-(5-amino-5-carboxypentyl)amino-2-(2'-deoxyguanosine-7-yl)-platinum(II) (dG-Pt-Lys) conjugates between the N7 guanine of DNA and the ε-amino group of lysine. Our results demonstrate that therapeutic levels of cisplatin induce a wide range of DPC lesions, which likely contribute to both target and off target effects of this

  6. Molecular mechanisms of cisplatin resistance in cervical cancer

    PubMed Central

    Zhu, Haiyan; Luo, Hui; Zhang, Wenwen; Shen, Zhaojun; Hu, Xiaoli; Zhu, Xueqiong

    2016-01-01

    Patients with advanced or recurrent cervical cancer have poor prognosis, and their 1-year survival is only 10%–20%. Chemotherapy is considered as the standard treatment for patients with advanced or recurrent cervical cancer, and cisplatin appears to treat the disease effectively. However, resistance to cisplatin may develop, thus substantially compromising the efficacy of cisplatin to treat advanced or recurrent cervical cancer. In this article, we systematically review the recent literature and summarize the recent advances in our understanding of the molecular mechanisms underlying cisplatin resistance in cervical cancer. PMID:27354763

  7. Gemcitabine plus split-dose cisplatin could be a promising alternative to gemcitabine plus carboplatin for cisplatin-unfit patients with advanced urothelial carcinoma.

    PubMed

    Kim, Yi Rang; Lee, Jae Lyun; You, Dalsan; Jeong, In Gab; Song, Cheryn; Hong, Bumsik; Hong, Jun Hyuk; Ahn, Hanjong

    2015-07-01

    Cisplatin-based chemotherapies are standard treatment regimens of advanced urothelial cell carcinoma. But a significant proportion of patients are unsuitable for cisplatin due to impaired renal function. Carboplatin-based regimens such as gemcitabine and carboplatin regimen (GCb) were applied due to less nephrotoxicity and side effects in these patients. However, it is known that clinical outcome of carboplatin-based regimens was unsatisfactory compared to cisplatin-based regimens. We compared the nephrotoxicity and response to treatment between GCb and gemcitabine plus split-dose cisplatin regimen (GC-S). GC-S consists of cisplatin 35 mg/m(2) given on day 1, 2 and gemcitabine 1000 mg/m(2) on day 1, 8 every 3 weeks. GCb consists of carboplatin (AUC 4.5) on day 1 and gemcitabine 1000 mg/m(2) on day 1, 8 every 3 weeks. Patient demographics, serum creatinine and calculated GFR, adverse events, and radiologic response were retrospectively reviewed. Forty-four patients with advanced urothelial carcinoma treated with GCb (n = 22) or GC-S (n = 22) in our institution. There was no difference at deterioration of serum creatinine or GFR between GCb and GC-S (p = 0.442, p = 0.345). For patients who had GFR < 60 mL/min/1.73 m(2) subgroup, similar results were produced (p = 0.292, p = 0.186). In addition, GC-S (68.4 %) showed improved response compared to GCb (31.6 %) (p = 0.023). Both treatments were well tolerated, and there were no unexpected serious adverse events. Based on preserved renal function, favorable response, and tolerability, GC-S could be a promising alternative to GCb for cisplatin-unfit patients with advanced urothelial carcinoma.

  8. Hepatitis B virus enhances cisplatin-induced hepatotoxicity via a mechanism involving suppression of glucose-regulated protein of 78 Kda.

    PubMed

    Zhang, Xiaoxue; Zhang, Rui; Yang, HuiOu; Xiang, Qian; Jiang, Qing; He, Qi; Zhang, Ting; Chen, Chen; Zhu, Huifen; Wang, Qiang; Ning, Qin; Li, Yiwu; Lei, Ping; Shen, Guanxin

    2016-07-25

    Cisplatin is a classical platinum-based chemotherapeutic drug used in the treatment of many cancer types, including hepatocellular carcinoma (HCC). The application of cisplatin is significantly limited by its toxicity, which may be affected by various biological factors. Persistence of Hepatitis B virus (HBV) infection leads to HCC development and may be associated with higher incidence of severe hepatitis during chemotherapy. However, whether HBV alters the susceptibility of hepatocytes to cisplatin remains poorly understood. Here, we demonstrate that HBV transfection enhanced cisplatin-induced hepatotoxicity via a mechanism involving suppression of glucose-regulated protein of 78 KDa (Grp78), a major stress-induced chaperone that localizes to the endoplasmic reticulum. Silencing Grp78 gene increased the susceptibility of HepG2 to cisplatin by activating caspase-3. Grp78 expression was down-regulated by HBV infection both in vitro and in liver tissues of patients. We compared the cisplatin sensitivity of hepatoma cells either expressing (HepG2.2.15 cells) or not expressing the entire Hepatitis B Virus genome (HepG2). HepG2.2.15 cells showed increased sensitivity to cisplatin and a higher apoptosis rate. Overexpression of Grp78 counteracted the increase of sensitivity of HepG2.215 cells to cisplatin. Furthermore, we found that HBV disrupted Grp78 synthesis in response to cisplatin stimulation, which may trigger severe and prolonged endoplasmic reticulum (ER) stress that can induce cellular apoptosis. Our findings provide new information into the effect of HBV in the modulation of Grp78 expression, and, consequently on cisplatin-induced hepatotoxicity during viral infection.

  9. Induction chemotherapy with paclitaxel and cisplatin followed by radiotherapy for larynx organ preservation in advanced laryngeal and hypopharyngeal cancer offers moderate late toxicity outcome (DeLOS-I-trial).

    PubMed

    Dietz, Andreas; Rudat, Volker; Dreyhaupt, Jens; Pritsch, Maria; Hoppe, Florian; Hagen, Rudolph; Pfreundner, Leo; Schröder, Ursula; Eckel, Hans; Hess, Markus; Schröder, Michael; Schneider, Petra; Jens, Bünzel; Zenner, Hans P; Werner, Jochen A; Engenhardt-Cabillic, Rita; Vanselow, Bernhard; Plinkert, Peter; Niewald, Marcus; Kuhnt, Thomas; Budach, Wilfried; Flentje, Michael

    2009-08-01

    A prospective multicenter phase-II trial (12 centers) was performed by the German larynx organ preservation group (DeLOS) to evaluate the effect of induction chemotherapy (ICHT) with paclitaxel/cisplatin (TP), followed by accelerated-hyperfractionated (concomitant boost) radiotherapy (RT) in responders. The trial was focused on larynx preservation, tumor control, survival, salvage surgery and late toxicity in patients with advanced larynx/hypopharynx carcinoma eligible for total laryngectomy (LE). Seventy-one patients (40 larynx, 87.5% St. III, IV; 31 hypopharynx, 93.4% St. III, IV) were enrolled into the study and treated with ICHT (200 mg/m(2) paclitaxel, 100 mg/m(2) cisplatin; day 1, 22) according to the DeLOS protocol. Patients with complete or partial tumor response proceeded to RT (69.9 Gy in 5.5 weeks). Non-responders received a LE followed by postoperative RT (56-70 Gy in 5.5-7 weeks). The response rate to ICHT for larynx cancer was 69.6% (7.1% complete, 62.5% partial response) and for hypopharyngeal cancer was 84.3% (6.9% complete, 77.4% partial response). Overall survival after 36 months was 60.3% (95% CI, 48.4-72.2%), after 42 months was 56.5% (95% CI, 44.2-68.8%). Laryngectomy-free survival was as follows: after 36 months, 43.0% (95% CI, 30.9-55.0%); after 42 months, 41.3% (95% CI, 29.3-53.3%). Both parameters did not show different outcomes after distinguishing larynx from hypopharynx. LE was indicated in 15 non-responders after ICHT. Five of the 15 non-responders refused the laryngectomy. Two of the five received RT instead and had no evidence of disease 42 months after RT. Late toxicity (dysphagia III, IV LENT SOMA score in laryngectomy-free survivors: after 6 months, 1.8%; 12 months, 11.4%; 18 months, 14.5%; 24 months, 8.1%; 36 months, 16%) and salvage surgery (4 pharyngocutaneous fistulas in 27 operations) were tolerable. In a large portion of patients eligible for LE, the larynx could be preserved with satisfying functional outcome. Good

  10. Induction chemotherapy in head and neck cancer patients followed by concomitant docetaxel-based radiochemotherapy.

    PubMed

    Mencoboni, M; Grillo-Ruggieri, F; Salami, A; Scasso, F; Rebella, L; Grimaldi, A; Dellepiane, M; Moratti, G; Bruzzone, A; Spigno, F; Ghio, R; Figliomeni, M

    2011-07-01

    Concurrent chemoradiotherapy has become the standard of care for patients with inoperable squamous cell head and neck carcinoma. More recently, induction chemotherapy has been adopted as an approach in the management of these patients. We report the results of a phase II trial associating induction chemotherapy and concomitant chemoradiotherapy in a series of patients with inoperable squamous cell head and neck cancer. Twenty-nine patients with advanced squamous cell carcinoma ineligible for surgery were enrolled. Induction chemotherapy with docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) every 21 days was administered for two cycles. Radiotherapy followed the induction phase. During radiotherapy, docetaxel was administered weekly at the dose of 33 mg/m(2) . Primary end point of the study was feasibility of treatment. Six (18%) patients failed to conclude the treatment schedule. Although response rates in evaluable patients were very high (disease control rate >90%), toxicities were a matter of concern. The reported treatment schedule proved infeasible. However, some modifications in ancillary therapies aimed at exploiting its efficacy could make it practicable.

  11. Sickness behavior induced by cisplatin chemotherapy and radiotherapy in a murine head and neck cancer model is associated with altered mitochondrial gene expression.

    PubMed

    Vichaya, Elisabeth G; Molkentine, Jessica M; Vermeer, Daniel W; Walker, Adam K; Feng, Rebekah; Holder, Gerard; Luu, Katherine; Mason, Ryan M; Saligan, Leo; Heijnen, Cobi J; Kavelaars, Annemieke; Mason, Kathy A; Lee, John H; Dantzer, Robert

    2016-01-15

    The present study was undertaken to explore the possible mechanisms of the behavioral alterations that develop in response to cancer and to cancer therapy. For this purpose we used a syngeneic heterotopic mouse model of human papilloma virus (HPV)-related head and neck cancer in which cancer therapy is curative. Mice implanted or not with HPV+ tumor cells were exposed to sham treatment or a regimen of cisplatin and radiotherapy (chemoradiation). Sickness was measured by body weight loss and reduced food intake. Motivation was measured by burrowing, a highly prevalent species specific behavior. Tumor-bearing mice showed a gradual decrease in burrowing over time and increased brain and liver inflammatory cytokine mRNA expression by 28 days post tumor implantation. Chemoradiation administered to healthy mice resulted in a mild decrease in burrowing, body weight, and food intake. Chemoradiation in tumor-bearing mice decreased tumor growth and abrogated liver and brain inflammation, but failed to attenuate burrowing deficits. PCR array analysis of selected hypoxia and mitochondrial genes revealed that both the tumor and chemoradiation altered the expression of genes involved in mitochondrial energy metabolism within the liver and brain and increased expression of genes related to HIF-1α signaling within the brain. The most prominent changes in brain mitochondrial genes were noted in tumor-bearing mice treated with chemoradiation. These findings indicate that targeting mitochondrial dysfunction following cancer and cancer therapy may be a strategy for prevention of cancer-related symptoms. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Interim (18)F-Fluorodeoxyglucose Positron Emission Tomography for Early Metabolic Assessment of Response to Cisplatin, Etoposide, and Bleomycin Chemotherapy for Metastatic Seminoma: Clinical Value and Future Directions.

    PubMed

    Necchi, Andrea; Nicolai, Nicola; Alessi, Alessandra; Miceli, Rosalba; Giannatempo, Patrizia; Raggi, Daniele; Tana, Silvia; Serafini, Gianluca; Padovano, Barbara; Mariani, Luigi; Crippa, Flavio; Salvioni, Roberto

    2016-06-01

    In patients with metastatic seminoma, designing a risk-adapted strategy that may help personalize the burden of treatment and follow-up is required. Patients who were administered cisplatin, etoposide, and bleomycin (PEB) were staged at baseline with computed tomography (CT), positron emission tomography (PET), and serum tumor markers. Restaging was then performed with PET after 2 cycles of PEB (PET2) and with CT after 3 to 4 cycles of treatment. The 20% cutoff of maximal standardized uptake value (SUVmax) changes and Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) criteria were applied to define the response. The Wilcoxon rank sum test was used to analyze the association between metabolic response and the shrinkage of target lesions. Between February 2009 and November 2013, 37 patients were enrolled. After 2 cycles of PEB, 27 patients (72.9%; 95% confidence interval [CI], 55.8-86.2) had a metabolic complete response (CR) and 10 patients had a partial response (PR; 27%; 95% CI, 13.8-44.1). A significant association was found between PET2 response and baseline (P = .003), final diameter (P < .001), and percentage of tumor shrinkage (P = .014) of target lesions. After 18 months' (interquartile range [IQR], 13-23) median follow-up, 2 patients with PET2 PR had relapsed disease; none of those with a CR had relapsed disease. A significant association was found between early metabolic response and tumor shrinkage in patients with advanced seminoma. Patients achieving a PET2 CR could be predicted not to need additional treatment after PEB, and simplifying their follow-up should be an end point. PET2 might also identify difficult to treat cases at an early stage. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. The method of GFR determination impacts the estimation of cisplatin eligibility in patients with advanced urothelial cancer.

    PubMed

    Horn, Thomas; Ladwein, Barbara; Maurer, Tobias; Redlin, Jutta; Seitz, Anna Katharina; Gschwend, Jürgen E; Retz, Margitta; Kübler, Hubert R

    2014-04-01

    To determine GFR with different methods in patients with first-line chemotherapy for advanced urothelial cancer (UC) and to evaluate the impact of these methods on the estimation of cisplatin eligibility. A database was built retrospectively containing all patients receiving first-line chemotherapy for UC between 2001 and 2012 in one German high-volume center. GFR was calculated with the methods by Cockcroft-Gault (CG), MDRD and CKD-EPI. Measurements of creatinine clearance with timed urine collections were registered. A total of 166 patients were included. All methods of renal function determination yielded consistent results in terms of cisplatin eligibility for 134 patients (80.7 %) and disagreeing results for 32 patients (19.3 %). Twenty-two of these 32 patients with borderline GFR received cisplatin-based chemotherapy. Fifteen of these 22 patients completed at least three cycles. The mean GFR in the mentioned 32 patients was 51.3, 56.2 and 54.2 ml/min with the method by CG, MDRD and CKD-EPI. Three, ten and four patients were estimated cisplatin-eligible with either method. There was a good correlation between MDRD and CKD-EPI (r (2) = 0.92). CG tended to underestimate GFR compared to both MDRD and CKD-EPI. Measurements of creatinine clearance showed a wide distribution in comparison with MDRD (r (2) = 0.002). The method used to determine GFR influences the estimation of cisplatin eligibility in a subset of UC patients. MDRD and CKD-EPI formulas seem most valuable, while CG tends to underestimate renal function. Using a strict cutoff of 60 ml/min may unnecessarily preclude cisplatin in some patients.

