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Sample records for adjuvant chemotherapy fam

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

    PubMed

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

    2010-01-01

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

  2. [Adjuvant chemotherapy of adults soft tissue sarcomas].

    PubMed

    Bui-Nguyen, B; Italiano, A; Delva, F; Toulmond, M

    2010-06-01

    The main progress in the management of soft tissue sarcomas have been obtained in the field of local control. Although the main evolutive, vital, risk of these diseases is metastatic dissemination, efficacy of adjuvant chemotherapy remains a controversial issue. Thus, adjuvant chemotherapy cannot be considered as a standard for any situation. The last results of clinical trials, meta-analysis and population studies are presented and discussed in this article. New therapeutic strategies are to be developed to prevent metastases in soft tissue sarcomas. This needs a better understanding of the biology of those tumors, of metastases risk factors and of the determinants of systemic therapies efficacy in these tumors. PMID:20547481

  3. Adjuvant chemotherapy for endometrial cancer after hysterectomy

    PubMed Central

    Johnson, Nick; Bryant, Andrew; Miles, Tracie; Hogberg, Thomas; Cornes, Paul

    2014-01-01

    Background Endometrial adenocarcinoma (womb cancer) is a malignant growth of the lining (endometrium) of the womb (uterus). It is distinct from sarcomas (tumours of the uterine muscle). Survival depends the risk of microscopic metastases after surgery. Adjuvant (postoperative) chemotherapy improves survival from some other adenocarcinomas, and there is evidence that endometrial cancer is sensitive to cytotoxic therapy. This systematic review examines the effect of chemotherapy on survival after hysterectomy for endometrial cancer. Objectives To assess efficacy of adjuvant (postoperative) chemotherapy for endometrial cancer. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE up to August 2010, registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) comparing adjuvant chemotherapy with any other adjuvant treatment or no other treatment. Data collection and analysis We used a random-effects meta-analysis to assess hazard ratios (HR) for overall and progression-free survival and risk ratios (RR) to compare death rates and site of initial relapse. Main results Five RCTs compared no additional treatment with additional chemotherapy after hysterectomy and radiotherapy. Four trials compared platinum based combination chemotherapy directly with radiotherapy. Indiscriminate pooling of survival data from 2197 women shows a significant overall survival advantage from adjuvant chemotherapy (RR (95% CI) = 0.88 (0.79 to 0.99)). Sensitivity analysis focused on trials of modern platinum based chemotherapy regimens and found the relative risk of death to be 0.85 ((0.76 to 0.96); number needed to treat for an additional beneficial outcome (NNT) = 25; absolute risk reduction = 4% (1% to 8%)). The HR for overall survival is 0.74 (0.64 to 0.89), significantly

  4. Psychosocial and Physical Effects of Adjuvant Chemotherapy

    PubMed Central

    Hislop, Thomas Gregory; Elwood, J. Mark; Waxler-Morrison, Nancy; Ragaz, Joseph; Skippen, Diane Hazel; Turner, I.D.

    1991-01-01

    Breast cancer patients younger than 55 completed a questionnaire on psychosocial factors and physical side effects shortly after diagnosis and 9 to 15 months after diagnosis. Those who had used adjuvant chemotherapy were more likely than those who had not to report physical side effects; there was little difference in psychosocial factors. Recent users were more likely than ex-users to report physical side effects, difficulties with domestic chores, and improvement in psychosocial factors. PMID:21229020

  5. Neoadjuvant and Adjuvant Chemotherapy of Cervical Cancer.

    PubMed

    Mallmann, Peter; Mallmann, Christoph

    2016-01-01

    Neoadjuvant chemotherapy is indicated in patients who can tolerate the side effects of a chemotherapy and with preoperative presentation of one of the following clinical risk situations: bulky disease with a maximal tumor diameter of > 4 cm, suspicious lymph nodes in magnetic resonance imaging (MRI), computed tomography (CT) scan or endosonography, histopathologically confirmed lymph node metastasis, or histopathologically documented risk factors such as G3 and L1V1. A neoadjuvant chemotherapy followed by surgery should be performed with cisplatin at a dosage of > 25 mg/m2 per week and an application interval of < 14 days. The previously published data suggests an improved rate of complete resection and reduced incidences of positive lymph nodes and parametric infiltration. Accordingly, the percentage of patients in need for adjuvant radiochemotherapy after operation can be significantly reduced. Some studies demonstrated a prolongation of progression-free and overall survival. Following the previously published studies, adjuvant chemotherapy after operation or after radiochemotherapy has no significant effect on the overall survival and, following the current guidelines, should be avoided. PMID:27614740

  6. Adjuvant chemotherapy for rectal cancer: Is it needed?

    PubMed Central

    Milinis, Kristijonas; Thornton, Michael; Montazeri, Amir; Rooney, Paul S

    2015-01-01

    Adjuvant chemotherapy has become a standard treatment of advanced rectal cancer in the West. The benefits of adjuvant chemotherapy after surgery alone have been well established. However, controversy surrounds the use adjuvant chemotherapy in patients who received preoperative chemoradiotherapy, despite it being recommended by a number of international guidelines. Results of recent multicentre randomised control trials showed no benefit of adjuvant chemotherapy in terms of survival and rates of distant metastases. However, concerns exist regarding the quality of the studies including inadequate staging modalities, out-dated chemotherapeutic regimens and surgical approaches and small sample sizes. It has become evident that not all the patients respond to adjuvant chemotherapy and more personalised approach should be employed when considering the benefits of adjuvant chemotherapy. The present review discusses the strengths and weaknesses of the current evidence-base and suggests improvements for future studies. PMID:26677436

  7. Update on Adjuvant Chemotherapy for Early Breast Cancer

    PubMed Central

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

    2014-01-01

    Breast cancer is the second most common cancer in women worldwide. Although most women are diagnosed with early breast cancer, a substantial number recur due to persistent micro-metastatic disease. Systemic adjuvant chemotherapy improves outcomes and has advanced from first-generation regimens to modern dose-dense combinations. Although chemotherapy is the cornerstone of adjuvant therapy, new biomarkers are identifying patients who can forego such treatment. Neo-adjuvant therapy is a promising platform for drug development, but investigators should recognize the limitations of surrogate endpoints and clinical trials. Previous decades have focused on discovering, developing, and intensifying adjuvant chemotherapy. Future efforts should focus on customizing therapy and reducing chemotherapy for patients unlikely to benefit. In some cases, it may be possible to replace chemotherapy with treatments directed at specific genetic or molecular breast cancer subtypes. Yet, we anticipate that chemotherapy will remain a critical component of adjuvant therapy for years to come. PMID:25336961

  8. Adjuvant chemotherapy for soft tissue sarcoma.

    PubMed

    Casali, Paolo G

    2015-01-01

    Adjuvant chemotherapy is not standard treatment in soft tissue sarcoma (STS). However, when the risk of relapse is high, it is an option for shared decision making with the patient in conditions of uncertainty. This is because available evidence is conflicting, even if several randomized clinical trials have been performed for 4 decades and also have been pooled into meta-analyses. Indeed, available meta-analyses point to a benefit in the 5% to 10% range in terms of survival and distant relapse rate. Some local benefit also was suggested by some trials. Placing chemotherapy in the preoperative setting may help gain a local advantage in terms of the quality of surgical margins or decreased sequelae. This may be done within a personalized approach according to the clinical presentation. Attempts to personalize treatment on the basis of the variegated pathology and molecular biology of STS subgroups are ongoing as well, according to what is done in the medical treatment of advanced STS. Thus, decision making for adjuvant and neoadjuvant indications deserves personalization in clinical research and in clinical practice, taking profit from all multidisciplinary clinical skills available at a sarcoma reference center, though with a degree of subjectivity because of the limitations of available evidence. PMID:25993233

  9. 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

  10. Adjuvant chemotherapy in early breast cancer.

    PubMed

    Ejlertsen, Bent

    2016-05-01

    these CMF regimens has not been compared within the context of a randomised trial. Shifting from the 77B's classic CMF regimen to the 82B four-weekly IV regimen or the 89B three-weekly IV regimen was associated with a 30% increased risk of a DFS event in a multivariate analysis of a population-based cohort study. Furthermore, the four-weekly regimen used in 82B was associated with a 40% increase in mortality. The strengths of the design include identical selection criteria, uniform and prospective registration of treatment, tumour and patient characteristics. Caution is still required due to the non-experimental design of the comparison. Another finding was a substantial difference in the risk of amenorrhoea; and while 15% of patients aged 40 or younger in 77B had regular menses throughout chemotherapy, the corresponding percentage was 37 in 82B and 47 in 89B. The DBCG in collaboration with a Swedish and a Dutch centre participating in the DBCG trial 89B compared CMF with ovarian ablation in premenopausal high-risk breast cancer patients with ER-positive tumours. No significant differences were found in DFS or OS in the preplanned analysis, suggesting that the benefits of CMF may, at least in part, be explained by ovarian suppression in premenopausal patients with ER-positive tumours. However, these results are not clinically useful by themselves as other chemotherapy regimens have been more efficacious, and knowledge is still lacking regarding the benefits from adding ovarian suppression to chemotherapy plus tamoxifen. The results from the DBCG 77B and 82C are in accordance with other large adjuvant trials and the EBCTCG meta-analyses. The benefits obtained with any individual anticancer drug are largely determined by the cancer (somatic) genome; and by being a molecular target of anthracyclines, TOP2A aberrations could obviously be associated with cancer drug benefits. In the DBCG 89D, a significant heterogeneity was observed between a beneficial effect on DFS and OS

  11. Chemotherapy: Does Neoadjuvant or Adjuvant Therapy Improve Outcomes?

    PubMed

    Canter, Robert J

    2016-10-01

    Since preoperative chemotherapy has been clearly shown to improve outcomes for patients with Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma, practitioners have attempted to extend the use of adjuvant/neoadjuvant chemotherapy to other types of adult soft tissue sarcoma. Given the high risk of distant recurrence and disease-specific death for patients with soft tissue sarcoma tumors larger than 10 cm, these patients should be considered candidates for neoadjuvant chemotherapy as well as investigational therapies. Yet, potential toxicity from cytotoxic chemotherapy is substantial, and there remains little consensus and wide variation regarding the indications for use of chemotherapy in the adjuvant/neoadjuvant setting. PMID:27591503

  12. Adjuvant chemotherapy for gastric cancer: Current evidence and future challenges

    PubMed Central

    Miceli, Rosalba; Tomasello, Gianluca; Bregni, Giacomo; Di Bartolomeo, Maria; Pietrantonio, Filippo