  14. Increased Sensitivity to Cisplatin in Non-Small Cell Lung Cancer Cell Lines after FHIT Gene Transfer1

    PubMed Central

    Andriani, F; Perego, P; Carenini, N; Sozzi, G; Roz, L

    2006-01-01

    Abstract To evaluate the relevance of fragile histidine triad (FHIT) status in relation to drug treatment, we analyzed the sensitivity of the Fhit-negative non-small cell lung cancer (NSCLC) cell line NCI-H460 to different drugs, after treatment with an adenoviral vector expressing the FHIT transgene. Expression of Fhit resulted in reduced sensitivity to etoposide, doxorubicin, and topotecan. This feature was associated with Fhit-induced downregulation of DNA topoisomerases I and II. In contrast, expression of Fhit did not modulate sensitivity to Taxol, but produced a slight increase in sensitivity to cisplatin, as shown by colony-forming assays. Analysis of apoptosis revealed that, after cisplatin exposure, the number of apoptotic cells was two-fold higher in Fhit-expressing H460 cells. Moreover, it appeared that wild-type p53 was required for sensitization to cisplatin because the effect was marginal in A549 and Calu-1 cells, where the p53 pathway is altered and simultaneous restoration of p53 and Fhit in Calu-1 cells increased cisplatin sensitivity. Fhit could also partially restore sensitivity to cisplatin in Bcl-2- and Bcl-xL-overexpressing H460 cells that are normally resistant to this drug. Our results support the possible relevance of FHIT in cisplatin-based chemotherapy as well as in the reversal of drug resistance in NSCLC. PMID:16533421

  15. Interventions for preventing neuropathy caused by cisplatin and related compounds.

    PubMed

    Albers, J; Chaudhry, V; Cavaletti, G; Donehower, R

    2007-01-24

    Cisplatin and several related antineoplastic agents used to treat many types of solid tumors are neurotoxic, and most patients completing a full course of cisplatin chemotherapy develop a clinically detectable sensory neuropathy. Effective neuroprotective therapies have been sought. To examine the efficacy of purported chemoprotective agents to prevent or limit the neurotoxicity of cisplatin and related agents among human patients. We searched the Cochrane Neuromuscular Disease Group Register (January 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1 2005), MEDLINE from (January 1966 to March 2005), EMBASE (from January 1980 to March 2005), LILACS (from January 1982 to March 2005), CINAHL (from January 1982 to March 2005) for randomized trials designed to evaluate neuroprotective agents used to prevent or limit neurotoxicity of cisplatin and related agents among human patients. Quasi-randomized or randomized controlled trials whose participants received cisplatin (or related compounds) chemotherapy with or without a potential neuroprotectant (amifostine, diethyldithiocarbamate, glutathione, Org 2766, or vitamin E) and were evaluated zero to six months after completing chemotherapy using quantitative sensory testing (primary) or other measures including nerve conduction studies or neurological impairment rating using validated scales (secondary). We identified 16 randomized trials involving five possible chemoprotective agents. Each study was reviewed by two authors who extracted the data and reached consensus. The included trials involved five unrelated treatments and included many disparate measures of neuropathy, resulting in insufficient data for any one measure to combine the results in most instances. The one of five eligible amifostine trials (541 participants) using quantitative sensory testing demonstrated a favorable outcome in terms of amifostine neuroprotection, but the subclinical result was based on 14

  16. Treatment of small cell lung cancer with TRA-8 in combination with cisplatin and radiation.

    PubMed

    Bonner, James A; Willey, Christopher D; Yang, Eddy S; Dobelbower, Michael C; Sanford, Leisa L; Bright, Sheila J; Buchsbaum, Donald J; Raisch, Kevin P

    2011-10-01

    Limited stage small cell lung cancer (SCLC) represents a minority of SCLC. Despite extensive clinical trials, standard treatment remains cisplatin-based chemotherapy and thoracic irradiation (TI). This study focused on the interaction of cisplatin/radiation with the anti-human DR5 monoclonal antibody TRA-8 in SCLC cells. TRA-8 binds specifically to DR5 and has been shown to activate apoptosis. Four human SCLC cell lines were utilized for experimentation (SCLC-41, SCLC-58, SCLC-68, and SCLC-74). Immunoblot analysis was used to determine relative protein levels of DR5, DR4 and pro-caspase 8 for each cell line. Using a tetrazolium-based assay (XTT), the IC(50) values for cisplatin with or without TRA-8 were determined for the SCLC cell lines. Four SCLC lines were assayed with a combination of TRA-8 (10 μg/ml), 2 Gy radiation and various concentrations of cisplatin. Apoptosis was evaluated using Annexin V-FITC and cleaved caspase immunoblotting. Using a SCLC-58 subcutaneous xenograft model, treatment began 21 d after tumor cell injection. Treatment included weekly cisplatin (4 mg/kg) and radiation of 1 Gy (24 h after cisplatin) and TRA-8 (200 μg) was administered i.p. twice weekly for three weeks. Immunoblot analysis showed similar levels of DR5 for all cell lines with variable levels of DR4. Various concentrations of TRA-8 antibody (≤ 10 μg/ml) induced no significant cytotoxicity in the SCLC cell lines. The in vitro combination treatment with TRA-8 (10 μg/ml), 1.25 μg/ml cisplatin and 2 Gy radiation showed increased cytotoxicity when compared to combinations without TRA-8. Furthermore, the triple combination demonstrated the greatest amount of apoptosis as measured by Annexin V staining. The in vivo studies showed the combination of 1G y, cisplatin and TRA-8 extended the tumor doubling time to 44 d as compared to any doublet treatment groups that ranged from 12 to 20 d. Analysis of survival data showed 100% of the combination group (RT+cisplatin+TRA-8) were

  17. New Insights into the Reactivity of Cisplatin with Free and Restrained Nucleophiles: Microsolvation Effects and Base Selectivity in Cisplatin-DNA Interactions.

    PubMed

    de Cózar, Abel; Larrañaga, Olatz; Bickelhaupt, F Matthias; San Sebastián, Eider; Ortega-Carrasco, Elisabeth; Maréchal, Jean-Didier; Lledós, Agustí; Cossío, Fernando P

    2016-12-05

    The reactivity of cisplatin towards different nucleophiles has been studied by using density functional theory (DFT). Water was considered first to analyze the factors that govern the transformation of cisplatin into more electrophilic aquated species by using an activation-strain model. It was found that the selectivity and reactivity of cisplatin is a delicate trade-off between strain and interaction energies and that the second chloride is a worse leaving group than the first. When similar studies were carried out with imidazole, guanine (G), and adenine (A), it was found that in general the second nucleophilic substitution reactions have lower activation barriers than the first ones. Finally, simulations of the structural restrictions imposed by the DNA scaffold in intra- and interstrand processes showed that the geometries of the reaction products are nonoptimal with respect to the unrestrained A and G nucleophiles, although the energetic cost is not considerable under physiological conditions, which thus permits nucleophilic substitution reactions that lead to highly distorted DNA. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Time-Series Modeling and Simulation for Comparative Cost-Effective Analysis in Cancer Chemotherapy: An Application to Platinum-Based Regimens for Advanced Non-small Cell Lung Cancer.

    PubMed

    Chisaki, Yugo; Nakamura, Nobuhiko; Yano, Yoshitaka

    2017-01-01

    The purpose of this study was to propose a time-series modeling and simulation (M&S) strategy for probabilistic cost-effective analysis in cancer chemotherapy using a Monte-Carlo method based on data available from the literature. The simulation included the cost for chemotherapy, for pharmaceutical care for adverse events (AEs) and other medical costs. As an application example, we describe the analysis for the comparison of four regimens, cisplatin plus irinotecan, carboplatin plus paclitaxel, cisplatin plus gemcitabine (GP), and cisplatin plus vinorelbine, for advanced non-small cell lung cancer. The factors, drug efficacy explained by overall survival or time to treatment failure, frequency and severity of AEs, utility value of AEs to determine QOL, the drugs' and other medical costs in Japan, were included in the model. The simulation was performed and quality adjusted life years (QALY) and incremental cost-effectiveness ratios (ICER) were calculated. An index, percentage of superiority (%SUP) which is the rate of the increased cost vs. QALY-gained plots within the area of positive QALY-gained and also below some threshold values of the ICER, was calculated as functions of threshold values of the ICER. An M&S process was developed, and for the simulation example, the GP regimen was the most cost-effective, in case of threshold values of the ICER=$70000/year, the %SUP for the GP are more than 50%. We developed an M&S process for probabilistic cost-effective analysis, this method would be useful for decision-making in choosing a cancer chemotherapy regimen in terms of pharmacoeconomic.

  19. Cisplatin impaired adipogenic differentiation of adipose mesenchymal stem cells.

    PubMed

    Chang, Yu-Hsun; Liu, Hwan-Wun; Chu, Tang-Yuan; Wen, Yao-Tseng; Ding, Dah-Ching

    2017-02-03

    Adipose mesenchymal stem cells (ASCs) were isolated from the adipose tissue and can be induced in vitro to differentiate into osteoblasts, chondroblasts, myocytes, neurons and other cell types. Cisplatin is a commonly used chemotherapy drug for cancer patients. However, the effects of cisplatin on ASC remain elusive. This study found that high-concentration cisplatin affects the viability of ASCs. First, IC50 concentration of cisplatin was evaluated. Proliferation of ASCs assessed by XTT method decreased immediately after cisplatin treatment with various concentrations. ASCs maintained mesenchymal stem cells surface markers evaluating by flow cytometry after cisplatin treatment. Upon differentiation by adding specific chemicals, a significant decrease in adipogenic differentiation (by Oil red staining) and osteogenic differentiation (by Alizarin red staining), and significant chondrogenic differentiation (by Alcian blue staining) were found after cisplatin treatment. Simultaneously, qRT-PCR was also used for evaluating the specific gene expressions after various differentiations. Finally, ASCs from one donor who had received cisplatin showed significantly decreased adipogenic differentiation but increased osteogenic differentiation compared with ASCs derived from one healthy donor. In conclusion, cisplatin affects the viability, proliferation, and differentiation of ASCs both in vitro and in vivo via certain signaling pathway such as p53 and Fas/FasL. The differentiation abilities of ASCs should be evaluated before their transplantation for repairing cisplatin-induced tissue damage.

  20. Nab-paclitaxel-based compared to docetaxel-based induction chemotherapy regimens for locally advanced squamous cell carcinoma of the head and neck

    PubMed Central

    Schell, Amy; Ley, Jessica; Wu, Ningying; Trinkaus, Kathryn; Wildes, Tanya Marya; Michel, Loren; Thorstad, Wade; Gay, Hiram; Lewis, James; Rich, Jason; Diaz, Jason; Paniello, Randal C; Nussenbaum, Brian; Adkins, Douglas R

    2015-01-01

    We previously reported that nab-paclitaxel-based induction chemotherapy (IC) and concurrent chemoradiotherapy resulted in low relapse rates (13%) and excellent survival in head and neck squamous cell carcinoma (HNSCC). We compare the disease-specific survival (DSS) and overall survival (OS) between patients given nab-paclitaxel, cisplatin, and fluorouracil with cetuximab (APF-C) and historical controls given docetaxel, cisplatin, and fluorouracil with cetuximab (TPF-C). Patients with locally advanced HNSCC were treated with APF-C (n = 30) or TPF-C (n = 38). After 3 cycles of IC, patients were scheduled to receive cisplatin concurrent with definitive radiotherapy. T and N classification and smoking history were similar between the two groups and within p16-positive and p16-negative subsets. The median duration of follow-up for living patients in the APF-C group was 43.5 (range: 30–58) months versus 52 (range: 13–84) months for TPF-C. The 2-year DSS for patients treated with APF-C was 96.7% [95% Confidence Interval (CI): 85.2%, 99.8%] and with TPF-C was 77.6% (CI: 62.6%, 89.7%) (P = 0.0004). Disease progression that resulted in death was more frequent in the TPF-C group (39%) compared with the APF-C group (3%) when adjusted for competing risks of death from other causes (Gray's test, P = 0.0004). In p16 positive OPSCC, the 2-year DSS for APF-C was 100% and for TPF-C was 74.6% (CI: 47.4%, 94.6%) (P = 0.0019) and the 2-year OS for APF-C was 94.1% (CI: 65.0%, 99.2%) and for TPF-C was 74.6% (CI: 39.8%, 91.1%) (P = 0.013). In p16 negative HNSCC, the 2-year DSS for APF-C was 91.7% (CI: 67.6%, 99.6%) and for TPF-C was 82.6% (CI: 64.4%, 94.8%) (P = 0.092). A 2-year DSS and OS were significantly better with a nab-paclitaxel-based IC regimen (APF-C) compared to a docetaxel-based IC regimen (TPF-C) in p16-positive OPSCC. PMID:25619559

  1. Relationship Between the DPD and TS mRNA Expression and the Response to S-1-Based Chemotherapy and Prognosis in Patients with Advanced Gastric Cancer.

    PubMed

    Shen, Xiao-Ming; Zhou, Chong; Lian, Lian; Li, Li-Qun; Li, Wei; Tao, Min

    2015-04-01

    The aim was to determine changes in dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) mRNAs in the blood of advanced gastric cancer (AGC) patients to see whether these enzymes affected the patients' response to S-1-based chemotherapy and prognosis. For this purpose, pretreatment DPD/TS mRNA expressions were determined in 40 AGC patients using RT-PCR. The patients were then administered with S-1-based regimen (S-1 + cisplatin) and toxicities were recorded. The relationship between the DPD/TS mRNA expressions and the chemotherapy response, drug resistance, and prognosis was analyzed. The data show that DPD mRNA expression correlated significantly with Lauren type while TS mRNA expression correlated with distant metastasis. Patients with higher DPD and/or TS mRNA expression(s) showed poor response, while those with low DPD mRNA expression showed better response to the chemotherapy. Pooled analysis showed that the patients with low DPD/TS mRNA expressions had better therapeutic response. The incidence of bone marrow suppression, diarrhea, and oral mucositis was high in patients with low DPD mRNA expression. Median overall survival (OS) in 40 patients was 13.5 months. It was 17 months for low and 10 months for high DPD (P = 0.044) and TS mRNA expression (P = 0.047). Pooled analysis showed that the patients with both low DPD/TS mRNA expressions had longer OS (P = 0.001). In conclusion, the detection of DPD and/or TS mRNA expression can be used to predict the response to S-1-based chemotherapy, drug resistance, and prognosis in AGC patients as well as to help guide the individualized treatment of gastric cancer.

  2. 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.

  3. French multicenter phase III randomized study testing concurrent twice-a-day radiotherapy and cisplatin/5-fluorouracil chemotherapy (BiRCF) in unresectable pharyngeal carcinoma: Results at 2 years (FNCLCC-GORTEC)

    SciTech Connect

    Bensadoun, Rene-Jean . E-mail: rene-jean.bensadoun@nice.fnclcc.fr; Benezery, Karen; Dassonville, Olivier; Magne, Nicolas; Poissonnet, Gilles; Ramaioli, Alain; Lemanski, Claire; Bourdin, Sylvain; Tortochaux, Jacques; Peyrade, Frederic; Marcy, Pierre-Yves; Chamorey, Emmanuel Phar; Vallicioni, Jacques; Seng Hang; Alzieu, Claude; Gery, Bernard; Chauvel, Pierre; Schneider, Maurice; Santini, Jose; Demard, Francois; Calais, Gilles

    2006-03-15

    Background: Unresectable carcinomas of the oropharynx and hypopharynx still have a poor long-term prognosis. Following a previous phase II study, this phase III multicenter trial was conducted between November 1997 and March 2002. Methods: Nontreated, strictly unresectable cases were eligible. Twice-daily radiation: two fractions of 1.2 Gy/day, 5 days per week, with no split (D1{sup {yields}}D46). Total tumor doses: 80.4 Gy/46 day (oropharynx), 75.6 Gy/44 day (hypopharynx). Chemotherapy (arm B): Cisplatin 100 mg/m{sup 2} (D1, D22, D43); 5FU, continuous infusion (D1{sup {yields}}D5), 750 mg/m{sup 2}/day cycle 1; 430 mg/m{sup 2}/day cycles 2 and 3. Results: A total of 163 evaluable patients. Grade 3-4 acute mucositis 82.6% arm B/69.5% arm A (NS); Grade 3-4 neutropenia 33.3% arm B/2.4% arm A (p < 0.05). Enteral nutrition through gastrostomy tube was more frequent in arm B before treatment and at 6 months (p < 0.01). At 24 months, overall survival (OS), disease-free survival (DFS), and specific survival (SS) were significantly better in arm B. OS: 37.8% arm B vs. 20.1% arm A (p = 0.038); DFS: 48.2% vs. 25.2% (p = 0.002); SS: 44.5% vs. 30.2% (p 0.021). No significant difference between the two arms in the amount of side effects at 1 and 2 years. Conclusion: For these unresectable cases, chemoradiation provides better outcome than radiation alone, even with an 'aggressive' dose-intensity radiotherapy schedule.

  4. Cisplatin: process and future.

    PubMed

    Stathopoulos, G P

    2013-01-01

    One of the most important anticancer agents is cisplatin (CDDP). Numerous studies with a CDDP-based combination have been reported over the last 30 years. The use of CDDP in the 1980s and 1990s showed responses in advanced stage non-small-cell lung cancer (NSCLC). Over the years it was found that the side effects of this agent (particularly nephrotoxicity) were a common problem. Agents such as carboplatin, taxanes, gemcitabine, irinotecan and pemetrexed proved to be effective in NSCLC with reduced or no nephrotoxicity. The administration of these newer agents improved several side effects, but without improving efficacy. When prophylactic (adjuvant) treatment for NSCLC was introduced, CDDP was the agent selected, which indicated the value of the drug. Recently, a novel formulation of CDDP, liposomal cisplatin, which has shown very low toxicity, no nephrotoxicity and equal effectiveness was produced; its importance is its higher effectiveness than standard CDDP in lung adenocarcinoma.

  5. [Combination chemotherapy with POMB/ACE (cisplatin, vincristine, methotrexate, bleomycin, actinomycin D, cyclophosphamide, etoposide) in advanced non-seminomatous testicular tumor].

    PubMed

    Masuda, F; Kawahara, M; Asano, K; Shirakawa, H

    1995-10-01

    Four cases with non-seminomatous testicular tumor in stage III completed chemotherapy with POMB/ACE. Of these 4 cases, metastasis to retroperitoneal lymph nodes was found in all of them. In addition, metastasis to the lung was noted in 3, and to the left supraclavicular lymph nodes in one. After orchiectomy, 5 courses of POMB/ACE therapy were given to each of the 4 cases. Tumor marker returned to normal value in all of the cases after 3-4 courses of treatment, with disappearance of metastasis to the lung and supraclavicular lymph nodes. However, the response rate in metastasis to retroperitoneal lymph nodes was CR in one case, and PR in 3. Therefore, retroperitoneal lymph nodes were excised in all 3 cases. Histologically, 2 of the 3 were found to have necrotic tissues. The remaining one patient had teratoma. An additional 1-3 courses of POMB/ACE therapy were given to these 3 cases. These 4 cases are alive without recurrence 6 years and 4 months, 5 years and 8 months, 4 years and 9 months, and 2 years 9 months, respectively, after orchiectomy. Thus POMB/ACE therapy is considered to be a useful method in the treatment of advanced testicular tumor.

  6. Biomaterial-based regional chemotherapy: Local anticancer drug delivery to enhance chemotherapy and minimize its side-effects.

    PubMed

    Krukiewicz, Katarzyna; Zak, Jerzy K

    2016-05-01

    Since the majority of anticancer pharmacological agents affect not only cancer tissue but also normal cells, chemotherapy is usually accompanied with severe side effects. Regional chemotherapy, as the alternative version of conventional treatment, leads to the enhancement of the therapeutic efficiency of anticancer drugs and, simultaneously, reduction of toxic effects to healthy tissues. This paper provides an insight into different approaches of local delivery of chemotherapeutics, such as the injection of anticancer agents directly into tumor tissue, the use of injectable in situ forming drug carriers or injectable platforms in a form of implants. The wide range of biomaterials used as reservoirs of anticancer drugs is described, i.e. poly(ethylene glycol) and its copolymers, polyurethanes, poly(lactic acid) and its copolymers, poly(ɛ-caprolactone), polyanhydrides, chitosan, cellulose, cyclodextrins, silk, conducting polymers, modified titanium surfaces, calcium phosphate based biomaterials, silicone and silica implants, as well as carbon nanotubes and graphene. To emphasize the applicability of regional chemotherapy in cancer treatment, the commercially available products approved by the relevant health agencies are presented.

  7. Resin-based Yttrium-90 microspheres for unresectable and failed first-line chemotherapy intrahepatic cholangiocarcinoma: preliminary results.

    PubMed

    Jia, Zhongzhi; Paz-Fumagalli, Ricardo; Frey, Gregory; Sella, David M; McKinney, J Mark; Wang, Weiping

    2017-03-01

    To evaluate the value of resin-based yttrium-90 ((90)Y) radioembolization for unresectable and failed first-line chemotherapy (cisplatin plus gemcitabine) intrahepatic cholangiocarcinoma (ICC). From February 2006 to September 2015, a retrospective study was conducted of all patients who underwent resin-based (90)Y therapy for unresectable and failed first-line chemotherapy ICC. Tumor response was assessed using modified RECIST criteria; side effects were assessed using Common Terminology Criteria for Adverse Events version 4.03; survivals were calculated from the date of diagnosis of ICC, beginning of first-line chemotherapy and first (90)Y procedure, respectively; effects of factors on survival were analyzed by Cox regression model. Twenty-four patients (eight male and 16 female) were included in this study. Mean 5.6 ± 1.6 cycles of first-line chemotherapy were performed prior to (90)Y treatment. The mean delivered activity of (90)Y was 1.6 ± 0.4 GBq with a total of 27 treatments. Disease control rate was 81.8% at 3 months after (90)Y therapy, with partial response (n = 8, 36.4%), stable disease (n = 10, 45.5%) and progressive disease (n = 6, 18.2%). CA199 changes pre- and 1 month post-treatment were complete (n = 2), partial (n = 2), none (n = 5) and progression (n = 2), respectively. Side effects included fatigue (n = 21, 87.5%), anorexia (n = 19, 79.2%), nausea (n = 15, 62.5%), abdominal pain (n = 10, 58.3%), vomiting (n = 4, 16.7%) and fever (n = 3, 12.5%). Radiation-induced gastrointestinal ulcer was identified in one patient. The mean follow-up was 11.3 ± 6.6 months, and the median survivals from the time of diagnosis of ICC, beginning of first-line chemotherapy and first (90)Y procedure were 24.0, 16.0 and 9.0 months, respectively, and the 6-, 12-, 18-, 24- and 30-month survival after (90)Y therapy were 69.9, 32.6, 27.2, 20.4 and 20.4%, respectively. ECOG performance status (P = 0.002) and lymph node metastases (P

  8. Protective Effect of Tempol against Cisplatin-Induced Ototoxicity.

    PubMed

    Youn, Cha Kyung; Kim, Jun; Jo, Eu-Ri; Oh, Jeonghyun; Do, Nam Yong; Cho, Sung Il

    2016-11-18

    One of the major adverse effects of cisplatin chemotherapy is hearing loss. Cisplatin-induced ototoxicity hampers treatment because it often necessitates dose reduction, which decreases cisplatin efficacy. This study was performed to investigate the effect of Tempol on cisplatin-induced ototoxicity in an auditory cell line, House Ear Institute-Organ of Corti 1 (HEI-OC1). Cultured HEI-OC1 cells were exposed to 30 μM cisplatin for 24 h with or without a 2 h pre-treatment with Tempol. Cell viability was determined using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and apoptotic cells were identified using terminal deoxynucleotidyl transferase dUTP nick end labeling of nuclei (TUNEL) assay and flow cytometry. The effects of Tempol on cisplatin-induced cleaved poly(ADP-ribose) polymerase, cleaved caspase, and mitochondrial inducible nitric oxide synthase expression were evaluated using western blot analysis. Levels of intracellular reactive oxygen species (ROS) were measured to assess the effects of Tempol on cisplatin-induced ROS accumulation. Mitochondria were evaluated by confocal microscopy, and the mitochondrial membrane potential was measured to investigate whether Tempol protected against cisplatin-induced mitochondrial dysfunction. Cisplatin treatment decreased cell viability, and increased apoptotic features and markers, ROS accumulation, and mitochondrial dysfunction. Tempol pre-treatment before cisplatin exposure significantly inhibited all these cisplatin-induced effects. These results demonstrate that Tempol inhibits cisplatin-induced cytotoxicity in HEI-OC1, and could play a preventive role against cisplatin-induced ototoxicity.

  9. Protective Effect of Tempol against Cisplatin-Induced Ototoxicity

    PubMed Central

    Youn, Cha Kyung; Kim, Jun; Jo, Eu-Ri; Oh, Jeonghyun; Do, Nam Yong; Cho, Sung Il

    2016-01-01

    One of the major adverse effects of cisplatin chemotherapy is hearing loss. Cisplatin-induced ototoxicity hampers treatment because it often necessitates dose reduction, which decreases cisplatin efficacy. This study was performed to investigate the effect of Tempol on cisplatin-induced ototoxicity in an auditory cell line, House Ear Institute-Organ of Corti 1 (HEI-OC1). Cultured HEI-OC1 cells were exposed to 30 μM cisplatin for 24 h with or without a 2 h pre-treatment with Tempol. Cell viability was determined using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and apoptotic cells were identified using terminal deoxynucleotidyl transferase dUTP nick end labeling of nuclei (TUNEL) assay and flow cytometry. The effects of Tempol on cisplatin-induced cleaved poly(ADP-ribose) polymerase, cleaved caspase, and mitochondrial inducible nitric oxide synthase expression were evaluated using western blot analysis. Levels of intracellular reactive oxygen species (ROS) were measured to assess the effects of Tempol on cisplatin-induced ROS accumulation. Mitochondria were evaluated by confocal microscopy, and the mitochondrial membrane potential was measured to investigate whether Tempol protected against cisplatin-induced mitochondrial dysfunction. Cisplatin treatment decreased cell viability, and increased apoptotic features and markers, ROS accumulation, and mitochondrial dysfunction. Tempol pre-treatment before cisplatin exposure significantly inhibited all these cisplatin-induced effects. These results demonstrate that Tempol inhibits cisplatin-induced cytotoxicity in HEI-OC1, and could play a preventive role against cisplatin-induced ototoxicity. PMID:27869744

  10. A New Rat Model of Cisplatin-induced Neuropathic Pain

    PubMed Central

    Lin, Hai; Heo, Bong Ha

    2015-01-01

    Background Chemotherapy-induced peripheral neuropathy is a major side effect of anti-cancer drugs, and our knowledge of its mechanisms is lacking. Several models for chemotherapy-induced neuropathy have been introduced. However, the outcomes of these models differ significantly among laboratories. Our object was to create a model of chemotherapy-induced neuropathy in rats with cancer. Methods Female Sprague-Dawley rats were used. Mammary rat metastasis tumor (MRMT-1) cells were implanted subcutaneously in rats. Chemotherapy-induced peripheral neuropathy was induced by injection of cisplatin once a day for four days. The responses to mechanical and thermal stimuli were examined using von Frey filaments, acetone, and radiant heat. Results Cisplatin (2 mg/kg/day) produced mechanical allodynia, while it did not induce cold allodynia or thermal hyperalgesia. This dose of cisplatin could work successfully against cancer. Body weight loss was not observed in cisplatin-treated rats, nor were other abnormal behaviors noted in the same rats. Conclusions Repeated injection of intraperitoneal cisplatin induced peripheral neuropathic pain in rats. Thus, this type of rat model has broad applicability in studies related to searching for the mechanism of cisplatin-induced mechanical allodynia and agents for the treatment of neuropathic pain. PMID:26495078

  11. Apelin-13 attenuates cisplatin-induced cardiotoxicity through inhibition of ROS-mediated DNA damage and regulation of MAPKs and AKT pathways.

    PubMed

    Zhang, Pu; Yi, Lu-Hua; Meng, Guang-Yuan; Zhang, Huan-Yi; Sun, Hai-Hui; Cui, Lian-Qun

    2017-05-01

    Platinum-based chemotherapy represents one of the most effective ways in combating human cancers. However, the cardiotoxicity subsequent severely limited its clinical application. Increased evidences indicate that oxidative stress plays a crucial role in the pathological process of platinum-induced cardiotoxicity. It is reported that apelin-13 a bioactive peptide has the scavenging capacity of free radical, and it has the potential to regulate the cardiovascular system. Hence, the potential of apelin-13 to antagonize cisplatin-induced cardiotoxicity was evaluated in H9c2 rat myocardial cells in vitro and in C57 mice in vivo. The results showed that cisplatin indeed caused DNA damage in H9c2 cells by promoting the accumulation of intracellular reactive oxygen species (ROS) and superoxide anion, which led to cell apoptosis and resulted in overt cardiotoxicity. However, apelin-13 pre-treatment effectively attenuated the cisplatin-induced ROS and superoxide anion generation, inhibited DNA damage, and suppressed the PARP cleavage and caspases activation. Further investigation revealed that apelin-13 blocked cisplatin-induced H9c2 cells apoptosis involving the regulation of MAPKs and PI3K/Akt signaling pathway. Importantly, apelin-13 co-treatment also significantly attenuated cisplatin-induced cardiotoxicity in vivo by inhibiting myocardial cells apoptosis and improving angiogenesis in mice heart. Taken together, our results suggest that the use of apelin-13 may be an effective strategy for antagonizing the cardiotoxicity-induced by platinum-based chemotherapy.

  12. Platinum-based neoadjuvant chemotherapy followed by radical surgery for cervical carcinoma international federation of gynecology and obstetrics stage IB2-IIB.

    PubMed

    Minig, Lucas; Colombo, Nicoletta; Zanagnolo, Vanna; Landoni, Fabio; Bocciolone, Luca; Cárdenas-Rebollo, José Miguel; Iodice, Simona; Maggioni, Angelo

    2013-11-01

    The objective of this study was to determine the response rate to chemotherapy, as well as the progression-free survival (PFS), the overall survival (OS), and the main prognostic factors in patients treated at the European Institute of Oncology in Milan, Italy. Retrospective data were collected on patients with uterine cervical carcinoma, International Federation of Gynecology and Obstetrics (FIGO) stage IB2 to IIB, who underwent platinum-based neoadjuvant chemotherapy (NACT) followed by radical hysterectomy. A total of 121 patients were studied. The median (range) age was 45 years old (23-69 years). The distribution of patients by International Federation of Gynecology and Obstetrics stage was as follows: n = 88 (73%) with stage IB2, n = 7 (6%) with stage IIA, and n = 26 (21%) with stage IIB. The median (range) tumor size was 50 mm (20-90 mm). Neoadjuvant chemotherapy involved a combination of cisplatin, paclitaxel, and ifosfamide in 80 patients (65%). Using this treatment, 112 patients (93%) received 3 cycles of NACT, whereas 6 (5%) received 4 cycles. Complete and partial pathology response was observed in 9 patients (7%) and 79 patients (66%), respectively. Adjuvant radiotherapy was not necessary in 65% of patients. A 5-year PFS and OS of 58% and 71%, respectively, were observed. Independent prognostic factors for PFS and OS were identified, including response to NACT, persistent lymph node metastases, and parametrial involvement. Neoadjuvant chemotherapy in this group of tumors is a promising treatment strategy and should be discussed with patients. Although these results are comparable to those obtained by standard chemoradiation treatment, one strategy should not be recommended over the other until the results of the ongoing phase 3 trial for NACT are released.

  13. Chemotherapy for advanced gastric cancer.

    PubMed

    Wagner, Anna Dorothea; Syn, Nicholas Lx; Moehler, Markus; Grothe, Wilfried; Yong, Wei Peng; Tai, Bee-Choo; Ho, Jingshan; Unverzagt, Susanne

    2017-08-29

    by adding a third drug to a two-drug regimen at the cost of increased toxicity, the comparison of regimens in which another chemotherapy was replaced by irinotecan was associated with a survival benefit (of borderline statistical significance), but without increased toxicity. For this reason irinotecan/5-FU-containing combinations are an attractive option for first-line treatment. Although they need to be interpreted with caution, subgroup analyses of one study suggest that elderly people have a greater benefit form oxaliplatin, as compared to cisplatin-based regimens, and that people with locally advanced disease or younger than 65 years might benefit more from a three-drug regimen including 5-FU, docetaxel, and oxaliplatin as compared to a two-drug combination of 5-FU and oxaliplatin, a hypothesis that needs further confirmation. For people with good performance status, the benefit of second-line chemotherapy has been established in several RCTs.

  14. Neoadjuvant and adjuvant chemotherapy approaches for invasive bladder cancer.

    PubMed

    Raghavan, Derek; Burgess, Earle; Gaston, Kris E; Haake, Michael R; Riggs, Steven B

    2012-10-01

    Deeply invasive bladder cancer, representing approximately 20% of incident cases, is cured by radical cystectomy or radiotherapy in less than 50% of cases. In an effort to improve cure rates, based on objective response rates in metastatic disease of 40%-70% from combination chemotherapy regimens, systemic chemotherapy has been incorporated into programs of definitive treatment for this disease. Several randomized trials and a meta-analysis have confirmed a survival benefit from neoadjuvant chemotherapy followed by definitive local treatment, reflecting both median survival figures and cure rates. Despite several promising phase II trials, no randomized trial of classical adjuvant chemotherapy for bladder cancer has demonstrated an overall survival benefit, despite increments in disease-free survival. Molecular prognostication has been studied in an effort to improve the utility of systemic therapy for invasive non-metastatic bladder cancer, but randomized trials have not shown associated survival benefit. Despite level 1 evidence of a survival benefit from neoadjuvant MVAC (methotrexate, vinblastine, doxorubicin [Adriamycin], cisplatin) or cisplatin, methotrexate, and vinblastine (CMV) chemotherapy, more than 50% of incident cases do not receive such treatment.