    2014-01-01

    Gastric cancer still represents one of the major causes of cancer mortality worldwide. Patients survival is mainly related to stage, with a high proportion of patients with metastatic disease at presentation. Thus, the cure rate largely depend upon surgical resection. Despite the additional, albeit small, benefit of adjuvant chemotherapy has been clearly demonstrated, no general consensus has been reached on the best treatment option. Moreover, the narrow therapeutic index of adjuvant chemotherapy (i.e., limited survival benefit with considerable toxicity) requires a careful assessment of expected risks and benefits for individual patients. Treatment choices vary widely based on the different geographic areas, with chemotherapy alone more often preferred in Europe or Asia and chemoradiotherapy in the United States. In the present review we discuss the current evidence and future challenges regarding adjuvant chemotherapy in curatively resected gastric cancer with particular emphasis on the recently completed landmark studies and meta-analyses. The most recent patient-level meta-analysis demonstrated the benefit of adjuvant chemotherapy over curative surgery; the same Authors also showed that disease-free survival may be used as a surrogate end-point for overall survival. We finally discuss future research issues such as the need of economic evaluations, development of prognostic or predictive biomarkers, and the unmet clinical need of trials comparing perioperative chemotherapy with adjuvant treatment. PMID:24782604

  13. Adjuvant chemotherapy in elderly patients with breast cancer: key challenges.

    PubMed

    Pondé, Noam; Dal Lago, Lissandra; Azim, Hatem A

    2016-06-01

    Elderly women with early breast cancer (BC) form a heterogeneous and large subgroup (41.8% of women with BC are over 65). Decision making in this subgroup is made more difficult by lack of familiarity with their physical, cognitive and social issues. Adequate management depends on biological factors and accurate clinical evaluation through comprehensive geriatric assessment (CGA). CGA can help to better select and determine potential risks factors for patients who are candidates for adjuvant chemotherapy. It is still recently introduced in geriatric oncology and there is a lack of awareness of its importance. Available data on adjuvant chemotherapy for BC is limited but suggests it can be of benefit for well selected patients, though the risk of short and long-term toxicity is significant. Here we provide a discussion of the key practical issues in decision making in the setting of adjuvant chemotherapy for elderly BC patients. PMID:27010772

  14. 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

  15. Optimizing adjuvant chemotherapy in early-stage breast cancer.

    PubMed

    Perez, Edith; Muss, Hyman B

    2005-12-01

    Mortality in breast cancer has declined in the past decade, owing to advances in diagnosis, surgery, radiotherapy, and systemic treatments. Adjuvant chemotherapy has had a major effect on increasing survival in women with locoregional breast cancer. Like all treatments, adjuvant chemotherapy is a work in progress, and it has evolved from single oral agents to complex multidrug regimens. The choice of regimens is not without controversy, however, and several have been shown to be more effective than others, especially in patients who are at high risk for recurrence. The taxanes paclitaxel and docetaxel (Taxotere) have been shown to be effective in the adjuvant setting, and they have also been shown to improve the outcomes in node-positive disease. Both disease-free and overall survival are greater with doxorubicin, paclitaxel, and cyclophosphamide given in a dose-dense, every-2-week schedule with growth factor support than with the same agents given in an every-3-week schedule. Disease-free and overall survival in patients with node-positive disease are greater with docetaxel, doxorubicin (Adriamycin), and cyclophosphamide (TAC) than with fluorouracil, doxorubicin, and cyclophosphamide (FAC). Febrile neutropenia is common with the TAC regimen, but it can be minimized with growth factor support. Based on these findings, dose-dense therapy and TAC are the current adjuvant treatments of choice in patients with node-positive disease; other, less-intense regimens may be appropriate in patients with lower-risk disease. Ongoing trials are investigating the efficacy of commonly used regimens, new chemotherapeutic and biologic agents, and novel doses and schedules of currently available agents. PMID:16506631

  16. Adjuvant post-operative chemotherapy in bitches with mammary cancer.

    PubMed

    Karayannopoulou, M; Kaldrymidou, E; Constantinidis, T C; Dessiris, A

    2001-03-01

    The survival time in a group of eight bitches with malignant mammary tumours given adjuvant post-operative chemotherapy was compared with survival in another group of eight bitches with mammary cancer which were treated by surgical excision alone. The same surgical procedure was used in both groups. All bitches had stage III disease according to the World Health Organization clinical staging system. Histologically, 10 of the bitches had complex carcinomas (carcinomatous mixed tumours), the remaining six bitches had carcinosarcomas. The chemotherapeutic protocol used was a combination of 5-fluorouracil (150 mg/m2 of body surface area) and cyclophosphamide (100 mg/m2) given on the same day, intravenously, every week for four consecutive weeks. Chemotherapy was started one week post-surgery. Selected haematological parameters (packed cell volume, white blood cell count, platelet count and differential white blood cell count) and serum biochemical parameters (alanine aminotransferase, alkaline phosphatase, blood urea nitrogen and creatinine) were measured before and during chemotherapy. Survival analysis indicated that the chemotherapeutic regimen had a positive influence on the disease-free interval and the survival time of the eight bitches (P < 0.05). Although leucocyte numbers were significantly decreased (P < 0.001) during chemotherapy, the mean leucocyte counts remained within normal limits. Temporary leukopenia was noted only in one bitch. Packed cell volume and alkaline phosphatase increased significantly (P < 0.05) but within normal limits. Creatinine was also increased significantly (P < 0.01) but the mean creatinine concentrations were within normal limits, although in half of the bitches the concentrations occasionally rose above normal. PMID:11315572

  17. [Recent Status of Postoperative Adjuvant Chemotherapy after Completely Resected Lung Cancer].

    PubMed

    Naito, Masahito; Tsuboi, Masahiro

    2016-02-01

    Several landmark study elucidated that adjuvant cisplatin-based chemotherapy for stage II-IIIA non-small cell lung cancer (NSCLC)patients after appropriate surgical resection can significantly improve 5-year survival rate. Meta-analysis of modern cisplatin based adjuvant chemotherapy trial confirmed this benefit. Furthermore, in Japan, large randomized trial and metaanalysis assessing the efficacy of uracil-tegafur(UFT)for stage I patients with completely resected NSCLC reported that UFT can significantly improve 5-year survival rate. Meta-analysis of subgroup assessed that effectiveness of UFT for stage I NSCLC patients with a tumor lager than 2 cm. According to these evidence, cisplatin-based adjuvant chemotherapy for stage II-III A NSCLC and UFT for stage I NSCLC patients with a tumor lager than 2 cm are used standard postoperative adjuvant chemotherapy in Japan. In recent year, it is presumed that personalized care will be necessary to re-evaluate strategies for postoperative adjuvant chemotherapy of lung cancer. Considering histological subtype of lung cancer, several randomize trial for postoperative adjuvant chemotherapy with non-squamous NSCLC or high neuroendocrine tumor of lung are ongoing. In addition, recent studies of biological research indicate that some tumor marker such as ERCC1 may had a predictive value for selecting patients who will derive the benefit from adjuvant chemotherapy. PMID:27067681

  18. Magnetic nanoparticle hyperthermia as an adjuvant cancer therapy with chemotherapy

    NASA Astrophysics Data System (ADS)

    Petryk, Alicia Ailie

    Magnetic nanoparticle hyperthermia (mNPH) is an emerging cancer therapy which has shown to be most effective when applied in the adjuvant setting with chemotherapy, radiation or surgery. Although mNPH employs heat as a primary therapeutic modality, conventional heat may not be the only cytotoxic effect. As such, my studies have focused on the mechanism and use of mNPH alone and in conjunction with cisplatinum chemotherapy in murine breast cancer cells and a related in vivo model. MNPH was compared to conventional microwave tumor heating, with results suggesting that mNPH (mNP directly injected into the tumor and immediately activated) and 915 MHz microwave hyperthermia, at the same thermal dose, result in similar tumor regrowth delay kinetics. However, mNPH shows significantly less peri-tumor normal tissue damage. MNPH combined with cisplatinum also demonstrated significant improvements in regrowth delay over either modality applied as a monotherapy. Additional studies demonstrated that a relatively short tumor incubation time prior to AMF exposure (less than 10 minutes) as compared to a 4-hour incubation time, resulted in faster heating rates, but similar regrowth delays when treated to the same thermal dose. The reduction of heating rate correlated well with the observed reduction in mNP concentration in the tumor observed with 4 hour incubation. The ability to effectively deliver cytotoxic mNPs to metastatic tumors is the hope and goal of systemic mNP therapy. However, delivering relevant levels of mNP is proving to be a formidable challenge. To address this issue, I assessed the ability of cisplatinum to simultaneously treat a tumor and improve the uptake of systemically delivered mNPs. Following a cisplatinum pretreatment, systemic mNPs uptake was increased by 3.1 X, in implanted murine breast tumors. Additional in vitro studies showed the necessity of a specific mNP/ Fe architecture and spatial relation for heat-based cytotoxicity in cultured cells.

  19. Racial variation in adjuvant chemotherapy initiation among breast cancer patients receiving oncotype DX testing.

    PubMed

    Roberts, Megan C; Weinberger, Morris; Dusetzina, Stacie B; Dinan, Michaela A; Reeder-Hayes, Katherine E; Troester, Melissa A; Carey, Lisa A; Wheeler, Stephanie B

    2015-08-01

    It is unknown whether racial differences exist in adjuvant chemotherapy initiation among women with similar oncotype DX (ODX) risk scores. We examined whether adjuvant chemotherapy initiation varied by race. Data come from the Phase III, Carolina Breast Cancer Study, a longitudinal, population-based study of North Carolina women diagnosed with breast cancer between 2008 and 2014. We used modified Poisson regression and report adjusted relative risk (aRR) and 95% confidence intervals (95%CI) to estimate the association between race and adjuvant chemotherapy initiation across ODX risk groups among women who received the test (n = 541). Among women who underwent ODX testing, 54.2, 37.5, and 8.3% of women had tumors classified as low-, intermediate-, and high-risk groups, respectively. We observed no racial variation in adjuvant chemotherapy initiation. Increasing ODX risk score (aRR = 1.39, 95%CI = 1.22, 1.58) and being married (aRR = 2.92, 95%CI = 1.12, 7.60) were independently associated with an increased likelihood of adjuvant chemotherapy in the low-risk group. Among women in the intermediate-risk group, ODX risk score (aRR = 1.15, 95%CI = 1.11, 1.20), younger age (aRR = 1.95, 95%CI = 1.35, 2.81), larger tumor size (aRR = 1.70, 95%CI = 1.22, 2.35), and higher income were independently associated with increased likelihood of adjuvant chemotherapy initiation. No racial differences were found in adjuvant chemotherapy initiation among women receiving ODX testing. As treatment decision-making becomes increasingly targeted with the use of genetic technologies, these results provide evidence that test results may drive treatment in a similar way across racial subgroups. PMID:26216535

  20. Adjuvant Chemotherapy Use and Adverse Events among Older Patients with Stage III Colon Cancer

    PubMed Central

    Kahn, Katherine L.; Adams, John L.; Weeks, Jane C.; Chrischilles, Elizabeth A.; Schrag, Deborah; Ayanian, John Z.; Kiefe, Catarina I.; Ganz, Patricia A.; Bhoopalam, Nirmala; Potosky, Arnold L.; Harrington, David P.; Fletcher, Robert H.