  15. Phase II trial of intraperitoneal cisplatin combined with intravenous paclitaxel in patients with ovarian, primary peritoneal and fallopian tube cancer.

    PubMed

    Landrum, Lisa M; Hyde, Johnny; Mannel, Robert S; McMeekin, D Scott; Moore, Kathleen N; Walker, Joan L

    2011-09-01

    BACKGROUND.: The objective of this study was to determine the toxicity of cisplatin-based intraperitoneal (IP)/intravenous (IV) treatment using a modified version of the IP/IV arm of GOG 172. METHODS.: Patients with stage IC-IV and recurrent ovarian cancer were treated with D1 paclitaxel (IV at 135 mg/m², 3-h infusion) and cisplatin (IP at 50 mg/m²) and D8 cisplatin (IP at 50 mg/m²) every 21 days for 6 cycles. The primary outcome measure was completion of 6 cycles. Toxicity was assessed using the CTCAE, v.3.0 as well as subjective reporting by patients after each cycle. RESULTS.: Twenty-one patients completed 87 cycles of chemotherapy with IP cisplatin and intravenous (IV) paclitaxel. Eleven patients (52%) were able to complete all 6 cycles. Reasons for failing to complete treatment: progression of disease (n=3), grade 3-4 ototoxicity (n=2), IP port complication (n=1), grade 4 fatigue (n=1), small bowel obstruction (n=1), severe paclitaxel reaction (n=1) and one patient refused further treatment (n=1). Dose reductions of paclitaxel (135 mg/m² to 110 mg/m²) were implemented per protocol for neutropenia (n=3) at a frequency of 3.75%. Dose delays were noted prior to 9 cycles for neutropenia (n=6), thrombocytopenia (n=1), elevated creatinine (n=1), and grade 3 rash (n=1) at a frequency of 10%. CONCLUSIONS.: Although only 52% of patients were able to complete 6 cycles of cisplatin-based IP chemotherapy, significant reductions in cisplatin-related metabolic toxicity and catheter-related complications were noted. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Nivolumab in Combination With Platinum-Based Doublet Chemotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer.

    PubMed

    Rizvi, Naiyer A; Hellmann, Matthew D; Brahmer, Julie R; Juergens, Rosalyn A; Borghaei, Hossein; Gettinger, Scott; Chow, Laura Q; Gerber, David E; Laurie, Scott A; Goldman, Jonathan W; Shepherd, Frances A; Chen, Allen C; Shen, Yun; Nathan, Faith E; Harbison, Christopher T; Antonia, Scott

    2016-09-01

    Nivolumab, a fully human immunoglobulin G4 programmed death-1 immune checkpoint inhibitor antibody, has demonstrated improved survival in previously treated patients with advanced non-small-cell lung cancer (NSCLC). CheckMate 012, a phase I, multicohort study, was conducted to explore the safety and efficacy of nivolumab as monotherapy or combined with current standard therapies in first-line advanced NSCLC. Here, we report results for nivolumab plus platinum-based doublet chemotherapy (PT-DC). Patients (N = 56) received nivolumab (intravenously) plus PT-DC concurrently every 3 weeks for four cycles followed by nivolumab alone until progression or unacceptable toxicity. Regimens were nivolumab 10 mg/kg plus gemcitabine-cisplatin (squamous) or pemetrexed-cisplatin (nonsquamous) or nivolumab 5 or 10 mg/kg plus paclitaxel-carboplatin (all histologies). The primary objective was to assess safety and tolerability. Secondary objectives included objective response rate and 24-week progression-free survival rate (per Response Evaluation Criteria in Solid Tumors version 1.1); exploratory objectives included overall survival (OS) and response by tumor programmed death ligand-1 expression. No dose-limiting toxicities occurred during the first 6 weeks of treatment. Forty-five percent of patients (25 of 56 patients) reported grade 3 or 4 treatment-related adverse events (AEs); 7% of patients (n = 4) had pneumonitis. Twenty-one percent of patients (n = 12) discontinued all study therapy as a result of treatment-related AEs. Objective response rates for nivolumab 10 mg/kg plus gemcitabine-cisplatin, nivolumab 10 mg/kg plus pemetrexed-cisplatin, nivolumab 10 mg/kg plus paclitaxel-carboplatin, and nivolumab 5 mg/kg plus paclitaxel-carboplatin were 33%, 47%, 47%, and 43%, respectively; 24-week progression-free survival rates were 51%, 71%, 38%, and 51%, respectively; 2-year OS rates were 25%, 33%, 27%, and 62%, respectively. Responses were achieved regardless of tumor programmed

  17. Factors Associated With Receipt of Breast Cancer Adjuvant Chemotherapy in a Diverse Population-Based Sample

    PubMed Central

    Griggs, Jennifer J.; Hawley, Sarah T.; Graff, John J.; Hamilton, Ann S.; Jagsi, Reshma; Janz, Nancy K.; Mujahid, Mahasin S.; Friese, Christopher R.; Salem, Barbara; Abrahamse, Paul H.; Katz, Steven J.

    2012-01-01

    Purpose Disparities in receipt of adjuvant chemotherapy may contribute to higher breast cancer fatality rates among black and Hispanic women compared with non-Hispanic whites. We investigated factors associated with receipt of chemotherapy in a diverse population-based sample. Patients and Methods Women diagnosed with breast cancer between August 2005 and May 2007 (N = 3,252) and reported to the Detroit, Michigan, or Los Angeles County Surveillance, Epidemiology, and End Results (SEER) registry were recruited to complete a survey. Multivariable analyses examined factors associated with chemotherapy receipt. Results The survey was sent to 3,133 patients; 2,290 completed a survey (73.1%), and 1,403 of these patients were included in the analytic sample. In multivariable models, disease characteristics were significantly associated with the likelihood of receiving chemotherapy. Low-acculturated Hispanics were more likely to receive chemotherapy than non-Hispanic whites (odds ratio [OR], 2.00; 95% CI, 1.31 to 3.04), as were high-acculturated Hispanics (OR, 1.43; 95% CI, 1.03 to 1.98). Black women were less likely to receive chemotherapy than non-Hispanic whites, but the difference was not significant (OR, 0.83; 95% CI, 0.64 to 1.08). Increasing age (even in women age < 50 years) and Medicaid insurance were associated with lower rates of chemotherapy receipt. Conclusion In this population-based sample, disease characteristics were strongly associated with receipt of chemotherapy, indicating that clinical benefit guides most treatment decisions. We found no compelling evidence that black women and Hispanics receive chemotherapy at lower rates. Interventions that address chemotherapy use rates according to age and insurance status may improve quality of systemic treatment. PMID:22869890

  18. The natural flavonoid apigenin sensitizes human CD44(+) prostate cancer stem cells to cisplatin therapy.

    PubMed

    Erdogan, Suat; Turkekul, Kader; Serttas, Rıza; Erdogan, Zeynep

    2017-04-01

    Prostate cancer (PCa) is the second most common type of cancer and the fifth leading cause of cancer-related death among men. Development of chemoresistance, tumor relapse and metastasis remain major barriers to effective treatment and all been identified to be associated with cancer stem cells (CSCs). Natural flavonoids such as apigenin have been shown to have the ability to improve the therapeutic efficacy of common chemotherapy agents through CSCs sensitization. Thus, the aim of this study was to evaluate the combination of apigenin with cisplatin on CD44(+) PCa stem cell growth and migration. Platinum-based anti-neoplastic drugs have been used to treat a number of malignancies including PCa. However, acquired resistance and side effects unfortunately have limited cisplatin's use. A CD44(+) subpopulation was isolated from human androgen-independent PC3 PCa cells by using human CD44-PE antibody. IC50 values were determined by MTT test. RT-qPCR, Western blot analyses and image-based cytometer were used to investigate apoptosis, cell cycle and their underlying molecular mechanisms. Cell migration was evaluated by wound healing test. The combination of the IC50 doses of apigenin (15μM) and cisplatin (7.5μM) for 48h significantly enhanced cisplatin's cytotoxic and apoptotic effects through downregulation of Bcl-2, sharpin and survivin; and upregulation of caspase-8, Apaf-1 and p53 mRNA expression. The combined therapy suppressed the phosphorylation of p-PI3K and p-Akt, inhibited the protein expression of NF-κB, and downregulated the cell cycle by upregulating p21, as well as cyclin dependent kinases CDK-2, -4, and -6. Apigenin significantly increased the inhibitory effects of cisplatin on cell migration via downregulation of Snail expression. In conclusion, our study showed the possible therapeutic approach of using apigenin to potentially increase the effects of cisplatin by targeting CSCs subset in prostate cancer.

  19. Role of autophagy in cisplatin-induced ototoxicity.

    PubMed

    Youn, Cha Kyung; Kim, Jun; Park, Jun-Hee; Do, Nam Yong; Cho, Sung Il

    2015-11-01

    Hearing loss is a major side effect of cisplatin chemotherapy. Although cell death in cisplatin-induced ototoxicity is primarily caused by apoptosis, the exact mechanism behind the ototoxic effects of cisplatin is not fully understood. Autophagy is generally known as a pro-survival mechanism that protects cells under starvation or stress conditions. However, recent research has reported that autophagy plays a functional role in cell death also. This study aimed to investigate the role of autophagy in cisplatin-induced ototoxicity in an auditory cell line. Cultured HEI-OC1 cells were exposed to 30 μM cisplatin for 48 h, and cell viability was tested using MTT assays. To evaluate whether autophagy serves to cell death after cisplatin exposure, western blotting and immunofluorescence staining for LC3-II were performed. Markers of two autophagy-related pathways, mTOR and class III PI3K, were also investigated. The formation of the autophagic protein LC3-II in response to 30 μM cisplatin increased with time. The early upregulation of autophagy exerted cytoprotective activity via the class III PI3K pathway. But later increase in autophagy induced cell death by suppressing the mTOR pathway. Our results prove that autophagy could induce cell death during cisplatin-induced ototoxicity, and modulating the autophagic pathway might be another strategy against cisplatin-induced ototoxicity. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Histone H4 expression is cooperatively maintained by IKKβ and Akt1 which attenuates cisplatin-induced apoptosis through the DNA-PK/RIP1/IAPs signaling cascade

    PubMed Central

    Wang, Ruixue; Zheng, Xuelian; Zhang, Lei; Zhou, Bin; Hu, Huaizhong; Li, Zhiping; Zhang, Lin; Lin, Yong; Wang, Xia

    2017-01-01

    While chromatin remodeling mediated by post-translational modification of histone is extensively studied in carcinogenesis and cancer cell’s response to chemotherapy and radiotherapy, little is known about the role of histone expression in chemoresistance. Here we report a novel chemoresistance mechanism involving histone H4 expression. Extended from our previous studies showing that concurrent blockage of the NF-κB and Akt signaling pathways sensitizes lung cancer cells to cisplatin-induced apoptosis, we for the first time found that knockdown of Akt1 and the NF-κB-activating kinase IKKβ cooperatively downregulated histone H4 expression, which increased cisplatin-induced apoptosis in lung cancer cells. The enhanced cisplatin cytotoxicity in histone H4 knockdown cells was associated with proteasomal degradation of RIP1, accumulation of cellular ROS and degradation of IAPs (cIAP1 and XIAP). The cisplatin-induced DNA-PK activation was suppressed in histone H4 knockdown cells, and inhibiting DNA-PK reduced expression of RIP1 and IAPs in cisplatin-treated cells. These results establish a novel mechanism by which NF-κB and Akt contribute to chemoresistance involving a signaling pathway consisting of histone H4, DNA-PK, RIP1 and IAPs that attenuates ROS-mediated apoptosis, and targeting this pathway may improve the anticancer efficacy of platinum-based chemotherapy. PMID:28139737

  1. A phase 2 randomized study of TAS-102 versus topotecan or amrubicin in patients requiring second-line chemotherapy for small cell lung cancer refractory or sensitive to frontline platinum-based chemotherapy.

    PubMed

    Scagliotti, Giorgio; Nishio, Makoto; Satouchi, Miyako; Valmadre, Giuseppe; Niho, Seiji; Galetta, Domenico; Cortinovis, Diego; Benedetti, Fabio; Yoshihara, Eiji; Makris, Lukas; Inoue, Akira; Kubota, Kaoru

    2016-10-01

    TAS-102 is an oral combination treatment comprised of an antimetabolite, trifluridine, a thymidine-based nucleoside analog, and tipiracil hydrochloride, at a molar ratio of 1:0.5. This antimetabolite has demonstrated efficacy in clinical trials, including a global phase 3 trial in metastatic colorectal cancer. As this agent has shown activity greater than cisplatin in small cell lung cancer xenograft mouse models, the objective of this study was to evaluate TAS-102 in the second-line treatment of small cell lung cancer. This was a multicenter, open-label, two-arm, randomized phase 2 study designed to compare oral TAS-102 (35mg/m(2)/dose twice daily) versus control (topotecan or amrubicin). Patients requiring second-line chemotherapy for treatment of small cell lung cancer, either refractory or sensitive to frontline platinum-based chemotherapy, were enrolled. Eighteen patients were enrolled. Eight of nine patients receiving TAS-102 discontinued treatment due to progressive disease and one patient died due to clinical progression during the safety follow-up. Unplanned interim futility considerations were made, and the study was terminated early because it was unlikely that superiority of TAS-102 versus comparator could be demonstrated. Six control patients discontinued therapy due to progressive disease and one due to an adverse event. Median progression-free survival was 1.4 months (range 0.9-1.8) versus 2.7 months (range 1.0-6.8) for TAS-102 and control, respectively, with a hazard ratio of 3.76 (80% CI, 1.68-8.40) favoring control. The most common adverse events with TAS-102 were neutropenia, diarrhea, anemia, anorexia, and fatigue, each in three patients. TAS-102 showed no evidence of activity in second-line small cell lung cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Identification of small molecule inhibitors of ERCC1-XPF that inhibit DNA repair and potentiate cisplatin efficacy in cancer cells

    PubMed Central

    Arora, Sanjeevani; Heyza, Joshua; Zhang, Hao; Kalman-Maltese, Vivian; Tillison, Kristin; Floyd, Ashley M.; Chalfin, Elaine M.; Bepler, Gerold; Patrick, Steve M.

    2016-01-01

    ERCC1-XPF heterodimer is a 5′-3′ structure-specific endonuclease which is essential in multiple DNA repair pathways in mammalian cells. ERCC1-XPF (ERCC1-ERCC4) repairs cisplatin-DNA intrastrand adducts and interstrand crosslinks and its specific inhibition has been shown to enhance cisplatin cytotoxicity in cancer cells. In this study, we describe a high throughput screen (HTS) used to identify small molecules that inhibit the endonuclease activity of ERCC1-XPF. Primary screens identified two compounds that inhibit ERCC1-XPF activity in the nanomolar range. These compounds were validated in secondary screens against two other non-related endonucleases to ensure specificity. Results from these screens were validated using an in vitro gel-based nuclease assay. Electrophoretic mobility shift assays (EMSAs) further show that these compounds do not inhibit the binding of purified ERCC1-XPF to DNA. Next, in lung cancer cells these compounds potentiated cisplatin cytotoxicity and inhibited DNA repair. Structure activity relationship (SAR) studies identified related compounds for one of the original Hits, which also potentiated cisplatin cytotoxicity in cancer cells. Excitingly, dosing with NSC16168 compound potentiated cisplatin antitumor activity in a lung cancer xenograft model. Further development of ERCC1-XPF DNA repair inhibitors is expected to sensitize cancer cells to DNA damage-based chemotherapy. PMID:27650543

  3. Identification of small molecule inhibitors of ERCC1-XPF that inhibit DNA repair and potentiate cisplatin efficacy in cancer cells.

    PubMed

    Arora, Sanjeevani; Heyza, Joshua; Zhang, Hao; Kalman-Maltese, Vivian; Tillison, Kristin; Floyd, Ashley M; Chalfin, Elaine M; Bepler, Gerold; Patrick, Steve M

    2016-11-15

    ERCC1-XPF heterodimer is a 5'-3' structure-specific endonuclease which is essential in multiple DNA repair pathways in mammalian cells. ERCC1-XPF (ERCC1-ERCC4) repairs cisplatin-DNA intrastrand adducts and interstrand crosslinks and its specific inhibition has been shown to enhance cisplatin cytotoxicity in cancer cells. In this study, we describe a high throughput screen (HTS) used to identify small molecules that inhibit the endonuclease activity of ERCC1-XPF. Primary screens identified two compounds that inhibit ERCC1-XPF activity in the nanomolar range. These compounds were validated in secondary screens against two other non-related endonucleases to ensure specificity. Results from these screens were validated using an in vitro gel-based nuclease assay. Electrophoretic mobility shift assays (EMSAs) further show that these compounds do not inhibit the binding of purified ERCC1-XPF to DNA. Next, in lung cancer cells these compounds potentiated cisplatin cytotoxicity and inhibited DNA repair. Structure activity relationship (SAR) studies identified related compounds for one of the original Hits, which also potentiated cisplatin cytotoxicity in cancer cells. Excitingly, dosing with NSC16168 compound potentiated cisplatin antitumor activity in a lung cancer xenograft model. Further development of ERCC1-XPF DNA repair inhibitors is expected to sensitize cancer cells to DNA damage-based chemotherapy.

  4. Incidence of hand-foot syndrome with capecitabine in combination with chemotherapy as first-line treatment in patients with advanced and/or metastatic gastric cancer suitable for treatment with a fluoropyrimidine-based regimen.

    PubMed

    Gómez-Martin, Carlos; Sánchez, Antonio; Irigoyen, Antonio; Llorente, Beatriz; Pérez, Begoña; Serrano, Raquel; Safont, M José; Falcó, Esther; Lacasta, Adelaida; Reboredo, Margarita; Aparicio, Jorge; Dueñas, Rosario; Muñoz, Marta Llanos; Regueiro, Pilar; Sanchez-Viñes, Elena; López, Rafael López

    2012-09-01

    Hand-foot syndrome (HFS) is a limiting toxicity of capecitabine, which is not life-threatening but could compromise capecitabine efficacy. This phase II, multicenter, non-controlled study assessed the safety, particularly grade three HFS incidence, and efficacy of four capecitabine-based chemotherapy regimens [cisplatin/capecitabine (CX), epirubicin/cisplatin/capecitabine (ECX), epirubicin/oxaliplatin/capecitabine (EOX) and docetaxel/cisplatin/capecitabine (DCX)] as first-line treatment for advanced and/or metastatic gastric cancer. One hundred and eight patients were assigned to one of the four treatment groups, according to investigator's criteria, and grouped together for both safety and efficacy primary analyses. HFS was reported in 31 patients (19.6%) and its first presentation occurred at a median of 72 days (range 19-209 days). Grade 3 HFS developed in 6.3, 5.2, 3.7 and 2.4%, of patients receiving ECX, DCX, EOX or CX chemotherapy regimen, respectively. Capecitabine dose reduction/discontinuation due to HFS was required in 5.7% of patients (9/158). The most common (> 10%) grade 3-4 treatment-related AEs were neutropenia (15.2%), asthenia (12.0%) and diarrhoea (11.4%). A moderate incidence of HFS was reported in patients treated with capecitabine, which generally presented late and required dose reduction in < 1/3 of patients. The results suggest that capecitabine may be useful in combination with standard fluorouracil-based regimens in patients with advanced and/or metastatic gastric cancer with favourable safety profile.

  5. Reduced ghrelin secretion in the hypothalamus of rats due to cisplatin-induced anorexia.

    PubMed

    Yakabi, Koji; Sadakane, Chiharu; Noguchi, Masamichi; Ohno, Shino; Ro, Shoki; Chinen, Katsuya; Aoyama, Toru; Sakurada, Tomoya; Takabayashi, Hideaki; Hattori, Tomohisa

    2010-08-01

    Although chemotherapy with cisplatin is a widely used and effective cancer treatment, the undesirable gastrointestinal side effects associated with it, such as nausea, vomiting, and anorexia, markedly decrease patients' quality of life. To elucidate the mechanism underlying chemotherapy-induced anorexia, focusing on the hypothalamic ghrelin secretion-anorexia association, we measured hypothalamic ghrelin secretion in fasted and cisplatin-treated rats. Hypothalamic ghrelin secretion changes after vagotomy or administration of cisplatin. Cisplatin + rikkunshito, a serotonin 2C receptor antagonist or serotonin 3 receptor antagonist, was investigated. The effects of intracerebroventricular (icv) administration of ghrelin or the serotonin 2C receptor antagonist SB242084 on food intake were also evaluated in cisplatin-treated rats. Hypothalamic ghrelin secretion significantly increased in 24-h-fasted rats compared to freely fed rats and was markedly reduced 24 and 48 h after cisplatin treatment in cisplatin-treated rats compared to saline-treated rats, although their plasma ghrelin levels were comparable. In cisplatin-treated rats, icv ghrelin administration reversed the decrease in food intake, vagotomy partially restored hypothalamic ghrelin secretion, and hypothalamic serotonin 2C receptor mRNA expression increased significantly. Administration of rikkunshito (an endogenous ghrelin enhancer) or a serotonin 2C receptor antagonist reversed the decrease in hypothalamic ghrelin secretion and food intake 24 h after cisplatin treatment. Cisplatin-induced anorexia is mediated through reduced hypothalamic ghrelin secretion. Cerebral serotonin 2C receptor activation partially induces decrease in hypothalamic ghrelin secretion, and rikkunshito suppresses cisplatin-induced anorexia by enhancing this secretion.

  6. Reinforcement learning-based control of drug dosing for cancer chemotherapy treatment.

    PubMed

    Padmanabhan, Regina; Meskin, Nader; Haddad, Wassim M

    2017-08-16

    The increasing threat of cancer to human life and the improvement in survival rate of this disease due to effective treatment has promoted research in various related fields. This research has shaped clinical trials and emphasized the necessity to properly schedule cancer chemotherapy to ensure effective and safe treatment. Most of the control methodologies proposed for cancer chemotherapy scheduling treatment are model-based. In this paper, a reinforcement learning (RL)-based, model-free method is proposed for the closed-loop control of cancer chemotherapy drug dosing. Specifically, the Q-learning algorithm is used to develop an optimal controller for cancer chemotherapy drug dosing. Numerical examples are presented using simulated patients to illustrate the performance of the proposed RL-based controller. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. eIF4E promotes tumorigenesis and modulates chemosensitivity to cisplatin in esophageal squamous cell carcinoma

    PubMed Central

    Zhao, Hui; Deng, Juan; Long, Ying; Shuai, Meng-ting; Li, Qian; Gu, Huan; Chen, Ya-qi; Leng, Ai-min

    2016-01-01

    Patients with esophageal squamous cell cancer are often diagnosed with advanced diseases that respond poorly to chemotherapy. Overexpression of eIF4E leads to enhance the translation of key malignancy-related proteins and enabling tumor growth and chemoresistance in a variety of human malignancies, but whether it has a role in ESCC remains obscure. We hypothesized that eIF4E promoted ESCC tumorigenesis and facilitated the development of acquired resistance to the cisplatin-based chemotherapy. In this study, we showed that eIF4E expression was increased significantly in clinical ESCC tissues and and ESCC cell lines and its expression level was correlated with lymph node metastasis, TNM stage, as well as overall and disease-free survival of ESCC. We also showed here that knockdown of eIF4E in EC9706 would dramatically reduced cell proliferation, colony formation, migration and invasion, apoptosis in vitro as well as in vivo, and vice versa. Moreover, “weak mRNAs” were demonstrated to be regulated by eIF4E in ESCC, which might interpret the above function. Overexpression of eIF4E decreased the efficacy of cisplatin-induced cell growth inhibition in ESCC cell line and xenograft model (P < 0.05). eIF4E knockdown by shRNA increased cisplatin-induced cytotoxicity in ESCC cell lines, and enhanced chemosensitivity to cisplatin in xenograft tumor models. Furthermore, we found that the PI3K/AKT pathway and Bcl-2/Bax ratio might be responsible for the eIF4E-induced cisplatin resistance in ESCC. Our data collectively show association of eIF4E expression with chemotherapeutic response in ESCC, and suggest that therapeutically targeting eIF4E may be a viable means of improving chemotherapy response in ESCC. PMID:27588477

  8. Transcriptome Sequencing Reveals Key Pathways and Genes Associated with Cisplatin Resistance in Lung Adenocarcinoma A549 Cells

    PubMed Central

    Fang, Yani; Zhang, Cheng; Wu, Tong; Wang, Qi; Liu, Jinhui; Dai, Penggao

    2017-01-01

    Acquired resistance to cisplatin-based chemotherapy frequently occurs in patients with non-small cell lung cancer, and the underlying molecular mechanisms are not well understood. The aim of this study was to investigate whether a distinct gene expression pattern is associated with acquired resistance to cisplatin in human lung adenocarcinoma. Whole-transcriptome sequencing was performed to compare the genome-wide gene expression patterns of the human lung adenocarcinoma A549 cisplatin-resistant cell line A549/DDP with those of its progenitor cell line A549. A total of 1214 differentially expressed genes (DEGs) were identified, 656 of which were upregulated and 558 were downregulated. Functional annotation of the DEGs in the Kyoto Encyclopedia of Genes and Genomes database revealed that most of the identified genes were enriched in the PI3K/AKT, mitogen-activated protein kinase, actin cytoskeleton regulation, and focal adhesion pathways in A549/DDP cells. These results support previous studies demonstrating that the pathways regulating cell proliferation and invasion confer resistance to chemotherapy. Furthermore, the results proved that cell adhesion and cytoskeleton regulation is associated with cisplatin resistance in human lung cancer. Our study provides new promising biomarkers for lung cancer prognosis and potential therapeutic targets for lung cancer treatment. PMID:28114404

  9. Analysis of risk factors for cisplatin-induced ototoxicity in patients with testicular cancer.

    PubMed Central

    Bokemeyer, C.; Berger, C. C.; Hartmann, J. T.; Kollmannsberger, C.; Schmoll, H. J.; Kuczyk, M. A.; Kanz, L.

    1998-01-01

    This study evaluates the degree and relevance of persisting ototoxicity after cisplatin-based standard-dose chemotherapy for testicular cancer, with emphasis on identification of potential factors for an increased risk of this late sequel. Hearing thresholds of 86 patients with a median age of 31 years (range 21-53 years) and a median follow-up time of 58 months (range 15-159 months) were assessed by conventional pure-tone audiometry. Interviews were conducted evaluating the patients' history with special regard to audiological risk factors, as well as circumstances of ototoxic symptoms. Details concerning treatment and patient variables were extracted retrospectively from the patients' charts. An additional screening programme assessed current body functions, blood parameters and other late toxicities. Symptomatic ototoxicity persisted in 20% of patients (59% tinnitus, 18% hearing loss, 23% both), while 10% had experienced completely reversible ototoxic symptoms for a duration of 1-18 months after treatment. Symptoms were bilateral in 81% of patients. Hearing thresholds were compatible with cisplatin-induced hearing loss in 42% of audiograms performed. Subjective (history) and objective (audiogram) findings were not always consistent. The following statistically significant risk factors for ototoxicity were established: high cumulative dose of cisplatin (P < 0.0001); history of noise exposure (P = 0.006). Additionally, high doses of vincristine (P = 0.001) seemed to result in reversible ototoxic symptoms. No other independent risk factors were identified. In conclusion, persisting ototoxicity represents a clinical sequel for approximately 20% of testicular cancer patients treated at standard dose but may affect more than 50% of patients receiving cumulative doses of cisplatin > 400 mg m(-2). Previous noise exposure may also result in a threefold increased risk for cisplatin ototoxicity. Future studies should use these risk factors as important stratification

  10. Structure Determination of Ornithine-Linked Cisplatin by Infrared Multiple Photon Dissociation Action Spectroscopy

    NASA Astrophysics Data System (ADS)

    He, Chenchen; Kimutai, Bett; Hamlow, Lucas; Roy, Harrison; Nei, Y.-W.; Bao, Xun; Gao, Juehan; Martens, Jonathan K.; Berden, Giel; Oomens, Jos; Maitre, Philippe; Steinmetz, Vincent; McNary, Christopher P.; Armentrout, Peter B.; Chow, C. S.; Rodgers, M. T.

    2016-06-01

    Cisplatin [(NH_3)_2PtCl_2], the first FDA-approved platinum-based anticancer drug, has been widely used in cancer chemotherapy. Its pharmacological mechanism has been identified as its ability to coordinate to genomic DNA with guanine as its major target. Amino acid-linked cisplatin derivatives are being investigated as alternatives for cisplatin that may exhibit altered binding selectivity such as that found for ornithine-linked cisplatin (Ornplatin, [(Orn)PtCl_2]), which exhibits a preference for adenine over guanine in RNA. Infrared multiple photon dissociation (IRMPD) action spectroscopy experiments and complementary electronic structure calculations are performed on a series of Ornplatin complexes to elucidate the nature of binding of the Orn amino acid to the Pt center and how that binding is influenced by the local environment. The complexes examined in the work include: [(Orn-H)PtCl_2]-, [(Orn)PtCl]+, [(Orn)Pt(H_2O)Cl]+, and [(Orn)PtCl_2+Na]+. In contrast to that found previously for the glycine-linked cisplatin complex (Glyplatin), which binds via the backbone amino and carboxylate groups, binding of Orn in these complexes is found to involve both the backbone and sidechain amino groups. Extensive broadening of the IRMPD spectrum for the [(Orn)Pt(H_2O)Cl]+ complex suggests that either multiple structures are contributing to the measured spectrum or strong intra-molecular hydrogen-binding interactions are present. The results for Ornplatin lead to an interesting discussion about the differences in selectivity and reactivity versus cisplatin.

  11. A First Step toward Personalized Medicine in Osteosarcoma: Pharmacogenetics as Predictive Marker of Outcome after Chemotherapy-Based Treatment.

    PubMed

    Hagleitner, Melanie M; Coenen, Marieke J H; Gelderblom, Hans; Makkinje, Remco R; Vos, Hanneke I; de Bont, Eveline S J M; van der Graaf, Winette T A; Schreuder, H W Bart; Flucke, Uta; van Leeuwen, Frank N; Hoogerbrugge, Peter M; Guchelaar, Henk-Jan; te Loo, Dunja M W M

    2015-08-01

    Overall survival in patients with osteosarcoma is only 60%. Poor response to chemotherapy is the dominant risk factor for poor survival. Pharmacogenetic research can offer possibilities to optimize treatment and improve outcome. We applied a pathway-based approach to evaluate the cumulative effect of genes involved in the metabolism of cisplatin and doxorubicin in relationship to clinical outcome. We included 126 patients with osteosarcoma. To comprehensively assess common genetic variation in the 54 genes selected, linkage disequilibrium (LD; r(2) = 0.8)-based tag-single nucleotide polymorphisms (SNP) strategy was used. A final set of 384 SNPs was typed using Illumina Beadarray platform. SNPs significantly associated with 5-year progression-free survival (PFS) were replicated in another 64 patients with osteosarcoma. We identified five variants in FasL, MSH2, ABCC5, CASP3, and CYP3A4 that were associated with 5-year PFS. Risk stratification based on the combined effects of the risk alleles showed a significant improvement of 5-year PFS. Patients that carried no or only one risk allele had a 5-year PFS of 100% compared with a 5-year PFS of 84.4% for carriers of two or three risk alleles, 66.7% PFS if a patient carried four to five alleles, and a 5-year PFS of 41.8% for patients with >5 risk alleles (P < 0.001). We identified several genes that showed association with PFS in patients with osteosarcoma. These pharmacogenetic risk factors might be useful to predict treatment outcome and to stratify patients immediately after diagnosis and offer the possibility to improve treatment and outcome. ©2015 American Association for Cancer Research.