    2010-01-01

    Context Randomized trials suggest adjuvant chemotherapy is effective for elderly patients with stage III colon cancer. However, the elderly are less likely to receive this therapy than younger patients, perhaps because of concern about adverse effects. Objective To evaluate adjuvant chemotherapy use and outcomes for older patients with stage III colon cancer from well-defined population-based settings and healthcare systems. Design Observational study of adjuvant chemotherapy use and outcomes by age, using Poisson regression to estimate the number of adverse events adjusted for demographic and clinical factors, including comorbid illness and specific elements of chemotherapy regimens documented with clinically detailed medical record reviews and patient and surrogate surveys. Setting Five geographically defined regions (Alabama, Iowa, Los Angeles County, Northern California, and North Carolina), five integrated health-care delivery systems, and 15 Veterans hospitals. Patients All 675 patients diagnosed with stage III colon cancer during 2003-2005 who underwent surgical resection were followed up to 15 months post-diagnosis. Main outcome measures Chemotherapy regimen, dose, duration and annualized mean number of adverse events stratified by age. Results Half of the 202 patients >=75 years received adjuvant chemotherapy compared with 87% of 473 younger patients (diff 37%, 95% CI 30%-45%). Among adjuvant chemotherapy users, 14 (14%) of patients >=75 years and 178 (44%) of younger patients received a regimen containing oxaliplatin (diff 30%, 95% CI 21%-38%). Older patients were less likely to continue. By 150 days, 99 (40%) patients >= 65 years and 68 (25%) younger patients had discontinued chemotherapy (diff 15%, 95% CI 7%-23%). Overall, 162 (24%) patients had at least one adverse clinical event, with more events among patients treated with vs. without adjuvant chemotherapy (mean 0.394 vs. 0.160, diff 0.234, 95% CI 0.11-0.36, p<0.001). Among adjuvant chemotherapy

  1. Adjuvant chemotherapy of axillary node-negative carcinoma of the breast using doxorubicin and cyclophosphamide.

    PubMed

    Brooks, R J; Jones, S E; Salmon, S E; Chase, E M; Davis, S L; Moon, T E; Giordano, G F; Ketchel, S J; Jackson, R A

    1986-01-01

    One hundred fifty-six women with axillary node-negative breast cancer and primary tumors less than or equal to 5 cm in diameter (T1N0 or T2N0) were treated with a brief course of postoperative adjuvant chemotherapy consisting of doxorubicin and cyclophosphamide. Treatment was well tolerated and toxicity was minimal. With a median follow-up time of 58 months, there has been 1 relapse among 58 patients with T1 primary lesions and 15 relapses among 98 patients with T2 primary tumors. When compared with a matched historical control group receiving surgery alone, significant improvement was apparent in disease-free survival among the patients who received adjuvant chemotherapy. Prospective controlled trials are needed if we are to confirm this favorable experience with adjuvant chemotherapy in the treatment of women with node-negative breast cancer. PMID:3534586

  2. Adjuvant chemotherapy in adult medulloblastoma: is it an option for average-risk patients?

    PubMed

    Franceschi, E; Bartolotti, M; Paccapelo, A; Marucci, G; Agati, R; Volpin, L; Danieli, D; Ghimenton, C; Gardiman, M P; Sturiale, C; Poggi, R; Mascarin, M; Balestrini, D; Masotto, B; Brandes, A A

    2016-06-01

    The standard treatment in children with average-risk medulloblastoma (MB) is reduced-dose radiotherapy (RT) followed by chemotherapy. However, in adults, there is no agreement on the use of adjuvant chemotherapy. We performed a retrospective analysis of adult MB patients with average-risk disease, defined as no postsurgical residual (or ≤1.5 cm(2)) and no metastatic disease (M0). Main inclusion criteria were: age >16 years, post-surgical treatment with craniospinal irradiation with or without adjuvant chemotherapy (cisplatin and etoposide ± cyclophosphamide). From 1988 to 2012 were accrued 43 average-risk MB patients treated with surgery and adjuvant RT. Fifteen (34.9 %) patients received also chemotherapy: 7 before RT, 5 after RT, and 3 before and after RT. Reasons to administer chemotherapy were presence of residual disease (even if ≤1.5 cm) and delay in RT. After a median follow up time of 10 years (range: 8-13), median survival was 18 years (95 % CI 9-28) in patients who receive RT alone, and was not reached in patients treated with RT plus chemotherapy. The survival rates at 5, 10 and 15 years were 100 %, 78.6 % (95 % CI 60.0-97.2 %) and 60.2 % (95 % CI 36.9-83.5 %), in patients treated with RT alone, and 100, 100 and 100 %, in patients treated with RT plus chemotherapy (p = 0.079). Our findings suggest a role for adjuvant chemotherapy in the treatment of average-risk MB adult patients. Further improvements might drive to add chemotherapy in average-risk setting with less favourable biological signatures (i.e., non-WNT group). PMID:26940908

  3. Is It Possible to Shorten the Duration of Adjuvant Chemotherapy for Locally Advanced Rectal Cancer?

    PubMed Central

    You, Kai-Yun; Huang, Rong; Yu, Xin; Liu, Yi-Min; Gao, Yuan-Hong

    2016-01-01

    Abstract The long duration of 4 months of postoperative adjuvant chemotherapy is currently recommended for locally advanced rectal cancer after preoperative chemoradiation and surgery. Whether a short duration could be applied in these patients is unknown. So, the purpose of this study is to evaluate the effects on prognosis based on different durations of adjuvant chemotherapy for rectal cancer. We performed a retrospective study of 200 rectal cancer patients who were treated with preoperative chemoradiation and were pathologically graded as ypII and ypIII stages between March 2003 and May 2012. All patients were divided into 2 groups according to the median duration of adjuvant chemotherapy of 2 months. Overall survival (OS) and disease-free survival (DFS) were compared between patients with duration shorter and longer than 2 months in the whole group and subgroups of ypII and ypIII. Recurrence patterns were also analyzed in all subgroups. Multivariate analysis was performed to explore clinical factors that were significantly associated with DFS, local recurrence-free survival, and distant metastasis-free survival. In subgroup of ypII stage, the 5-year OS and DFS were similar between patients in long and short durations of adjuvant chemotherapy. For patients of ypIII stage, although no significant difference was found in OS between patients in short and long durations, DFS was showed to be higher in the group of long duration. Further analysis showed that longer duration of adjuvant chemotherapy could lead to improved control of distant metastasis and no impact on local control. Multivariable analysis indicated that long duration of adjuvant chemotherapy is significantly associated with longer distant metastasis-free survival in patients with ypIII stage, but not in those with ypII stage. A long duration of at least 2 months of postoperative adjuvant chemotherapy is necessary for patients with ypIII stage, whereas it may not be absolutely appropriate for those

  4. Adjuvant chemotherapy in soft tissue sarcomas…Conflicts, consensus, and controversies

    PubMed Central

    Bajpai, Jyoti; Susan, Deepa

    2016-01-01

    Soft tissue sarcomas (STSs) are an uncommon and diverse group of more than 50 mesenchymal malignancies. Each of these histologic subtypes represents a unique disease with distinct biologic behavior and varying sensitivity to chemotherapy. The judicious use of adjuvant/neoadjuvant chemotherapy along with surgery and radiation in the treatment of localized STS has a role in improving patient outcomes by decreasing local and distant recurrences. There is evidence that the use of adjuvant chemotherapy to a mixed cohort of chemo sensitive and insensitive sarcoma subtypes results in limited benefit. Therefore, it is of paramount importance to identify the subpopulation with high metastatic potential and to identify effective histology-specific treatment options to these patients. Present perspective, will focus on the rationale for adjuvant chemotherapy in sarcoma, with emphasis on the histology driven chemotherapy. It will outline key therapeutic opportunities and hurdles in adjuvant medical treatment of sarcoma, focusing on specific subtypes that are on the verge of new breakthroughs, as well as those in which promise has not lived up to expectations. PMID:27169114

  5. Adjuvant chemotherapy in soft tissue sarcomas…Conflicts, consensus, and controversies.

    PubMed

    Bajpai, Jyoti; Susan, Deepa

    2016-01-01

    Soft tissue sarcomas (STSs) are an uncommon and diverse group of more than 50 mesenchymal malignancies. Each of these histologic subtypes represents a unique disease with distinct biologic behavior and varying sensitivity to chemotherapy. The judicious use of adjuvant/neoadjuvant chemotherapy along with surgery and radiation in the treatment of localized STS has a role in improving patient outcomes by decreasing local and distant recurrences. There is evidence that the use of adjuvant chemotherapy to a mixed cohort of chemo sensitive and insensitive sarcoma subtypes results in limited benefit. Therefore, it is of paramount importance to identify the subpopulation with high metastatic potential and to identify effective histology-specific treatment options to these patients. Present perspective, will focus on the rationale for adjuvant chemotherapy in sarcoma, with emphasis on the histology driven chemotherapy. It will outline key therapeutic opportunities and hurdles in adjuvant medical treatment of sarcoma, focusing on specific subtypes that are on the verge of new breakthroughs, as well as those in which promise has not lived up to expectations. PMID:27169114

  6. Pilot study of bone mineral density in breast cancer patients treated with adjuvant chemotherapy

    NASA Technical Reports Server (NTRS)

    Headley, J. A.; Theriault, R. L.; LeBlanc, A. D.; Vassilopoulou-Sellin, R.; Hortobagyi, G. N.

    1998-01-01

    The objective of this cross-sectional study was to determine lumbar spine bone mineral density (BMD) in breast cancer patients previously treated with adjuvant chemotherapy. Sixteen of 27 patients who received adjuvant chemotherapy became permanently amenorrheic as a result of chemotherapy. BMD was measured at the lumbar spine using dual energy X-ray absorptiometry (DEXA). Chemotherapy drugs and dosages along with a history of risk factors for reduced bone density including activity level, tobacco and/or alcohol use, metabolic bone disease, family history, and hormone exposure were identified. Results showed that women who became permanently amenorrheic as a result of chemotherapy had BMD 14% lower than women who maintained menses after chemotherapy. Chemotherapy-treated women who maintained ovarian function had normal BMD. This study suggests that women who have premature menopause as a result of chemotherapy for breast cancer are at increased risk of bone loss and may be at risk for early development of osteoporosis. Women who maintain menses do not appear to be at risk for accelerated trabecular bone loss.

  7. Palliative oxaliplatin-based chemotherapy after exposure to oxaliplatin in the adjuvant setting for colon cancer

    PubMed Central

    Kumar, Aalok; Lim, Howard John

    2015-01-01

    Background Little is known regarding the efficacy of oxaliplatin-based chemotherapy for metastatic colon cancer patients who have already received adjuvant oxaliplatin-based chemotherapy. Methods We retrospectively reviewed 22 consecutive patients who developed recurrence after adjuvant oxaliplatin-based chemotherapy for stage III colon cancer and received another course of oxaliplatin-based chemotherapy for their metastatic disease. The main endpoint was progression-free survival (PFS). Results A total of 635 patients received oxaliplatin-based chemotherapy for stage III colon cancer at the British Columbia Cancer Agency from 2006 to 2011. A total of 176 patients recurred, 22 (12.5%) of whom were re-exposed to oxaliplatin in the metastatic scenario. Oxaliplatin in combination with fluoropyrimidine was given as first, second and third line in in 3 (13.6%), 14 (63.6%), and 5 (22.7%) patients respectively. Median time from the last cycle of adjuvant oxaliplatin-based chemotherapy to the first cycle of palliative oxaliplatin-based chemotherapy was 44.3 months. Median PFS and overall survival (OS) were 3.3 (95% CI, 1.4-5.1) and 10.0 months (95% CI, 5.3-14.6), respectively. There was no difference in PFS for patients re-exposed to oxaliplatin less than 36 months compared to longer (3.6 versus 3.1 months, P=0.793, HR =0.88). Conclusions In this population-based study, only a small proportion of pts who recurred after oxaliplatin-based adjuvant therapy received oxaliplatin in the metastatic setting. Re-exposure of oxaliplatin in combination with fluoropyrimidine is associated with only modest PFS benefit. Larger studies evaluating the role of oxaliplatin re-exposure are needed. PMID:26487941

  8. Adjuvant Chemotherapy Following Complete Resection of Soft Tissue Sarcoma in Adults: A Clinical Practice Guideline

    PubMed Central

    Bramwell, Vivien H. C.; Bell, Robert; Davis, Aileen M.; Charette, Manya L.; The members of the cancer care Ontario practice guidelines initiative sarcoma disease site group

    2002-01-01

    Purpose. To review the literature and make recommendations for the use of anthracycline-based adjuvant chemotherapy in adult patients with soft tissue sarcoma (STS). Patients. The recommendations apply to patients >15 years old with completely resected STS. Methods. A systematic overview of the published literature was combined with a consensus process around the interpretation of the evidence in the context of conventional practice to develop an evidence-based practice guideline. Results. Four meta-analyses and 17 randomized clinical trials comparing anthracycline-based adjuvant chemotherapy versus observation were reviewed. The Sarcoma Meta-Analysis Collaboration (SMAC) was the best analysis because it assessed individual patient data and had the longest follow-up. The results of the SMAC meta-analysis together with data from more recently published randomized trials, as well as our analysis of the toxicity and compliance data, are incorporated in this systematic review. Discussion. It is reasonable to consider anthracycline-based adjuvant chemotherapy in patients who have had removal of a sarcoma with features predicting a high likelihood of relapse (deep location, size >5 cm, high histological grade). Although the benefits of adjuvant chemotherapy are most apparent in patients with extremity sarcomas, patients with high-risk tumours at other sites should also be considered for such therapy. PMID:18521341

  9. MYST3/CREBBP Rearranged Acute Myeloid Leukemia after Adjuvant Chemotherapy for Breast Cancer

    PubMed Central

    Patnaik, Mrinal M.; Naina, Harris V.

    2014-01-01

    Although rare, clinicians and patients must be aware that therapy related malignancies, specifically acute myeloid leukemia (AML), can occur as a complication of adjuvant chemotherapy for breast cancer. Vigilance for signs and symptoms is appropriate. AML with t (8;16) is a specific translocation leading to formation of a fusion protein (MYST3/CREBBP). The MYST3/CREBBP AML tends to develop within 2 years of adjuvant chemotherapy, especially for breast cancer, without preceding myelodysplasia. It usually presents with disseminated intravascular coagulation and osteolytic lesions and has a poor prognosis despite aggressive resuscitation and therapy. With the increasing use of adjuvant chemotherapy for breast cancer, we are seeing a definite increase in the incidence of therapy related myelodysplastic syndromes and AML. One must keep this complication in mind while counseling and following up breast cancer patients who have received adjuvant chemotherapy. New osteolytic bone lesions in a patient with history of breast cancer do not necessarily mean metastatic disease and should be fully evaluated. PMID:25548695

  10. Adjuvant chemotherapy for bladder cancer-why does level 1 evidence not support it?

    PubMed

    Raghavan, D; Bawtinhimer, A; Mahoney, J; Eckrich, S; Riggs, S

    2014-10-01

    Neoadjuvant cisplatin-based combination chemotherapy provides a 5% increase in cure rate, an increase in median survival of about 3 years, and statistically significant and clinically relevant increments in overall survival for patients with invasive bladder cancer. Despite compelling level 1 data, it has become quite clear that facts that are similar to those that changed the paradigm of treatment of breast cancer in the 1970s have not had a similar influence on patterns of practice in bladder cancer care. Instead of using this proven approach, cystectomy alone or surgery followed by adjuvant chemotherapy is often used as a functional alternative for patients with deeply invasive and/or node-metastatic disease discovered at radical cystectomy. However, there is no well-powered level 1 evidence to support routine adjuvant chemotherapy for invasive bladder cancer, and some randomized trials have shown inferior outcomes. There is a clear need for a well-designed, randomized trial that tests the utility of adjuvant chemotherapy for invasive bladder cancer, but until that has been completed, neoadjuvant chemotherapy followed by definitive local treatment should be the standard of care for invasive bladder cancer. PMID:24569916

  11. [A Case of Idiopathic Thrombocytopenic Purpura during Adjuvant Chemotherapy for Colon Cancer].

    PubMed

    Takahara, Yoshihiro; Ozawa, Shinichi; Ogasawara, Takeshi; Shida, Takashi; Nomura, Satoru; Sato, Yoshiharu; Takahashi, Makoto

    2015-11-01

    A 76-year-old man underwent surgery for sigmoid colon cancer. The pathological finding was stage Ⅱ with a high-risk of recurrence (SI [bladder], l y0, v2, pN0, H0, P0, M0). He was treated with TS-1 as adjuvant chemotherapy. After the 1 course of chemotherapy, his platelet count was 4,000/mL. The high index of platelet associated IgG (PA-IgG) and bone marrow examination suggested that thrombocytopenia was caused by idiopathic thrombocytopenic purpura. The platelet count improved by prednisolone administration and Helicobacter pylori eradication treatment. After 6 months with no administration of adjuvant chemotherapy, the colon cancer recurred locally, and we performed a Hartmann's operation. PMID:26805292

  12. Adjuvant chemotherapy is not associated with improved survival for all high-risk factors in stage II colon cancer.

    PubMed

    Verhoeff, S R; van Erning, F N; Lemmens, V E P P; de Wilt, J H W; Pruijt, J F M

    2016-07-01

    Adjuvant chemotherapy can be considered in high-risk stage II colon cancer comprising pT4, poor/undifferentiated grade, vascular invasion, emergency surgery and/or <10 evaluated lymph nodes (LNs). Adjuvant chemotherapy administration and its effect on survival was evaluated for each known risk factor. All patients with high-risk stage II colon cancer who underwent resection and were diagnosed in the Netherlands between 2008 and 2012 were included. After stratification by risk factor(s) (vascular invasion could not be included), Cox regression was used to discriminate the independent association of adjuvant chemotherapy with the probability of death. Relative survival was used to estimate disease-specific survival. A total of 4,940 of 10,935 patients with stage II colon cancer were identified as high risk, of whom 790 (16%) patients received adjuvant chemotherapy. Patients with a pT4 received adjuvant chemotherapy more often (37%). Probability of death in pT4 patients receiving chemotherapy was lower compared to non-recipients (3-year overall survival 91% vs. 73%, HR 0.43, 95% CI 0.28-0.66). The relative excess risk (RER) of dying was also lower for pT4 patients receiving chemotherapy compared to non-recipients (3-year relative survival 94% vs. 85%, RER 0.36, 95% CI 0.17-0.74). For patients with only poor/undifferentiated grade, emergency surgery or <10 LNs evaluated, no association between receipt of adjuvant chemotherapy and survival was observed. In high-risk stage II colon cancer, adjuvant chemotherapy was associated with higher survival in pT4 only. To prevent unnecessary chemotherapy-induced toxicity, further refinement of patient subgroups within stage II colon cancer who could benefit from adjuvant chemotherapy seems indicated. PMID:26914273

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

    PubMed

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

    2016-04-01

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

  14. Adjuvant chemotherapy for older adults with breast cancer: making the standard a standard.

    PubMed

    Pal, Sumanta Kumar; Mortimer, Joanne

    2009-09-01

    Muss HB, Berry DA, Cirrincione CT et al.: Adjuvant chemotherapy in older women with early-stage breast cancer. N. Engl. J. Med. 360, 2055-2065 (2009). To date, only two prospective trials evaluating adjuvant therapy for breast cancer in older adults have been published. The second and more recent trial, Cancer and Leukemia Group B (CALGB) 49907, provides substantial evidence supporting the use of standard adjuvant chemotherapy regimens (doxorubicin-cyclophosphamide or cyclophosphamide-methotrexate-5-fluorouracil) as opposed to simplified oral regimens (capecitabine). In this trial, both the risk of relapse (hazard ratio: 2.09; 95% CI: 1.38-3.17; p < 0.001) and the risk of death (hazard ratio: 1.85; 95% CI: 1.11-3.08; p = 0.02) were significantly higher with capecitabine compared with standard chemotherapy. The current review explores both the implications and potential caveats of this innovative trial. CALGB 49907 represents a paradigm for further studies of adjuvant cancer therapy in older adults. PMID:19702447