  12. Usability and Acceptability of a Web-Based Program for Chemotherapy-Induced Peripheral Neuropathy.

    PubMed

    Tofthagen, Cindy; Kip, Kevin E; Passmore, Denise; Loy, Ian; Berry, Donna L

    2016-07-01

    Chemotherapy-induced neuropathy is a painful and debilitating adverse effect of certain chemotherapy drugs. There have not been any patient-centered, easily accessible Web-based interventions to assist with self-management of chemotherapy-induced neuropathy. The aims of this study were to evaluate usability and acceptability and to estimate an effect size of a Web-based intervention for assessing and managing chemotherapy-induced neuropathy. Participants (N = 14) were instructed to complete the Creativity, Optimism, Planning, and Expert Information for Chemotherapy-Induced Peripheral Neuropathy program and provide verbal responses to the program. Participants completed the Chemotherapy Induced Peripheral Neuropathy Assessment Tool and Post-Study System Usability Questionnaire. Iterative changes were made to the COPE-CIPN. Participants were asked to provide feedback on the revised COPE-CIPN, repeat the Chemotherapy Induced Peripheral Neuropathy Assessment Tool, and evaluate acceptability using the Acceptability e-Scale. The COPE-CIPN demonstrated high usability (mean, 1.98 [SD, 1.12]) and acceptability (mean, 4.40 [SD, 0.52]). Comments indicated that the interface was easy to use, and the information was helpful. While neuropathy symptoms continued to increase in this group of patients receiving neurotoxic chemotherapy, there was a decrease in mean level of interference with activities from 53.71 to 39.29 over 3 to 4 months, which indicated a moderate effect (d = 0.39) size. The COPE-CIPN may be a useful intervention to support self-management of chemotherapy-induced neuropathy.

  13. Evaluation of nanoparticle delivered cisplatin in beagles

    NASA Astrophysics Data System (ADS)

    Feldhaeusser, Brittany; Platt, Simon R.; Marrache, Sean; Kolishetti, Nagesh; Pathak, Rakesh K.; Montgomery, David J.; Reno, Lisa R.; Howerth, Elizabeth; Dhar, Shanta

    2015-08-01

    Intracranial neoplasia is a significant cause of morbidity and mortality in both human and veterinary patients, and is difficult to treat with traditional therapeutic methods. Cisplatin is a platinum (Pt)-containing chemotherapeutic agent approved by the Food and Drug Administration; however, substantial limitations exist for its application in canine brain tumor treatment due to the difficulty in crossing the blood-brain barrier (BBB), development of resistance, and toxicity. A modified Pt(iv)-prodrug of cisplatin, Platin-M, was recently shown to be deliverable to the brain via a biocompatible mitochondria-targeted lipophilic polymeric nanoparticle (NP) that carries the drug across the BBB and to the mitochondria. NP mediated controlled release of Platin-M and subsequent reduction of this prodrug to cisplatin allowed cross-links to be formed with the mitochondrial DNA, which have no nucleotide excision repair system, forcing the overactive cancer cells to undergo apoptosis. Here, we report in vitro effects of targeted Platin-M NPs (T-Platin-M-NPs) in canine glioma and glioblastoma cell lines with results indicating that this targeted NP formulation is more effective than cisplatin. In both the cell lines, T-Platin-M-NP was significantly more efficacious compared to carboplatin, another Pt-based chemotherapy, which is used in the settings of recurrent high-grade glioblastoma. Mitochondrial stress analysis indicated that T-Platin-M-NP is more effective in disrupting the mitochondrial bioenergetics in both the cell types. A 14-day distribution study in healthy adult beagles using a single intravenous injection at 0.5 mg kg-1 (with respect to Platin-M) of T-Platin-M-NPs showed high levels of Pt accumulation in the brain, with negligible amounts in the other analyzed organs. Safety studies in the beagles monitoring physical, hematological, and serum chemistry evaluations were within the normal limits on days 1, 7, and 14 after injection of either 0.5 mg kg-1 or 2 mg kg

  14. Plasma chromogranin A marks emesis and serotonin release associated with dacarbazine and nitrogen mustard but not with cyclophosphamide-based chemotherapies.

    PubMed Central

    Cubeddu, L. X.; O'Connor, D. T.; Hoffmann, I.; Parmer, R. J.

    1995-01-01

    Chromogranin A (CgA) is present in high concentrations in enterochromaffin cells, where it is co-localised with serotonin in the storage granules. Plasma CgA has been reported to mark emesis and serotonin release associated with cisplatin treatment. However, it is not known whether plasma CgA could be an indicator of emesis and of serotonin release in patients receiving non-cisplatin chemotherapies. Therefore, in this study we evaluated, in cancer patients, the temporal relationships between the increases in plasma CgA and urinary 5-hydroxyindoleacetic acid (5-HIAA) and the development of vomiting following dacarbazine, nitrogen mustard and cyclophosphamide treatments. Metoclopramide was used as antiemetic. With dacarbazine, nitrogen mustard and cyclophosphamide the median time to the onset of emesis was 2.3, 2.8 and 5.3 h and the duration of intense emesis was 3, 2 and 6 h respectively. Plasma CgA and urinary 5-HIAA increased after dacarbazine- and nitrogen mustard-based chemotherapies, with maximal increases between 4 and 6 h after initiation of drug infusion. The time course for the increases in plasma CgA paralleled that of urinary 5-HIAA and the period of intense emesis. A highly significant (P = 0.0009) positive correlation (r = 0.68) was found between the increases in plasma CgA and in urinary 5-HIAA. Cyclophosphamide treatment was not associated with increases in plasma CgA and in urinary 5-HIAA, despite inducing emesis; this indicates that the increases in CgA and 5-HIAA after dacarbazine and nitrogen mustard are not due to the act of vomiting per se. In summary, plasma CgA is a marker of serotonin release (most likely from enterochromaffin cells) after dacarbazine and nitrogen mustard-based chemotherapies, exocytosis being the most likely mechanism for the release of serotonin. Serotonin released from enterochromaffin cells seems to trigger the emetic response to dacarbazine and nitrogen mustard; however, cyclophosphamide may release serotonin from a

  15. Preventive Effect of Dihydromyricetin against Cisplatin-Induced Nephrotoxicity In Vitro and In Vivo

    PubMed Central

    2016-01-01

    Nephrotoxicity is a frequent severe side effect of cisplatin chemotherapy, limiting its clinical use despite being one of the most potent chemotherapy drugs. Dihydromyricetin is a highly abundant compound purified from the leaves of Ampelopsis grossedentata. Previous studies have demonstrated the anti-inflammatory and antioxidative effects of Dihydromyricetin both in vitro and in vivo, but little is known about the effects of Dihydromyricetin on cisplatin-induced nephrotoxicity and its underlying mechanisms. In the present study, we investigated its potential renoprotective effect and found that Dihydromyricetin ameliorated the renal functional impairment and structural damage caused by cisplatin. Moreover, Dihydromyricetin markedly attenuated cisplatin-induced oxidative stress, as well as protecting against cisplatin-induced inflammation and apoptotic cell death in mouse kidney tissues. These results collectively highlight the potential of DMY as a rational renoprotective agent against cisplatin. PMID:27642358

  16. Electrohydrodynamic encapsulation of cisplatin in poly (lactic-co-glycolic acid) nanoparticles for controlled drug delivery.

    PubMed

    Parhizkar, Maryam; Reardon, Philip J T; Knowles, Jonathan C; Browning, Richard J; Stride, Eleanor; Barbara, Pedley R; Harker, Anthony H; Edirisinghe, Mohan

    2016-10-01

    Targeted delivery of potent, toxic chemotherapy drugs, such as cisplatin, is a significant area of research in cancer treatment. In this study, cisplatin was successfully encapsulated with high efficiency (>70%) in poly (lactic-co-glycolic acid) polymeric nanoparticles by using electrohydrodynamic atomization (EHDA) where applied voltage and solution flow rate as well as the concentration of cisplatin and polymer were varied to control the size of the particles. Thus, nanoparticles were produced with three different drug:polymer ratios (2.5, 5 and 10wt% cisplatin). It was shown that smaller nanoparticles were produced with 10wt% cisplatin. Furthermore, these demonstrated the best sustained release (smallest burst release). By fitting the experimental data with various kinetic models it was concluded that the release is dependent upon the particle morphology and the drug concentration. Thus, these particles have significant potential for cisplatin delivery with controlled dosage and release period that are crucial chemotherapy parameters.

  17. A phase II single institution single arm prospective study with paclitaxel, ifosfamide and cisplatin (TIP) as first-line chemotherapy in high-risk germ cell tumor patients with more than ten years follow-up and retrospective correlation with ERCC1, Topoisomerase 1, 2A, p53 and HER-2 expression.

    PubMed

    Ligia Cebotaru, Cristina; Zenovia Antone, Nicoleta; Diana Olteanu, Elena; Bejinariu, Nona; Buiga, Rares; Todor, Nicolae; Ioana Iancu, Dana; Eliade Ciuleanu, Tudor; Nagy, Viorica

    2016-01-01

    One half of high-risk germ cell tumor (HRGCT) patients relapse after standard chemotherapy. This phase II study evaluated prospectively the toxicity and efficacy in first-line of the paclitaxel-ifosfamide-cisplatin combination (TIP) in HRGCT patients and tried to identify biomarkers that may allow patient-tailored treatments. Between October 1997- September 2000, 28 chemo-naive HRGCT patients were enrolled. Patients received 4 cycles of TIP (paclitaxel 175 mg/m(2) day 1/; ifosfamide 1.2 g/m(2)/day, days 1-5; Mesna 1.2 g/m(2)/day, days 1-5; and cisplatin 20 mg/m(2)/day, days 1-5 every 3 weeks). A non-randomized comparison was made between HRGCT patients treated in the same period with first-line TIP and bleomycin-etoposide-cisplatin (BEP) (28 patients vs 20). In 17 HRGCT patients treated between 1998-2006, ERCC1, Topoisomerase 1 and 2A, p53 and HER-2 expression was retrospectively analysed by immunohistochemistry (IHC) (7 patients with TIP, 10 with BEP), and correlations were made with response to chemotherapy and survival. With a median follow-up of 72 months [range 48+...89+], 5-year disease free survival (DFS) was 55%, with 95% CI 36-72, and the overall survival (OS) was 63%, with 95% CI 44-78. In June 2015, with a median follow-up of 196.47 months (range 177.30-209.27) (>15 years), 12 [%?] patients were alive and disease-free, and 16 [%?] had died (12 specific causes). There was no significant correlation between the expression of ERCC1, Topoisomerase 1 and 2A, HER-2 and p53 and response to treatment. Long-term follow-up showed no difference in OS between TIP vs BEP as first-line therapy. Both regimens had mild toxicity.

  18. Quantitative imaging of platinum based on laser ablation-inductively coupled plasma-mass spectrometry to investigate toxic side effects of cisplatin.

    PubMed

    Köppen, C; Reifschneider, O; Castanheira, I; Sperling, M; Karst, U; Ciarimboli, G

    2015-12-01

    This work presents a quantitative bioimaging method for platinum based on laser ablation-inductively coupled plasma-mass spectrometry and its application for a biomedical study concerning toxic side effects of cisplatin. To trace the histopathology back to cisplatin, platinum was localized and quantified in major functional units of testicle, cochlea, kidney, nerve and brain sections from cisplatin treated mice. The direct consideration of the histology enables precise interpretation of the Pt images and the novel quantitative evaluation approach allows significantly more precise investigations than the pure image. For the first time, platinum was detected and quantified in all major injured structures including organ of Corti of cochlea and seminiferous tubule of testicle. In this way, proximal tubule in kidney, Leydig cells in testicle, stria vascularis and organ of Corti in cochlea and nerve fibers in sciatic nerves are confirmed as targets of cisplatin in these organs. However, the accumulation of platinum in almost all investigated structures also raises questions about more complex pathogenesis including direct and indirect interruption of several biological processes.

  19. Targeting Mechanisms of Resistance to Taxane-Based Chemotherapy

    DTIC Science & Technology

    2008-09-01

    12]. Another interesting gene ; monoamine oxidase A ( MAOA ) was upregulated in patients with PSA relapse (Figure 8A). Quantitative real-time PCR (qRT...from prostate. After excluding genes previously shown to be influenced by the radical prostatectomy procedure, we identified 51 genes with significant...analyses confirmed overexpression of GDF15 may confer resistance to chemotherapy in prostate cancer cells. Gene expression changes after

  20. Targeting Mechanisms of Resistance to Taxane-Based Chemotherapy

    DTIC Science & Technology

    2007-09-01

    gene ; monoamine oxidase A ( MAOA ) was upregulated in patients with PSA relapse (Figure 5A). Quantitative real-time PCR (qRT-PCR) was performed to...resistance and uncover mechanisms or pathways suitable for targeting with the objective of improving tumor responses to chemotherapy. Gene expression...CXCL10 but not IL8 conferring chemoresistance to prostate cancer cells. When using longer term clinical outcome, we found genes correlated with PSA

  1. ERCC1 and the efficacy of cisplatin in patients with resected non-small cell lung cancer.

    PubMed

    Li, Chunhong; Liu, Meiyan; Yan, An; Liu, Wei; Hou, Junjun; Cai, Li; Dong, Xiaoqun

    2014-12-01

    Excision repair cross-complementing gene 1 (ERCC1) protein is proposed as a predictor for cisplatin efficacy in patients with non-small cell lung cancer (NSCLC). However, recent studies declare that ERCC1 is not associated with the response of platinum-based chemotherapy or clinical outcomes. The purpose of this study is to assess whether ERCC1 expression level is linked to cisplatin sensitivity and clinical outcomes in resected NSCLC patients. Paraffin-embedded cancer samples from 112 patients were used for immunohistochemical staining. Cancer cells isolated from fresh tumor tissues were used to determine the sensitivity to cisplatin by MTT assay. The association between ERCC1 expression and cisplatin sensitivity was tested by Spearman's rho test. The correlation of ERCC1 expression with clinicopathologic parameters was evaluated by the chi-square tests. The relationship between variables and survival was assessed by log-rank test. Overall survival (OS) and disease-free survival (DFS) curves were plotted by the Kaplan-Meier method. Cox proportional hazards model was used for multivariate analysis of survival. ERCC1 expression was significantly correlated with the sensitivity of cisplatin in vitro (p < 0.01, r = 0.37). ERCC1 was not associated with OS (p = 0.17) or DFS (p = 0.13) in patients with resected NSCLC. ERCC1 is not a sensible marker for the choice of treatment in clinical patients with resected NSCLC.

  2. Tumour chemotherapy strategy based on impulse control theory.

    PubMed

    Ren, Hai-Peng; Yang, Yan; Baptista, Murilo S; Grebogi, Celso

    2017-03-06

    Chemotherapy is a widely accepted method for tumour treatment. A medical doctor usually treats patients periodically with an amount of drug according to empirical medicine guides. From the point of view of cybernetics, this procedure is an impulse control system, where the amount and frequency of drug used can be determined analytically using the impulse control theory. In this paper, the stability of a chemotherapy treatment of a tumour is analysed applying the impulse control theory. The globally stable condition for prescription of a periodic oscillatory chemotherapeutic agent is derived. The permanence of the solution of the treatment process is verified using the Lyapunov function and the comparison theorem. Finally, we provide the values for the strength and the time interval that the chemotherapeutic agent needs to be applied such that the proposed impulse chemotherapy can eliminate the tumour cells and preserve the immune cells. The results given in the paper provide an analytical formula to guide medical doctors to choose the theoretical minimum amount of drug to treat the cancer and prevent harming the patients because of over-treating.This article is part of the themed issue 'Horizons of cybernetical physics'.