  15. The effect of immediate breast reconstruction on the timing of adjuvant chemotherapy: a systematic review.

    PubMed

    Xavier Harmeling, J; Kouwenberg, Casimir A E; Bijlard, Eveline; Burger, Koert N J; Jager, Agnes; Mureau, Marc A M

    2015-09-01

    Adjuvant chemotherapy is often needed to achieve adequate breast cancer control. The increasing popularity of immediate breast reconstruction (IBR) raises concerns that this procedure may delay the time to adjuvant chemotherapy (TTC), which may negatively impact oncological outcome. The current systematic review aims to investigate this effect. During October 2014, a systematic search for clinical studies was performed in six databases with keywords related to breast reconstruction and chemotherapy. Eligible studies met the following inclusion criteria: (1) research population consisted of women receiving therapeutic mastectomy, (2) comparison of IBR with mastectomy only groups, (3) TTC was clearly presented and mentioned as outcome measure, and (4) original studies only (e.g., cohort study, randomized controlled trial, case-control). Fourteen studies were included, representing 5270 patients who had received adjuvant chemotherapy, of whom 1942 had undergone IBR and 3328 mastectomy only. One study found a significantly shorter mean TTC of 12.6 days after IBR, four studies found a significant delay after IBR averaging 6.6-16.8 days, seven studies found no significant difference in TTC between IBR and mastectomy only, and two studies did not perform statistical analyses for comparison. In studies that measured TTC from surgery, mean TTC varied from 29 to 61 days for IBR and from 21 to 60 days for mastectomy only. This systematic review of the current literature showed that IBR does not necessarily delay the start of adjuvant chemotherapy to a clinically relevant extent, suggesting that in general IBR is a valid option for non-metastatic breast cancer patients. PMID:26285643

  16. Is adjuvant chemotherapy necessary for patients with microinvasive breast cancer after surgery?

    PubMed Central

    Niu, Hai-Fei; Wei, Li-Juan; Yu, Jin-Pu; Lian, Zhen; Zhao, Jing; Wu, Zi-Zheng; Liu, Jun-Tian

    2016-01-01

    Objective: Survival and treatment of patients with microinvasive breast cancer (MIBC) remain controversial. In this paper, we evaluated whether adjuvant chemotherapy is necessary for patients with MIBC to identify risk factors influencing its prognosis and decide the indication for adjuvant chemotherapy. Methods: In this retrospective study, 108 patients with MIBC were recruited according to seventh edition of the staging manual of the American Joint Committee on Cancer (AJCC). The subjects were divided into chemotherapy and non-chemotherapy groups. We compared the 5-year disease-free survival (DFS) and overall survival (OS) rates between groups. Furthermore, we analyzed the factors related to prognosis for patients with MIBC using univariate and multivariate analyses. We also evaluated the impact of adjuvant chemotherapy on the prognostic factors by subgroup analysis after median follow-up time of 33 months (13-104 months). Results: The 5-year DFS and OS rates for the chemotherapy group were 93.7% and 97.5%, whereas those for the non-chemotherapy group were 89.7% and 100%. Results indicate that 5-year DFS was superior, but OS was inferior, in the former group compared with the latter group. However, no statistical significance was observed in the 5-year DFS (P=0.223) or OS (P=0.530) rate of the two groups. Most relevant poor-prognostic factors were Ki-67 overexpression and negative hormonal receptors. Cumulative survival was 98.2% vs. 86.5% between low Ki-67 (≤20%) and high Ki-67 (>20%). The hazard ratio of patients with high Ki-67 was 16.585 [95% confidence interval (CI), 1.969-139.724; P=0.010]. Meanwhile, ER(-)/PR(-) patients with MIBC had cumulative survival of 79.3% compared with 97.5% for ER(+) or PR(+) patients with MIBC. The hazard ratio for ER(-)/PR(-) patients with MIBC was 19.149 (95% CI, 3.702-99.057; P<0.001). Subgroup analysis showed that chemotherapy could improve the outcomes of ER(-)/PR(-) patients (P=0.014), but not those who overexpress Ki-67

  17. Successful treatment of gallbladder mixed adenoneuroendocrine carcinoma with neo-adjuvant chemotherapy

    PubMed Central

    2012-01-01

    Mixed adenoneuroendocrine carcinoma (MANEC) carcinomas rarely occur in the gallbladder. Here we reported a case of giant gallbladder unresectable mass with local liver invasion and omentum metastasis, which proved to be neuroendocrine carcinoma (NEC) by biopsy, received successful radical operation after neo-adjuvant chemotherapy plus somatostatin treatment. The patient showed good response as the neoplasm diminished dramatically and showed clear margin after 6 courses of treatment. A radical operation including cholecystectomy, hepatic wedge resection of the gallbladder fossa segment and lymph node of group 8a and 8p resection was performed successfully. Postoperative histopathological examination revealed neuroendocrine carcinoma mixed with adenocarcinoma in the gallbladder wall. Followed up showed no evidence of recurrence after 7 months of the operation. We suggest that neo-adjuvant chemotherapy may be beneficial to gallbladder mixed neuroendocrine carcinomas in an advanced stage which could also be advantageous to NEC of other organs. Virtual slides http://www.diagnosticpathology.diagnomx.eu/vs/2731892837743787 PMID:23186166

  18. Adjuvant chemotherapy for resected colorectal cancer metastases: Literature review and meta-analysis

    PubMed Central

    Brandi, Giovanni; De Lorenzo, Stefania; Nannini, Margherita; Curti, Stefania; Ottone, Marta; Dall’Olio, Filippo Gustavo; Barbera, Maria Aurelia; Pantaleo, Maria Abbondanza; Biasco, Guido

    2016-01-01

    Surgical resection is the only option of cure for patients with metastatic colorectal cancer (CRC). However, the risk of recurrence within 18 mo after metastasectomy is around 75% and the liver is the most frequent site of relapse. The current international guidelines recommend an adjuvant therapy after surgical resection of CRC metastases despite the lower level of evidence (based on the quality of studies in this setting). However, there is still no standard treatment and the effective role of an adjuvant therapy remains controversial. The aim of this review is to report the state-of-art of systemic chemotherapy and regional chemotherapy with hepatic arterial infusion in the management of patients after resection of metastases from CRC, with a literature review and meta-analysis of the relevant randomized controlled trials. PMID:26811604

  19. Recurrent Pericarditis, an Unexpected Effect of Adjuvant Interferon Chemotherapy for Malignant Melanoma

    PubMed Central

    Marmoush, Fady; Shafi, Muhammad Ismail; Shah, Ashish

    2016-01-01

    Drug-induced pericarditis is a well-described cardiac pathology that can result from a variety of medications; however, interferon-mediated pericarditis is extremely rare. We present a case of a young female with recurrent pericarditis due to interferon therapy. The role of interferon in adjuvant chemotherapy is well known and yields good effect, but this case highlights the very uncommon phenomena of interferon induced pericarditis and the significant distress it can cause. PMID:27418981

  20. Adjuvant paclitaxel and carboplatin chemotherapy with involved field radiation in advanced endometrial cancer: A sequential approach

    SciTech Connect

    Lupe, Krystine; Kwon, Janice . E-mail: Janice.kwon@lhsc.on.ca; D'Souza, David; Gawlik, Christine; Stitt, Larry; Whiston, Frances; Nascu, Patricia; Wong, Eugene; Carey, Mark S.

    2007-01-01

    Purpose: To determine the feasibility of adjuvant paclitaxel and carboplatin chemotherapy interposed with involved field radiotherapy for women with advanced endometrial cancer. Methods and Materials: This was a prospective cohort study of women with Stage III and IV endometrial cancer. Adjuvant therapy consisted of 4 cycles of paclitaxel (175 mg/m{sup 2}) and carboplatin (350 mg/m{sup 2}) every 3 weeks, followed sequentially by external beam radiotherapy (RT) to the pelvis (45 Gy), followed by an additional two cycles of chemotherapy. Para-aortic RT and/or HDR vault brachytherapy (BT) were added at the discretion of the treating physician. Results: Thirty-three patients (median age, 63 years) received treatment between April 2002 and June 2005. Median follow-up was 21 months. Stage distribution was as follows: IIIA (21%), IIIC (70%), IVB (9%). Combination chemotherapy was successfully administered to 30 patients (91%) and 25 patients (76%), before and after RT respectively. Nine patients (27%) experienced acute Grade 3 or 4 chemotherapy toxicities. All patients completed pelvic RT; 19 (58%) received standard 4-field RT and 14 (42%) received intensity-modulated radiotherapy. Ten (30%) received extended field radiation. Four patients (12%) experienced acute Grade 3 or 4 RT toxicities. Six (18%) patients developed chronic RT toxicity. There were no treatment-related deaths. Two-year disease-free and overall survival rates were both 55%. There was only one pelvic relapse (3%). Conclusions: Adjuvant treatment with combination chemotherapy interposed with involved field radiation in advanced endometrial cancer was well tolerated. This protocol may be suitable for further evaluation in a clinical trial.

  1. [Postoperative Adjuvant Chemotherapy for Stage III Colon Cancer - Drug Selection, Tolerability, and Safety in Clinical Practice].

    PubMed

    Okada, Kazutake; Sadahiro, Sotaro; Saito, Gota; Tanaka, Akira; Suzuki, Toshiyuki

    2016-05-01

    In the National Comprehensive Cancer Network(NCCN)guidelines, oxaliplatin(L-OHP)-based chemotherapeutic regimens, including 5-fluorouracil, Leucovorin(LV), and L-OHP(FOLFOX); capecitabine and L-OHP(CapeOX); , and 5-fluorouracil, folinic acid, and L-OHP(FLOX)are designated as category 1 recommendations for postoperative adjuvant chemotherapy in Stage III colon cancer, followed by capecitabine and 5-fluorouracil plus LV as category 2A recommendations. We studied the selection of drugs for adjuvant chemotherapy and assessed the tolerability and safety of CapeOX and tegafur- uraci(l UFT)plus LV(UFT/LV)in patients with Stage III colon cancer. The study group included 104 consecutive patients with Stage III colon cancer who underwent curative surgery. One patient changed hospitals immediately after surgery. Among the remaining 103 patients, 82(80%)received adjuvant chemotherapy and 21(20%)did not. CapeOX was administered to 32 patients(31%), UFT/LV to 49 patients(48%), and capecitabine to 1 patient(1%). In 59 patients, the treatment choice was determined according to the patient's preference; 32 patient(s 54%)selected CapeOX, 26(44%)selected UFT/LV, and 1(2%) selected no chemotherapy. The treatment completion rate was 80% for CapeOX and 84% for UFT/LV. Among patients who completed chemotherapy, dose reduction and drug withdrawal were not required in 22% of patients who received CapeOX and 80% of those who received UFT/LV. Neither CapeOX nor UFT/LV was associated with any serious adverse events. The tolerability and safety of CapeOX and UFT/LV were acceptable. However, CapeOX dose had to be carefully adjusted according to each patient's condition. PMID:27210088

  2. Helicobacter pylori and gastrointestinal symptoms in diagnostics and adjuvant chemotherapy of colorectal cancer.

    PubMed

    Soveri, Leena-Maija; Osterlund, Pia; Ruotsalainen, Tarja; Poussa, Tuija; Rautelin, Hilpi; Bono, Petri

    2014-02-01

    5-Fluorouracil (5-FU)-based chemotherapy is the mainstay of adjuvant treatment for colorectal cancer (CRC). Few studies have explored Helicobacter pylori (H. pylori)-associated gastrointestinal symptoms in the diagnosis of CRC, and the association between H. pylori infection and gastrointestinal toxicity during adjuvant chemotherapy in CRC. Seventy-nine CRC patients were randomised in a prospective clinical trial to receive 5-FU and leucovorin administered as bolus injection (Mayo regimen) or continuous infusion (simplified de Gramont regimen). H. pylori antibodies were analysed at baseline, twice monthly during treatment and after treatment up to 12 months. Thirty-seven patients (47%) were H. pylori-seronegative at baseline. There was no significant association between baseline H. pylori seropositivity (n=42; 53%) and oro-gastrointestinal toxicity during chemotherapy. The median time from symptom onset of CRC to surgery was significantly longer in patients with H. pylori infection (median time, 6 vs. 5 months; P=0.012). Functional dyspeptic symptoms at presentation significantly delayed diagnosis (median time, 7.5 vs. 5 months; P=0.035), whereas anaemia, bowel symptoms, occlusion, blood in the stool, infection and hypolactasia did not. We conclude that there is no association between H. pylori status and gastrointestinal toxicity in CRC patients during chemotherapy. Dyspeptic symptoms and presence of H. pylori may delay the diagnosis of CRC. (www.controlled-trials.com/ISRCTN98405441). PMID:24396486

  3. How much survival benefit is necessary for breast cancer patients to opt for adjuvant chemotherapy? Results from a Chilean survey

    PubMed Central

    Acevedo, Francisco; Sanchez, Cesar; Jans, Jaime; Rivera, Solange; Camus, Mauricio; Besa, Pelayo

    2014-01-01

    Background: Breast cancer (BC) is the leading cause of cancer death in Chilean women. Adjuvant chemotherapy decreases recurrence and death from BC. The recommendation to indicate chemotherapy is complex. Adjuvant! Online is a valuable computational tool to predict survival benefit obtained with adjuvant systemic therapy. Previous studies in Caucasian patients with BC showed that they are willing to receive chemotherapy for a small benefit. No studies, to our knowledge, have been done in the Hispanic or Latino populations. Methods: We interviewed females with BC who had previously received adjuvant chemotherapy. Age, stage at presentation, time since last chemotherapy, type of chemotherapy, marital status, number of children, and level of education were recorded. We used the graphic representation from Adjuvant! Online to question each patient on how much survival benefit she required to accept chemotherapy. Results: There were 101 women surveyed. The average age was 55.9 (±10.2), 54.5% had involved lymph nodes, 59.4% were married, and 15.8% did not have parity; 62.3% of females accepted chemotherapy for an absolute survival benefit of 1% or less. In a multivariate analysis, younger (p = 0.02) and less-educated patients (p = 0.018) were associated with lower survival benefit required to opt for chemotherapy. Conclusion: In our study, the acceptance of chemotherapy by the Hispanic population requires minimal survival benefit and is in agreement with the Caucasian population reported elsewhere. To our knowledge, our report is the first study that evaluates the perception of Latino patients regarding the benefit of chemotherapy in early BC. PMID:24678346

  4. Long-term outcome of adjuvant chemotherapy cyclophosphamide, mitoxantrone, and fluorouracil in women with breast cancer.

    PubMed

    Kumpulainen, Eero J; Hirvikoski, Pasi P; Johansson, Risto T

    2008-01-01

    The aim of the study is to report the long-term outcome and secondary tumours of early breast cancer patients of adjuvant CNF (cyclophosphamide, mitoxantrone, and 5-fluorouracil) chemotherapy. One hundred and ninety four patients, 185 primary early breast cancer and nine locoregionally recurrent breast cancer patients, were entered onto the trial between May 1986 and November 1993. The therapies included surgery, radiation therapy, adjuvant CNF chemotherapy, and tamoxifen according to hormonal status. Some of patients were treated twice with CMF (methotrexate). The median follow-up time was 12.9 years. Eighty nine (48%) primary breast cancers relapsed, and six locoregional breast cancers relapsed. After 5-10 years the relapse incidence decreased notably. Eighty three patients died of breast cancer, and nine of other causes. Two cases of leukemia, six cases of skin cancer, two cases of Hodgkin's disease, two cases of meningioma, and two cases of endometrial cancer were observed. This article confirms the feasibility of adjuvant CNF for early breast cancer patients. Questions of possible causability of secondary cancer have yet to be explored. PMID:18097780

  5. Surgery and Adjuvant Chemotherapy Use Among Veterans With Colon Cancer: Insights From a California Study

    PubMed Central

    Hynes, Denise M.; Tarlov, Elizabeth; Durazo-Arvizu, Ramon; Perrin, Ruth; Zhang, Qiuying; Weichle, Thomas; Ferreira, M. Rosario; Lee, Todd; Benson, Al B.; Bhoopalam, Nirmala; Bennett, Charles L.

    2010-01-01

    Purpose US veterans have been shown to be a vulnerable population with high cancer rates, and cancer care quality in Veterans Affairs (VA) hospitals is the focus of a congressionally mandated review. We examined rates of surgery and chemotherapy use among veterans with colon cancer at VA and non-VA facilities in California to gain insight into factors associated with quality of cancer care. Methods A retrospective cohort of incident colon cancer patients from the California Cancer Registry, who were ≥ 66 years old and eligible to use VA and Medicare between 1999 and 2001, were observed for 6 months after diagnosis. Results Among 601 veterans with colon cancer, 72% were initially diagnosed and treated in non-VA facilities. Among veterans with stage I to III cancer, those diagnosed and initially treated in VA facilities experienced similar colectomy rates as those at non-VA facilities. Stage III patients diagnosed and initially treated in VA versus non-VA facilities had similar odds of receiving adjuvant chemotherapy. In both settings, older patients had lower odds of receiving chemotherapy than their younger counterparts even when race and comorbidity were considered (age 76 to 85 years: odds ratio [OR] = 0.18; 95% CI, 0.07 to 0.46; age ≥ 86 years: OR = 0.17; 95% CI, 0.04 to 0.73). Conclusion In California, older veterans with colon cancer used both VA and non-VA facilities for cancer treatment, and odds of receiving cancer-directed surgery and chemotherapy were similar in both systems. Among stage III patients, older age lowered odds of receiving adjuvant chemotherapy in both systems. Further studies should continue to explore potential health system effects on quality of colon cancer care across the United States. PMID:20406940

  6. Differential clonal evolution in oesophageal cancers in response to neo-adjuvant chemotherapy

    PubMed Central

    Findlay, John M.; Castro-Giner, Francesc; Makino, Seiko; Rayner, Emily; Kartsonaki, Christiana; Cross, William; Kovac, Michal; Ulahannan, Danny; Palles, Claire; Gillies, Richard S.; MacGregor, Thomas P.; Church, David; Maynard, Nicholas D.; Buffa, Francesca; Cazier, Jean-Baptiste; Graham, Trevor A.; Wang, Lai-Mun; Sharma, Ricky A.; Middleton, Mark; Tomlinson, Ian

    2016-01-01

    How chemotherapy affects carcinoma genomes is largely unknown. Here we report whole-exome and deep sequencing of 30 paired oesophageal adenocarcinomas sampled before and after neo-adjuvant chemotherapy. Most, but not all, good responders pass through genetic bottlenecks, a feature associated with higher mutation burden pre-treatment. Some poor responders pass through bottlenecks, but re-grow by the time of surgical resection, suggesting a missed therapeutic opportunity. Cancers often show major changes in driver mutation presence or frequency after treatment, owing to outgrowth persistence or loss of sub-clones, copy number changes, polyclonality and/or spatial genetic heterogeneity. Post-therapy mutation spectrum shifts are also common, particularly C>A and TT>CT changes in good responders or bottleneckers. Post-treatment samples may also acquire mutations in known cancer driver genes (for example, SF3B1, TAF1 and CCND2) that are absent from the paired pre-treatment sample. Neo-adjuvant chemotherapy can rapidly and profoundly affect the oesophageal adenocarcinoma genome. Monitoring molecular changes during treatment may be clinically useful. PMID:27045317

  7. [A Case of Nasopharyngeal Cancer with Febrile Neutropenia Followed by Death during Adjuvant Chemotherapy].

    PubMed

    Nakahara, Susumu; Kitamura, Koji; Honma, Keiichiro; Yamamoto, Yoshifumi; Takenaka, Yukinori; Yasui, Toshimichi; Hanamoto, Atsushi; Morii, Eiichi; Inohara, Hidenori

    2015-06-01

    Chemotherapy-related death can occur, but is rarely experienced in the case of head and neck cancer. In this report, we present the case of a 55-year-old male who died of a severe febrile neutropenia during adjuvant chemotherapy. He was initially diagnosed as having nasopharyngeal carcinoma (cT2N0M0), and concurrent chemoradiotherapy was used as a primary treatment. He did not show any critical side effects during that therapy. After residual disease was proven by biopsy, docetaxel, cisplatin and 5-fluorouracil (TPF) therapy was introduced as adjuvant chemotherapy. The patient developed a high fever with a decreased neutrophil count on day 8, and went into a state of shock on day 9. He underwent immediate systemic management, but methicillin-resistant Staphylococcus aureus (MRSA) pneumonia and enteritis were uncontrolled, resulting in death on day 43. The autopsy findings suggested that the main cause of death was acute respiratory distress syndrome (ARDS), but cytomegalovirus (CMV) infection was also noted in multiple organs. . Since it is assumed from literature that the mortality rate in TPF therapy is about 2-4%, it was considered that prior sufficient explanations and informed consent should be required before this therapy. PMID:26336750

  8. [Surgical resection with adjuvant chemotherapy for locally advanced Masaoka stage IVa thymoma; report of a case].