  3. Activation of surrogate death receptor signaling triggers peroxynitrite-dependent execution of cisplatin-resistant cancer cells

    PubMed Central

    Seah, S; Low, I C C; Hirpara, J L; Sachaphibulkij, K; Kroemer, G; Brenner, C; Pervaiz, S

    2015-01-01

    Platinum-based drugs remain as the cornerstone of cancer chemotherapy; however, development of multidrug resistance presents a therapeutic challenge. This study aims at understanding the molecular mechanisms underlying resistance to cisplatin and unraveling surrogate signaling networks that could revert sensitivity to apoptosis stimuli. We made use of three different sets of cell lines, A549 and H2030 non-small-cell lung cancer (NSCLC) and A2780 ovarian cancer cells and their cisplatin-resistant variants. Here we report that cisplatin-resistant cell lines displayed a multidrug-resistant phenotype. Changes in mitochondrial metabolism and defective mitochondrial signaling were unraveled in the resistant cells. More interestingly, a marked increase in sensitivity of the resistant cells to death receptor-induced apoptosis, in particular TRAIL (TNF-related apoptosis-inducing ligand)-mediated execution, was observed. Although this was not associated with an increase in gene transcription, a significant increase in the localization of TRAIL death receptor, DR4, to the lipid raft subdomains of plasma membrane was detected in the resistant variants. Furthermore, exposure of cisplatin-resistant cells to TRAIL resulted in upregulation of inducible nitric oxide synthase (iNOS) and increase in nitric oxide (NO) production that triggered the generation of peroxynitrite (ONOO−). Scavenging ONOO− rescued cells from TRAIL-induced apoptosis, thereby suggesting a critical role of ONOO− in TRAIL-induced execution of cisplatin-resistant cells. Notably, preincubation of cells with TRAIL restored sensitivity of resistant cells to cisplatin. These data provide compelling evidence for employing strategies to trigger death receptor signaling as a second-line treatment for cisplatin-resistant cancers. PMID:26492363

  4. MT 2A Phosphorylation by PKC Mu/PKD Influences Chemosensitivity to Cisplatin in Prostate Cancer

    DTIC Science & Technology

    2008-11-01

    reduce MT induction in mice inocu- ated with human or murine bladder tumor cells, hich markedly enhanced the antitumor activity f cisplatin and other...85–98, 1999. B ROLOGY 67 (6), 200611. Kondo Y, Yamagata K, Satoh M, et al: Optimal admin- stration schedule of cisplatin for bladder tumor with...analysis. Chemotherapy and radiation sensitivity assays of cells after treatment with cisplatin or radiation were performed in the presence, or absence, of

  5. Pros and cons of intraperitoneal chemotherapy in the treatment of epithelial ovarian cancer.

    PubMed

    Zeimet, Alain G; Reimer, Daniel; Radl, Alice C; Reinthaller, Alexander; Schauer, Christian; Petru, Edgar; Concin, Nicole; Braun, Stephan; Marth, Christian

    2009-07-01

    Development of the pros and cons of intraperitoneal (IP) chemotherapy in the treatment of epithelial ovarian cancer based on the most prominent data published on the evolution of IP chemotherapy and on experience with this therapeutic strategy in clinical routine. The literature published on IP chemotherapy in ovarian cancer between 1970 and 2008 was identified systematically by computer-based searches in MEDLINE and the Cochrane Library. Furthermore, a preliminary analysis of data recorded during an observational nationwide multicenter study of the Austrian AGO on IP-IV chemotherapy using the GOG-172 treatment regimen was performed. The literature review unequivocally revealed a significantly greater toxicity for IP than for intravenous (IV) cisplatin-based chemotherapy. However, according to a Cochrane meta-analysis, IP-IV administration of chemotherapy is associated with a 21.6% decrease in the risk for death. In agreement with earlier reports, the most frequently mentioned side-effects in the Austria-wide observational study were long-lasting neurotoxicity, abdominal pain, fatigue, gastrointestinal and metabolic toxicities, and catheter-related complications. Most of these toxicities were identified as mirroring the toxicity profile of high-dose IV cisplatin (>or=100 mg/m(2)). In some patients, the classic IP-IV regimen with cisplatin/paclitaxel was changed to an alternative schedule comprising carboplatin AUC 5 (d1) and weekly paclitaxel 60 mg/m(2) (d1, 8, 15) completely administered via the IP route. This treatment was better tolerated and quality of life was significantly less compromised. However, neutropenia and thrombocytopenia were the limiting side-effects of this IP regimen. In cases where optimal cytoreduction with residual disease chemotherapy should be given serious consideration, even at the expense of significantly increased, but manageable toxicity.

  6. Retrospective study of efficacy and toxicity on patients older than 70 years within a randomized clinical trial of two cisplatin-based combinations in patients with small-cell lung cancer.

    PubMed

    Safont, María José; Artal-Cortes, Angel; Sirera, Rafael; Gómez-Codina, José; González-Larriba, José Luis; Barneto, Isidoro; Carrato, Alfredo; Isla, Dolores; Rosell, Rafael; Camps, Carlos

    2009-01-01

    A retrospective analysis based on the Spanish Lung Cancer Group (SLCG) clinical trial of high-dose epirubicin/cisplatin in patients with small-cell lung cancer (SCLC) was performed. Patients younger than 70 years vs. older than 70 years old were analyzed to evaluate the influence of age on response to treatment, toxicity, time to progression (TTP) and overall survival (OS) of the chemotherapy schedule. Three hundred and thirty eight patients <70 years and sixty-four >70 years, were analyzed. Objective responses were similar in both groups. In patients less than 70 years higher TTP (36 weeks vs. 32 weeks) and OS (47 weeks vs. 42 weeks) were seen, attributable to the improved results observed in the subgroup of patients with limited disease (LD). No significant differences were observed when toxicity profile of both groups was compared, except for a higher rate of febrile neutropenia observed in the elderly group with extensive disease (4.6% vs. 8.8%, p=0.01). In the subgroup of patients with LD, elderly patients received less total cisplatin dose (401 vs. 508 mg/m(2), p=0.01) although less treatment delays were reported (10 days vs. 15 days, p=0.05). Age was likely to be a negative prognostic factor for OS of elderly patients with LD. It also seemed to be related to a greater dose reduction, which may explain that toxic episodes and delays occurred more frequently in the younger patients receiving the full scheduled dose. However, the definitive reason to explain this could not be established due to the characteristics of our analysis.

  7. Remarkable response in 2 cases of Advanced Poorly Differentiated Thyroid Carcinoma with liposomal doxorubicin plus cisplatin.

    PubMed

    Yang, Haiyan; Chen, Zhongjian; Wu, Meijuan; Lei, Tao; Yu, Haifeng; Ge, Minghua

    2016-06-02

    Poorly Differentiated Thyroid Carcinoma (PDTC), especially advanced PDTC, is an aggressive disease and displays a much poorer prognosis compared with well differentiated thyroid carcinoma. Surgery is the recommended treatment in the early stage of PDTC, however, no effective treatment modalities are currently available for advanced PDTCMethods: Two advanced PDTC patients with no radioiodine uptake adopted a cytotoxic chemotherapy with liposomal doxorubicin (35 mg/m(2), day 1) plus cisplatin (75 mg/m(2), day1-3) every 3 weeks. Computer tomography (CT) was performed after 6 cycles (case 1) or 5 cycles (case 2) of chemotherapy Our patients achieved remarkable response with one a Complete Remission (CR) and the other a very good Partial Remission (PR)Conclusion: Our findings indicate that liposomal doxorubicin-based chemotherapy regimens might produce response in PDTC patients, and improve their overall survival and quality of life. Hence we believe this result is very important for oncologists in treating PDTC.

  8. Anti-tumor effects of canine adipose tissue-derived mesenchymal stromal cell-based interferon-β gene therapy and cisplatin in a mouse melanoma model.

    PubMed

    Seo, Kyoung-Won; Lee, Hee-Woo; Oh, Ye-In; Ahn, Jin-Ok; Koh, Ye-Rin; Oh, Seung-Hyun; Kang, Sung-Keun; Youn, Hwa-Young

    2011-09-01

    Adipose tissue (AT)-derived mesenchymal stromal cells (MSC) (AT-MSC) represent a novel tool for delivering therapeutic genes to tumor cells. Interferon (IFN)-β is a cytokine with pleiotropic cellular functions, including anti-proliferative, immunomodulatory and anti-angiogenic activities. The purpose of this study was to engineer canine AT-MSC (cAT-MSC) producing IFN-β and to evaluate the anti-tumor effect of cAT-MSC-IFN-β combined with cisplatin in mouse melanoma model. cAT-MSC engineered to express mouse IFN-β were generated using a lentiviral vector (cAT-MSC-IFN-β) and the secreted IFN-β-induced inhibition of tumor cell growth and apoptosis on B16F10 cells was investigated in vitro prior to in vivo studies. Melanoma-bearing mouse was developed by injecting B16F10 cells subcutaneously into 6-week-old C57BL/6 mice. After 14 days, cisplatin (10 mg/kg) was injected intratumorally, and 3 days later the engineered cAT-MSC were injected subcutaneously every 3 days to death. Tumor volume and survival times were measured. The combination treatment of cAT-MSC-IFN-β with cisplatin was more effective in inhibiting the growth of melanoma and resulted in significantly extended survival time than both an unengineered cAT-MSC-cisplatin combination group and a cisplatin-alone group. Interestingly, subcutaneously injected cAT-MSC-IFN-β were migrated to tumor sites. Our data suggest that canine AT-MSC could serve as a powerful cell-based delivery vehicle for releasing therapeutic proteins to tumor lesions. Maximal anti-tumor effects were seen when this therapy was combined with a DNA-damaging chemotherapeutic agent. This study demonstrates the possible applicability of AT-MSC-mediated IFN-β in treating canine and human cancer patients.

  9. Treatment of intraabdominal desmoplastic small round cell tumor with ifosfamide-based chemotherapy.

    PubMed

    Ujihara, Masaki; Ando, Takafumi; Watanabe, Osamu; Asada, Takahiro; Yamashita, Katsuya; Ichihara, Toru; Nakamura, Etsuko; Goto, Hidemi

    2010-02-01

    Intraabdominal desmoplastic small round cell tumor (IDSRCT) is a rare tumor with poor prognosis that usually develops in the peritoneal cavity, often in childhood and adolescence. This tumor typically arises as single or multiple masses, and is characterized by diffuse peritoneal implants and the involvement of regional lymph nodes. Because most patients are unable to achieve a complete response with chemotherapy alone, extensive efforts have been made to develop more effective chemotherapy regimens. Here, we report on a case of IDSRCT in a 33-year-old man treated with ifosfamide (IFM)-based chemotherapy. Before treatment initiation, the patient had extensive ascites in the peritoneal cavity and was experiencing abdominal fullness and anorexia. Currently, 8 months after his initial presentation, he is still undergoing chemotherapy and is in good general condition.

  10. Tobacco Mosaic Virus-Delivered Cisplatin Restores Efficacy in Platinum-Resistant Ovarian Cancer Cells.

    PubMed

    Franke, Christina E; Czapar, Anna E; Patel, Ravi B; Steinmetz, Nicole F

    2017-09-19

    Platinum resistance in ovarian cancer is the major determinant of disease prognosis. Resistance can first appear at the onset of disease or develop in response to platinum-based chemotherapy. Due to poor response to alternate chemotherapies and lack of targeted therapies, there is an urgent clinical need for a new avenue toward treatment of platinum-resistant (PR) ovarian cancer. Nanoscale delivery systems hold potential to overcome resistance mechanisms. In this work, we present tobacco mosaic virus (TMV) as a nanocarrier for cisplatin for treatment of PR ovarian cancer cells. The TMV-cisplatin conjugate (TMV-cisPt) was synthesized using a charge-driven reaction that, like a classic click reaction, is simple and reliable for large-scale production. Up to ∼1900 cisPt were loaded per TMV-cisPt with biphasic release profiles characterized by a fast half-life (t1) of ∼1 h and slow half-life (t2) of ∼12 h independent of pH. Efficient cell uptake of TMV was observed when incubated with ovarian cancer cells, and TMV-cisPt demonstrated superior cytotoxicity and DNA double strand breakage (DSB) in platinum-sensitive (PS) and PR cancer cells when compared to free cisplatin. The cytotoxicity in PR ovarian cancer cells and overall lower effective dosage requirement makes TMV-cisPt a powerful candidate for improved ovarian cancer treatment strategies.

  11. Cetuximab intensifies cisplatin-induced testicular toxicity.

    PubMed

    Levi, Mattan; Popovtzer, Aron; Tzabari, Moran; Mizrachi, Aviram; Savion, Naphtali; Stemmer, Salomon M; Shalgi, Ruth; Ben-Aharon, Irit

    2016-07-01

    Epidermal growth factor receptor (EGFR) has proliferative properties in the testis. Cetuximab, an anti-EGFR, is administered together with chemotherapy to patients with various types of cancer. This studies aim was to investigate the effect of cetuximab on testicular function. Adult male mice were injected with cetuximab (10 mg/kg), cisplatin (8 mg/kg) or a combination of both, and killed one week or one month later. The doses were chosen by human equivalent dose calculation. Testicular function was evaluated by epididymal-spermatozoa total motile count and sperm motility, weights of testes and epididymides, and the level of anti-Müllerian hormone (AMH) in the serum. Immunohistochemistry was performed to examine germ cell proliferation (Ki-67), apoptosis (Terminal transferase-mediated deoxyuridine 5-triphosphate nick-end labelling), reserve (DAZL-Deleted in azoospermia-like, Promyelocytic leukaemia zinc-finger), blood vessels (CD34) and Sertoli cells (GATA-4). Administration of cetuximab alone increased testicular apoptosis and decreased epididymal-spermatozoa total motile count over time. When added to cisplatin, cetuximab exacerbated most of the recorded testicular parameters, compared with the effect of cisplatin alone, including testis and epididymis weights, epididymal-spermatozoa total motile count, AMH concentration, meiosis and apoptosis. In conclusion, cetuximab has only a mild effect on testicular reserve, but when added to cisplatin, it exacerbates cisplatin-induced testicular toxicity.

  12. Prognostic markers of survival after combined mitotane- and platinum-based chemotherapy in metastatic adrenocortical carcinoma.

    PubMed

    Malandrino, Pasqualino; Al Ghuzlan, Abir; Castaing, Marine; Young, Jacques; Caillou, Bernard; Travagli, Jean-Paul; Elias, Dominique; de Baere, Thierry; Dromain, Clarisse; Paci, Angelo; Chanson, Philippe; Schlumberger, Martin; Leboulleux, Sophie; Baudin, Eric

    2010-09-01

    To progress in the stratification of the first-line therapeutic management of metastatic adrenocortical carcinoma (ACC), we searched for prognostic parameters of survival in patients treated with combined mitotane- and cisplatinum-based chemotherapy as first-line. We retrospectively studied prospectively collected parameters from 131 consecutive patients with metastatic ACC (44 with a tissue specimen available) treated at the Gustave Roussy Institute with mitotane- and platinum-based chemotherapy. Fifty-five patients with clinical, pathological, and morphological data available together with treatment characteristics including detailed follow-up were enrolled. Plasma mitotane levels and ERCC1 protein staining were analyzed. Response was analyzed according to RECIST criteria as well as overall survival (OS) from the start of cisplatinum-based chemotherapy. Parameters impacting on OS were evaluated by univariate analysis, and then analyzed by multivariate analysis. Using a landmark method, OS according to response to chemotherapy was analyzed. Objective response to combined mitotane- and cisplatinum-based chemotherapy was 27.3%. Median OS was 1 year. In the univariate analysis, resection of the primary, time since diagnosis, mitotane monotherapy as single first-line treatment, number of affected organs, plasma mitotane above 14 mg/l, and objective response were predictors of survival. In the multivariate analysis, mitotane level > or =14 mg/l and objective response to platinum-based chemotherapy were found to be independent predictors of survival (P=0.03 and <0.001). Our study suggests a prognostic role for mitotane therapy and objective response to platinum-based chemotherapy.

  13. Possible prediction of the response of esophageal squamous cell carcinoma to neoadjuvant chemotherapy based on gene expression profiling.

    PubMed

    Shen, Lu-Yan; Wang, Hui; Dong, Bin; Yan, Wan-Pu; Lin, Yao; Shi, Qi; Chen, Ke-Neng

    2016-01-26

    Heterogeneous efficacy of neoadjuvant chemotherapy has led to controversies that have limited its application in clinical practice. Thus, we aimed to identify potential biomarkers predicting esophageal squamous cell carcinoma (ESCC) chemo-responsiveness by gene expression profiling. CCK8 assay was used to evaluate the growth inhibitory effect of different concentrations of cisplatin and paclitaxel on the ESCC cell lines EC109, KYSE450, KYSE410, KYSE510, and KYSE150 to differentiate between chemosensitive and chemoresistant cell lines. Gene expression profiling and Real-time PCR were applied to analyze and validate the gene expression differences between chemosensitive and chemoresistant cell lines. IHC was conducted to examine the expression of selected target markers MUC4, MUC13, and MUC20 in 186 ESCC resection samples and the relationships between their expression and tumor regression grade was analyzed. Moreover, RNAi was conducted to instantly block the expression of MUC4, MUC13, and MUC20 to observe their influences on chemo-responsiveness. EC109 was found to be relatively sensitive to both cisplatin and paclitaxel, while KYSE410 was relatively resistant to cisplatin, KYSE510 was relatively resistant to paclitaxel. Gene expression profiling analysis showed that 2018 genes were differentially expressed in sensitive cell line compared to resistant cell lines. The expression patterns of MUC4, MUC13, MUC20 were validated. Low expression of MUC4 and MUC20 in resection samples was significantly correlated with better TRG. Blockage of MUC20 and MUC13 decreased the drug-resistance capacity and chemosensitivity, respectively. MUC4 and MUC20 were identified as potential biomarkers for predicting the efficacy of neoadjuvant chemotherapy in ESCC patients.