    PubMed

    Takeshige, Mariko; Aoki, Tadashi; Motono, Nozomu; Shimada, Koji; Nakayama, Takashi; Yazawa, Masatomo

    2010-03-01

    A 39-year-old woman was presented with a mediastinal tumor and some pleural tumors. A computed tomography (CT)-guided needle biopsy of the pleural tumor was undertaken which showed thymoma, type B1 according to the World Health Organization classification. She had underwent extended-thymectomy and resection of all pleural tumors. Histopathology confirmed these lesions to be type B2 thymoma and pleural dissemination. She received adjuvant chemotherapy. Two years after surgery the patient is alive without recurrence. PMID:20214360

  9. [A Case of Urachal Carcinoma Treated by TS-1/CDDP as Adjuvant Chemotherapy].

    PubMed

    Inoue, Katsuki; Shimada, Makoto; Saito, Katsuyuki; Ogawa, Yuuichiro; Matsubara, Eiji; Matsumoto, Yuuki; Keiichiro, Hayashi

    2015-11-01

    A 49-year-old female presented complaining of gross hematuria. Cystoscopy and magnetic resonance imaging revealed a papillary tumor on the bladder dome. At biopsy pathology the tumor was diagnosed as adenocarcinoma. We diagnosed the tumor as urachal adenocarcinoma and performed partial cystectomy of bladder dome with en-bloc resection of the urachal ligament up to the umbilicus. In surgical pathology, the tumor had invaded to the fat tissue around the urachal ligament with metastasis to the lymph node. Therefore the tumor was diagnosed as a stage IVA (Sheldon's category) urachal adenocarcinoma. After surgery, 6 cycles of chemotherapy with TS-1 and cisplatin (CDDP) were performed. There has been no relapse 5 years after surgery. This is the first report of successful adjuvant chemotherapy with TS-1/CDDP for advanced urachal adenocarcinoma. PMID:26699888

  10. Should all patients with serous and clear cell endometrial carcinoma receive adjuvant chemotherapy?

    PubMed

    Boren, Todd P; Miller, David S

    2010-11-01

    Uterine papillary serous carcinoma (UPSC) and uterine clear cell carcinoma (UCCC) represent two rare subtypes that have an increased risk of recurrence and worse overall survival compared with the more common endometrioid endometrial cancers. Meaningful data in the form of prospective randomized trials is lacking for both advanced and early-stage UPSC and UCCC. Data extrapolated from prospective trials in advanced endometrioid endometrial cancer and retrospective trials on early-stage UPSC suggest that adjuvant platinum and taxane-based chemotherapy may provide a survival benefit for these patients. Future trials specifically examining UPSC and UCCC are needed to elucidate the optimal treatment regimen for these patients. Given the current data, the option of chemotherapy should be considered in treatment-planning discussions for all patients with UPSC and UCCC. PMID:21118038

  11. In Vitro Adenosine Triphosphate-Based Chemotherapy Response Assay as a Predictor of Clinical Response to Fluorouracil-Based Adjuvant Chemotherapy in Stage II Colorectal Cancer

    PubMed Central

    Kwon, Hye Youn; Kim, Im-kyung; Kang, Jeonghyun; Sohn, Seung-Kook; Lee, Kang Young

    2016-01-01

    Purpose We evaluated the usefulness of the in vitro adenosine triphosphate-based chemotherapy response assay (ATP-CRA) for prediction of clinical response to fluorouracil-based adjuvant chemotherapy in stage II colorectal cancer. Materials and Methods Tumor specimens of 86 patients with pathologically confirmed stage II colorectal adenocarcinoma were tested for chemosensitivity to fluorouracil. Chemosensitivity was determined by cell death rate (CDR) of drug-exposed cells, calculated by comparing the intracellular ATP level with that of untreated controls. Results Among the 86 enrolled patients who underwent radical surgery followed by fluorouracil-based adjuvant chemotherapy, recurrence was found in 11 patients (12.7%). The CDR ≥ 20% group was associated with better disease-free survival than the CDR < 20% group (89.4% vs. 70.1%, p=0.027). Multivariate analysis showed that CDR < 20% and T4 stage were poor prognostic factors for disease-free survival after fluorouracil-based adjuvant chemotherapy. Conclusion In stage II colorectal cancer, the in vitro ATP-CRA may be useful in identifying patients likely to benefit from fluorouracil-based adjuvant chemotherapy. PMID:26511802

  12. GALNT14 Genotype Predicts Postoperative Outcome of Stage III Colorectal Cancer With Oxaliplatin as Adjuvant Chemotherapy

    PubMed Central

    Lin, Wey-Ran; Chiang, Jy-Ming; Liang, Kung-Hao; Lim, Siew-Na; Lai, Ming-Wei; Tsou, Yung-Kuan; Hsieh, Tzu-Yun; Hsu, Chih-Kai; Yeh, Chau-Ting

    2016-01-01

    Abstract Adjuvant oxaliplatin-based chemotherapy is widely used for stage III colorectal cancer (CRC) after curative surgery. CRC is a molecularly heterogeneous disease, and our current knowledge of therapeutic response-related genetic factors remains limited. N-acetylgalactosaminyltransferase 14 (GALNT14)-rs9679162 genotype is a prognostic predictor for chemotherapy response in advanced hepatocellular carcinoma. Here, we investigated whether this genotype was related to the therapeutic outcome of stage III CRC. A cohort of 300 stage III CRC patients receiving curative resection followed by oxaliplatin-based chemotherapy was retrospectively recruited. GALNT14 genotypes and the clinicopathological factors were correlated with posttherapeutic prognosis. Of these patients, 18% patients had GALNT14-rs9679162 “TT” and 82% had the “GT” + “GG” genotypes. The analysis showed that the “TT” genotype was associated with unfavorable overall survival (OS, P = 0.009) but not with recurrence-free survival (RFS, P = 0.700). The subgroup analysis showed that the “TT” genotype was associated with unfavorable OS in the following subgroups: age ≤65 years, men, left side CRC, N2 stage, carcinoembryonic antigen >5 ng/mL, and mucinous histology (P = 0.012, 0.011, 0.009, 0.025, 0.013, and 0.007, respectively). Within the latter 2 subgroups, the “TT” genotype was the only independent predictor for OS. Finally, the “TT” genotype was associated with the T4 tumor stage (P = 0.017) and in patients with T4 tumors, the “TT” genotype was the only independent predictor for unfavorable RFS (P = 0.007). GALNT14 “TT” genotype was associated with unfavorable OS in stage III CRC patients receiving curative surgery and adjuvant oxaliplatin-based chemotherapy. PMID:27124048

  13. [Adjuvant chemotherapy].

    PubMed

    Del Nero, A; Mandressi, A; Longo, G; Cogni, M; Mangiarotti, B; Buzzetti, V; Russo, R

    1991-06-01

    The authors treated 10 advanced renal cell carcinoma with circadian venous continuous infusion of 5-Fluoro 2-Deoxyuridine (FUDR). The drug was delivered by Medtronic Synchromed implantable pump in 14-day cycles alternating with 14-day intervals of physiologic saline infusion. Of the patient observed for at least 8 months (range: 8-32, median: 22.1) 1 showed progression. Circadian continuous central venous infusion of FUDR is minimally toxic. The FUDR can be delivered safely and conveniently in this way for long spans. This therapy is administrated in on entirely out patient setting, and associated with a normal quality of life. PMID:1830673

  14. [Integrative management of operation, perioperative rehabilitation and postoperative adjuvant chemotherapy in elderly patients with colorectal carcinoma].

    PubMed

    Xu, Dong; Jiao, Yurong; Ding, Kefeng

    2016-05-25

    With the aging of the Chinese population, it seems obvious that the number of elderly patients with the disease of colorectal carcinoma grows significantly. Meanwhile, no evidence-based practical guideline for the treatment of colorectal carcinoma are available in this particular age group. Therefore, the concept of integrative management has been brought up by the Colorectal Cancer Center of the Second Affiliated Hospital of Zhejiang University, which combines the processes of surgery, perioperative rehabilitation and adjuvant chemotherapy together. In this way, the cooperation and complementarity between different clinical departments could cooperate and complete tasks together to integrate the treatment processes into a cohesive one. To achieve the goal of integrative management, the project is divided into horizontal and vertical aspects. The horizontal integration means the cooperation between different clinical departments, which is also known as multi-discipline treatment (MDT). The vertical integration reflects the completeness of the entire treatment under the goal of consistency, strictness and job separation, which could also be explained as the clinical pathway. Furthermore, this review stresses on the integrative strategy of both clinical and biochemical indexes rehabilitation, as well as the operation and postoperative adjuvant chemotherapy which has been put in execution several years by the Colorectal Cancer Center of the Second Affiliated Hospital of Zhejiang University. PMID:27215515

  15. The Nature and Severity of Cognitive Impairment Associated with Adjuvant Chemotherapy in Women with Breast Cancer: A Meta-Analysis of the Current Literature

    ERIC Educational Resources Information Center

    Falleti, Marina G.; Sanfilippo, Antonietta; Maruff, Paul; Weih, LeAnn; Phillips, Kelly-Anne

    2005-01-01

    Objective: Several studies have identified that adjuvant chemotherapy for breast cancer is associated with cognitive impairment; however, the magnitude of this impairment is unclear. This study assessed the severity and nature of cognitive impairment associated with adjuvant chemotherapy by conducting a meta-analysis of the published literature to…

  16. Impact of Pattern Recognition Receptors on the Prognosis of Breast Cancer Patients Undergoing Adjuvant Chemotherapy.

    PubMed

    Vacchelli, Erika; Enot, David P; Pietrocola, Federico; Zitvogel, Laurence; Kroemer, Guido

    2016-06-01

    Pattern recognition receptors allow the innate immune system to perceive the presence of microbial products and to launch the first steps of the defense response. Some pattern recognition receptors also sense endogenous ligands that are released from uninfected dying cells, thereby activating immune responses against dead-cell antigens. This applies to toll-like receptors 3 and 4 (TLR3, TLR4), which sense double-stranded RNA and high-mobility group protein B1 (HMGB1), respectively, as well as to formyl peptide receptor-1 (FPR1), which interacts with Annexin A1 (ANXA1) from dead cells. Breast cancer patients who bear loss-of-function alleles in TLR3, TLR4, and FPR1 exhibit a reduced metastasis-free and overall survival after treatment with anthracycline-based adjuvant chemotherapy. These genetic defects are epistatic with respect to each other, suggesting that they act on the same pathway, linking chemotherapy to a therapeutically relevant anticancer immune response. Loss-of-function alleles in TLR4 and FPR1 also affect the prognosis of colorectal cancer patients treated with oxaliplatin-based chemotherapy. Altogether, these results support the idea that conventional anticancer treatments rely on stimulation of anticancer immune responses to become fully efficient. Cancer Res; 76(11); 3122-6. ©2016 AACR. PMID:27197163