  14. 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.

  15. S-1-Based Chemotherapy versus Capecitabine-Based Chemotherapy as First-Line Treatment for Advanced Gastric Carcinoma: A Meta-Analysis

    PubMed Central

    Wang, Zhi-qiang; Zhang, Dong-sheng; Luo, Hui-yan; Qiu, Miao-zhen; Wang, Feng-hua; Ren, Chao; Zeng, Zhao-lei; Xu, Rui-hua

    2013-01-01

    Background Although both oral fluoropyrimidines were reported effective and safe, doubts exist about whether S-1 or capecitabine is more advantageous in advanced gastric carcinoma (AGC). Herein, we performed a meta-analysis to comprehensively compare the efficacy and safety of S-1-based chemotherapy versus capecitabine-based chemotherapy as first-line treatment for AGC. Methods PubMed/Medline, EmBase, Cochrane library, and China National Knowledge Infrastructure databases were searched for articles comparing S-1-based chemotherapy to capecitabine-based chemotherapy for AGC. Primary outcomes were overall response rate (ORR), time to progression (TTP), overall survival (OS), progression-free probability, and survival probability. Secondary outcomes were toxicities. Fixed-effects model were used and all the results were confirmed by random-effects model. Results Five randomized controlled trials and five cohort studies with 821 patients were included. We found equivalent ORR (38.3% vs. 39.1%, odds ratio [OR] 0.92, 95% confidence interval [CI] 0.69-1.24, P = 0.59), TTP (harzad ratio [HR] 0.98, 95% CI 0.82-1.16, P = 0.79), OS (HR 0.99, 95% CI 0.87-1.13, P = 0.91), progression-free probability (3-month OR 1.02, 95% CI 0.62-1.68, P = 0.94; 6-month OR 1.34, 95% CI 0.88-2.04, P = 0.18) and survival probability (0.5-year OR 0.90, 95% CI 0.61-1.31, P =0.57; 1-year OR 0.97, 95% CI 0.70- 1.33, P = 0.84; 2-year OR 1.15, 95% CI 0.61-2.17, P = 0.66). Equivalent grade 3 to 4 hematological and non-hematological toxicities were found except hand-foot syndrome was less prominent in S-1-based chemotherapy (0.3% vs. 5.9%, OR 0.19, 95% CI 0.06-0.56, P = 0.003). There’re no significant heterogeneity and publication bias. Cumulative analysis found stable time-dependent trend. Consistent results stratified by study design, age, regimen, cycle, country were observed. Conclusion S-1-based chemotherapy was associated with non-inferior antitumor efficacy and better safety profile, compared

  16. Adjuvant chemotherapy for early-stage cervical cancer.

    PubMed

    Asano, Hiroshi; Todo, Yukiharu; Watari, Hidemichi

    2016-04-01

    The aim of this review is to address the current status of adjuvant chemotherapy alone in early-stage cervical cancer treatments in the literature. At present, the therapeutic effect of adjuvant chemotherapy alone after radical surgery (RS) has not yet been established, and radiation therapy (RT) or concurrent chemoradiotherapy (CCRT) is recommended as the standard adjuvant therapy after RS for early-stage cervical cancer in various guidelines. The main purpose of adjuvant therapy after RS, however, should be to reduce extrapelvic recurrence rather than local recurrence, although adjuvant RT or CCRT has survival benefits for patients with intermediate- or high-risk factors for recurrence. Moreover, several studies reported that adjuvant therapies including RT were associated with a higher incidence of complications, such as lymphedema, bowel obstruction and urinary disturbance, and a lower grade of long-term quality of life (QOL) or sexual functioning than adjuvant chemotherapy alone. The effect of adjuvant chemotherapy alone for early-stage cervical cancer with intermediate- or high-risk factors for recurrence were not fully investigated in prospective studies, but several retrospective studies suggest that the adjuvant effects of chemotherapy alone are at least similar to that of RT or CCRT in terms of recurrence rate, disease-free survival, or overall survival (OS) with lower incidence of complications. Whereas cisplatin based combination regimens were used in these studies, paclitaxel/cisplatin (TP) regimen, which is currently recognized as a standard chemotherapy regimen for patients with metastatic, recurrent or persistent cervical cancer by Gynecologic Oncology Group (GOG), had also survival benefit as an adjuvant therapy. Therefore, it may be worth considering a prospective randomized controlled trial (RCT) of adjuvant chemotherapy alone using TP regimen versus adjuvant RT as an alternative adjuvant therapy. Because early-stage cervical cancer is a curable

  17. Adjuvant chemotherapy for early-stage cervical cancer

    PubMed Central

    Asano, Hiroshi; Todo, Yukiharu; Watari, Hidemichi

    2016-01-01

    The aim of this review is to address the current status of adjuvant chemotherapy alone in early-stage cervical cancer treatments in the literature. At present, the therapeutic effect of adjuvant chemotherapy alone after radical surgery (RS) has not yet been established, and radiation therapy (RT) or concurrent chemoradiotherapy (CCRT) is recommended as the standard adjuvant therapy after RS for early-stage cervical cancer in various guidelines. The main purpose of adjuvant therapy after RS, however, should be to reduce extrapelvic recurrence rather than local recurrence, although adjuvant RT or CCRT has survival benefits for patients with intermediate- or high-risk factors for recurrence. Moreover, several studies reported that adjuvant therapies including RT were associated with a higher incidence of complications, such as lymphedema, bowel obstruction and urinary disturbance, and a lower grade of long-term quality of life (QOL) or sexual functioning than adjuvant chemotherapy alone. The effect of adjuvant chemotherapy alone for early-stage cervical cancer with intermediate- or high-risk factors for recurrence were not fully investigated in prospective studies, but several retrospective studies suggest that the adjuvant effects of chemotherapy alone are at least similar to that of RT or CCRT in terms of recurrence rate, disease-free survival, or overall survival (OS) with lower incidence of complications. Whereas cisplatin based combination regimens were used in these studies, paclitaxel/cisplatin (TP) regimen, which is currently recognized as a standard chemotherapy regimen for patients with metastatic, recurrent or persistent cervical cancer by Gynecologic Oncology Group (GOG), had also survival benefit as an adjuvant therapy. Therefore, it may be worth considering a prospective randomized controlled trial (RCT) of adjuvant chemotherapy alone using TP regimen versus adjuvant RT as an alternative adjuvant therapy. Because early-stage cervical cancer is a curable

  18. Phase II multi-institutional prospective randomised trial comparing S-1+paclitaxel with S-1+cisplatin in patients with unresectable and/or recurrent advanced gastric cancer

    PubMed Central

    Mochiki, E; Ogata, K; Ohno, T; Toyomasu, Y; Haga, N; Fukai, Y; Aihara, R; Ando, H; Uchida, N; Asao, T; Kuwano, H

    2012-01-01

    Background: A combination of S-1 and cisplatin has been shown to be effective with acceptable safety for the first-line treatment of far-advanced gastric cancer in Japan. This is the first randomised phase II trial to compare S-1+paclitaxel with S-1+cisplatin in this setting. Methods: Patients with unresectable and/or recurrent advanced gastric cancer were randomly assigned to receive one of the two regimens: S-1 (40 mg m−2 twice daily) on days 1–14 plus paclitaxel (60 mg m−2) on days 1, 8, and 15 of a 4-week cycle (S-1+paclitaxel) or S-1 (40 mg m−2 twice daily) on days 1–21 plus cisplatin (60 mg m−2) on day 8 of a 5-week cycle (S-1+cisplatin). The primary end point was the response rate (RR). Secondary end points included progression-free survival (PFS), overall survival (OS), and safety. Results: A total of 83 patients were eligible for safety and efficacy analyses. In the S-1+paclitaxel and S-1+cisplatin groups, RRs (52.3% vs 48.7% P=0.74) and median PFS (9 vs 6 months; P=0.50) were similar. The median OS was similar in the S-1+paclitaxel and S-1+cisplatin groups (16 vs 17 months; P=0.84). The incidence of grade 3 or higher haematological toxicity was 19.0% with S-1+paclitaxel and 19.5% with S-1+cisplatin. The incidence of grade 3 or higher non-haematological toxicity was 14.2% with S-1+paclitaxel and 17.1% with S-1+cisplatin. Conclusion: S-1+paclitaxel was suggested to be a feasible and effective non-platinum-based regimen for chemotherapy in patients with advanced gastric cancer. Our results should be confirmed in multicenter, phase III-controlled clinical trials. PMID:22617130

  19. Retroperitoneal teratoma with somatic malignant transformation: a papillary renal cell carcinoma in a testicular germ cell tumour metastasis following platinum-based chemotherapy.

    PubMed

    Zeh, Nina; Wild, Peter J; Bode, Peter K; Kristiansen, Glen; Moch, Holger; Sulser, Tullio; Hermanns, Thomas

    2013-02-12

    Malignant transformation describes the phenomenon in which a somatic component of a germ cell teratoma undergoes malignant differentiation. A variety of different types of sarcoma and carcinoma, all non-germ cell, have been described as a result of malignant transformation. A 33-year-old man presented with a left testicular mass and elevated tumour markers. Staging investigations revealed retroperitoneal lymphadenopathy with obstruction of the left ureter and distant metastases. Histopathology from the left radical orchiectomy showed a mixed germ cell tumour (Stage III, poor prognosis). The ureter was stented and four cycles of cisplatin, etoposide and bleomycin chemotherapy administered. After initial remission, the patient recurred four years later with a large retroperitoneal mass involving the renal vessels and the left ureter. Left retroperitoneal lymph node dissection with en-bloc resection of the left kidney was performed.Histopathology revealed a germ cell tumour metastasis consisting mainly of mature teratoma. Additionally, within the teratoma a papillary renal cell carcinoma was found. The diagnosis was supported by immunohistochemistry showing positivity for AMACR, CD10 and focal expression of RCC and CK7. There was no radiological or histo-pathological evidence of a primary renal cell cancer. To the best of our knowledge, malignant transformation into a papillary renal cell carcinoma has not been reported in a testicular germ cell tumour metastasis following platinum-based chemotherapy. This histological diagnosis might have implications for potential future therapies. In the case of disease recurrence, renal cell cancer as origin of the recurrent tumour has to be excluded because renal cell carcinoma metastases would not respond well to the classical germ cell tumour chemotherapy regimens.

  20. Enhancement of Cisplatin Nephrotoxicity by Morphine and Its Attenuation by the Opioid Antagonist Naltrexone.

    PubMed

    Aminian, Atefeh; Javadi, Shiva; Rahimian, Reza; Dehpour, Ahmad Reza; Asadi Amoli, Fahimeh; Moghaddas, Payman; Ejtemaei Mehr, Shahram

    2016-07-01

    Nephrotoxicity is a major side effect of cisplatin, a widely used chemotherapy agent. Morphine and other opioids are also used extensively in different types of cancer for the clinical management of pain associated with local or metastatic neoplastic lesions. In addition to its analgesic effects, morphine has also been reported to possess potential immunomodulatory and antioxidant properties. Herein, we investigated the effects of morphine in a rat model of cisplatin-induced nephrotoxicity. Following administration of a single dose of cisplatin (5 mg/kg), animals received intraperitoneal injections of morphine (5 mg/kg/day) and/or naltrexone (20 mg/kg/day), an opioid antagonist, for 5 days. Cisplatin-induced nephrotoxicity was detected by a significant increase in plasma urea and creatinine levels in addition to alterations in kidney tissue morphology. Levels of TNF-α and IL-1β were significantly increased in the renal tissue in cisplatin group. Moreover, glutathione (GSH) concentration and superoxide dismutase activity were significantly reduced in renal tissue in cisplatin group compared with control animals. Treatment with morphine aggravated the deleterious effects of cisplatin at clinical, biochemical and histopathological levels; whereas naltrexone diminished the detrimental effects of morphine in animals receiving morphine and cisplatin. Morphine or naltrexone alone had no effect on the mentioned parameters. Our findings indicate that concomitant treatment with morphine might intensify cisplatin-induced renal damage in rats. These findings suggest that morphine and other opioids should be administered cautiously in patients receiving cisplatin chemotherapy.

  1. May glutamine addiction drive the delivery of antitumor cisplatin-based Pt(IV) prodrugs?

    PubMed

    Ravera, Mauro; Gabano, Elisabetta; Tinello, Stefano; Zanellato, Ilaria; Osella, Domenico

    2017-02-01

    A small series of Pt(IV) prodrugs containing Gln-like (Gln=glutamine) axial ligands has been designed with the aim to take advantage of the increased demand of Gln showed by some cancer cells (glutamine addiction). In complex 4 the Gln, linked through the α-carboxylic group is recognized by the Gln transporters, in particular by the solute carrier transporter SLC1A5. All compounds showed cellular accumulation, as well as antiproliferative activity, related to their lipophilicity, as already demonstrated for the majority of Pt(IV) prodrugs, that enter cells mainly by passive diffusion. On the contrary, when the Gln concentration in cell medium is near or lower to the physiological value, complex 4 acts as a Trojan horse: it enters SLC1A5-overexpressing cells, where, upon reduction, it releases the active metabolite cisplatin and the Gln-containing ligand, thus preventing any possible extrusion by the L-type amino acid transporter LAT1. This selective mechanism could decrease off-target accumulation of 4 and, consequently, Pt-associated side-effects.

  2. Incorporation of TIP (paclitaxel, ifosfamide, cisplatin) into first-line therapy for intermediate to poor risk testicular germ cell tumors with unfavorable marker decline after initial two cycles chemotherapy: a report of three cases.

    PubMed

    Ishioka, Jun-Ichiro; Kageyama, Yukio; Ichiyanagi, Nobutaka; Fukuda, Hiroshi; Higashi, Yotsuo

    2007-05-01

    Three patients of advanced-non-seminomatous germ cell tumors (International Germ Cell Cancer Collaborative Group classification: poor risk, 2; intermediate, 1) without evidence of a second primary germ cell tumor were treated. The patients received two cycles of standard BEP (bleomycin, etopside, cisplatin) or VIP/VB (etoposide, ifosphamide, cisplatin/vinblastine, bleomycin) therapy first. All patients in this trial showed unfavorable marker response to these therapies and received four cycles of TIP subsequently. A complete remission was observed in all patients. No patient experienced life-threatening toxicity. During the 34-month observation period, all patients were alive without progression.

  3. Castrate-resistant prostate cancer with peritoneal metastases treated with docetaxel-based chemotherapy.

    PubMed

    Rizk, Rita; Danse, Etienne; Aydin, Selda; Tombal, Bertrand; Machiels, Jean-Pascal

    2014-01-01

    To identify the risk factors, characteristics and prognosis of patients treated with docetaxel-based chemotherapy for peritoneal carcinomatosis due to metastatic castrate-resistant prostate cancer (mCRPC). We retrospectively reviewed our series of mCRPC patients with peritoneal metastases treated with docetaxel-based chemotherapy between 2004 and 2010. Six patients were identified from our institutions' internal cancer registry. Three out of these patients had been treated with laparoscopic radical prostatectomy (LRP). In addition to peritoneal metastases, other metastatic sites were mainly visceral. Only 1 patient developed bone metastases. Peritoneal carcinomatosis occurred mainly in patients with a high Gleason (= or >6) score since 5 out of our 6 patients had a Gleason score ≥7. All 6 patients were treated with docetaxel-based chemotherapy when they developed castration resistance. Five patients benefitted from chemotherapy according to their PSA or RECIST responses. Median survival from the start of docetaxel was 24.5 months. Our retrospective analysis suggests that peritoneal carcinomatosis occurs mainly in patients with a high Gleason score. It is also possible that tumor seeding occurs during LRP. Patients with peritoneal carcinomatosis resistant to castration seem to benefit from docetaxel-based chemotherapy. © 2013 S. Karger AG, Basel.

  4. Nanoscale Drug Delivery Platforms Overcome Platinum-Based Resistance in Cancer Cells Due to Abnormal Membrane Protein Trafficking

    PubMed Central

    Xue, Xue; Hall, Matthew D.; Zhang, Qiang; Wang, Paul C.; Gottesman, Michael M.; Liang, Xing-Jie

    2014-01-01

    The development of cellular resistance to platinum-based chemotherapies is often associated with reduced intracellular platinum concentrations. In some models, this reduction is due to abnormal memb