  17. Economic Evaluation of First-Line Adjuvant Chemotherapies for Resectable Gastric Cancer Patients in China

    PubMed Central

    Tan, Chongqing; Peng, Liubao; Zeng, Xiaohui; Li, Jianhe; Wan, Xiaomin; Chen, Gannong; Yi, Lidan; Luo, Xia; Zhao, Ziying

    2013-01-01

    Background First-line postoperative adjuvant chemotherapies with S-1 and capecitabine and oxaliplatin (XELOX) were first recommended for resectable gastric cancer patients in the 2010 and 2011 Chinese NCCN Clinical Practice Guidelines in Oncology: Gastric Cancer; however, their economic impact in China is unknown. Objective The aim of this study was to compare the cost-effectiveness of adjuvant chemotherapy with XELOX, with S-1 and no treatment after a gastrectomy with extended (D2) lymph-node dissection among patients with stage II-IIIB gastric cancer. Methods A Markov model, based on data from two clinical phase III trials, was developed to analyse the cost-effectiveness of patients in the XELOX group, S-1 group and surgery only (SO) group. The costs were estimated from the perspective of Chinese healthcare system. The utilities were assumed on the basis of previously published reports. Costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICER) were calculated with a lifetime horizon. One-way and probabilistic sensitivity analyses were performed. Results For the base case, XELOX had the lowest total cost ($44,568) and cost-effectiveness ratio ($7,360/QALY). The relative scenario analyses showed that SO was dominated by XELOX and the ICERs of S-1 was $58,843/QALY compared with XELOX. The one-way sensitivity analysis showed that the most influential parameter was the utility of disease-free survival. The probabilistic sensitivity analysis predicted a 75.8% likelihood that the ICER for XELOX would be less than $13,527 compared with S-1. When ICER was more than $38,000, the likelihood of cost-effectiveness achieved by S-1 group was greater than 50%. Conclusions Our results suggest that for patients in China with resectable disease, first-line adjuvant chemotherapy with XELOX after a D2 gastrectomy is a best option comparing with S-1 and SO in view of our current study. In addition, S-1 might be a better choice, especially with a

  18. Influence of definitive radiation therapy for primary breast cancer on ability to deliver adjuvant chemotherapy

    SciTech Connect

    Lippman, M.E.; Edwards, B.K.; Findlay, P.; Danforth, D.W. Jr.; MacDonald, H.; D'Angelo, T.; Gorrell, C.

    1986-01-01

    Primary radiotherapy as a means of managing stage I and II breast cancer is receiving increasing attention. In a prospectively randomized trial comparing modified radical mastectomy to lumpectomy followed by definitive radiotherapy, we evaluated whether radiotherapy has a deleterious effect on the ability to administer adjuvant doxorubicin and cyclophosphamide to patients with histologically positive axillary lymph nodes. All patients were treated with an identical regimen, and doses were escalated to the same degree until myelosuppression occurred. There were no significant differences in the amount of chemotherapy administered to either treatment group. Patients in both groups received approximately 100% of the predicted dose of doxorubicin and approximately 117% of the predicted dose of cyclophosphamide. At present, we have no evidence that there are differences in recurrence rates as a function of the quantity of drug received, although longer follow-up is required.

  19. Is distance to chemotherapy an obstacle to adjuvant care among the N.C. Medicaid—enrolled colon cancer patients?

    PubMed Central

    Song, Eunyoung; Klepin, Heidi D.; Foley, Kristie L.

    2016-01-01

    Background Adjuvant chemotherapy for colon cancer has been linked to patient and provider characteristics but little is known about whether distance to chemotherapy providers constitutes an obstacle to chemotherapy. Methods A total of 1,184 Medicaid patients diagnosed with colon cancer in North Carolina in 1999–2002 comprised the sample. Data from the N.C. Central Cancer Registry, N.C. Medicaid Claims, American Hospital Directory and US Census were merged. Logistic regression models were used to estimate the association between chemotherapy receipt and the distance to nearest chemotherapy provider. Results Compared to the referent group of SEER-staged II (local) cancer patients living less than 2 miles from the nearest chemotherapy provider, the odds of receiving chemotherapy fell as the distance to the nearest provider increased. The odds ratio (OR) for those living ≥5 to <15 miles away was 0.13 [95% confidence intervals (CI), 0.04–0.39], and OR for those living ≥15 miles away was 0.06 (95% CI, 0.01–0.52). Patients diagnosed with regional, SEER-staged III (regional) cancer were less likely to receive chemotherapy if they lived in rural areas more than 20 miles away from the nearest provider (OR =0.08; 95% CI, 0.01–0.72). However, we found no evidence of association between chemotherapy receipt and distance to the nearest provider for regional cancer patients living in urban areas and those living in rural areas within 20 miles from the nearest chemotherapy provider. Conclusions Distance to provider may be an obstacle to chemotherapy for some groups of low-income colon cancer patients. Relieving travel burdens of rural patients living far from providers may help Medicaid increase guideline-consistent adjuvant care for regional cancer patients. PMID:27284464

  20. EMX2 Is a Predictive Marker for Adjuvant Chemotherapy in Lung Squamous Cell Carcinomas

    PubMed Central

    Zhang, Yi; Tolani, Bhairavi; Mo, Minli; Zhang, Hua; Zheng, Qingfeng; Yang, Yue; Cheng, Runfen; Jin, Joy Q.; Luh, Thomas W.; Yang, Cathryn; Tseng, Hsin-Hui K.; Giroux-Leprieur, Etienne; Woodard, Gavitt A.; Hao, Xishan; Wang, Changli; Jablons, David M.; He, Biao

    2015-01-01

    Background Squamous cell carcinomas (SCC) account for approximately 30% of non-small cell lung cancer (NSCLC). Current staging methods do not adequately predict outcome for this disease. EMX2 is a homeo-domain containing transcription factor known to regulate a key developmental pathway. This study assessed the significance of EMX2 as a prognostic and predictive marker for resectable lung SCC. Methods Two independent cohorts of patients with lung SCC undergoing surgical resection were studied. EMX2 protein expression was examined by immunohistochemistry, Western blot, or immunofluorescence. EMX2 expression levels in tissue specimens were scored and correlated with patient outcomes. Chemo-sensitivity of lung SCC cell lines stably transfected with EMX2 shRNAs to cisplatin, carboplatin, and docetaxel was examined in vitro. Results EMX2 expression was down-regulated in lung SCC tissue samples compared to their matched adjacent normal tissues. Positive EMX2 expression was significantly associated with improved overall survival in stage I lung SCC patients, and in stage II/IIIA lung SCC patients receiving adjuvant chemotherapy. EMX2 expression was also associated with expression of EMT markers in both lung SCC cell lines and tissue samples. Knock-down of EMX2 expression in lung SCC cells promoted chemo-resistance and cell migration. Conclusions EMX2 expression is down-regulated in lung SCC and its down-regulation is associated with chemo-resistance in lung SCC cells, possibly through regulation of Epithelial-to-Mesenchymal Transition (EMT). EMX2 may serve as a novel prognostic marker for stage I lung SCC patients and a prediction marker for stage II/IIIA lung SCC patients receiving adjuvant chemotherapy. PMID:26132438

  1. Cardiac Monitoring During Adjuvant Trastuzumab-Based Chemotherapy Among Older Patients With Breast Cancer

    PubMed Central

    Chavez-MacGregor, Mariana; Niu, Jiangong; Zhang, Ning; Elting, Linda S.; Smith, Benjamin D.; Banchs, Jose; Hortobagyi, Gabriel N.; Giordano, Sharon H.

    2015-01-01

    Purpose Patients treated with adjuvant trastuzumab require adequate cardiac monitoring. We describe the patterns of cardiac monitoring and evaluate factors associated with adequate monitoring in a large population-based study of older patients with breast cancer. Patients and Methods Patients age 66 years or older with full Medicare coverage, diagnosed with stage I to III breast cancer between 2005 and 2009, and treated with adjuvant trastuzumab-based chemotherapy were identified in the SEER-Medicare and the Texas Cancer Registry-Medicare databases. The adequacy of cardiac monitoring was determined. Chemotherapy, trastuzumab use, cardiac monitoring, and comorbidities were identified by using International Classification of Diseases, 9th revision and Healthcare Common Procedure Coding System codes. Prescribing physician characteristics were also evaluated. Analyses included descriptive statistics and multilevel logistic regression models. Results In all, 2,203 patients were identified; median age was 72 years. Adequate monitoring was identified in only 36.0% of the patients (n = 793). In the multivariable model, factors associated with optimal cardiac monitoring included a more recent year of diagnosis (hazard ratio [HR], 1.83; 95% CI, 1.32 to 2.54), anthracycline use (HR, 1.39; 95% CI, 1.14 to 1.71), female prescribing physician (HR, 1.37; 95% CI, 1.10 to 1.70), and physician graduating after 1990 (HR, 1.66; 95% CI, 1.29 to 2.12). The presence of cardiac comorbidities was not a determinant for cardiac monitoring. Of the variance in the adequacy of cardiac monitoring, 15.3% was attributable to physician factors and 5.2% to measured patient factors. Conclusion A large proportion of patients had suboptimal cardiac monitoring. Physician characteristics had more influence than measured patient-level factors in the adequacy of cardiac monitoring. Because trastuzumab-related cardiotoxicity is reversible, efforts to improve the adequacy of cardiac monitoring are needed

  2. Adjuvant chemotherapy after primary treatments for cervical cancer: a critical point of view and review of the literature.

    PubMed

    Angioli, Roberto; Luvero, Daniela; Aloisi, Alessia; Capriglione, Stella; Gennari, Paolo; Linciano, Francesca; Li Destri, Marta; Scaletta, Giuseppe; Montera, Roberto; Plotti, Francesco

    2014-04-01

    Cervical cancer is the second most frequent female malignancy worldwide. Concurrent chemoradiotherapy represents the standard of care for patients with advanced stage cervical cancer, while radical surgery (RS) and radiotherapy is widely used for treating early stage cervical cancer. However, the poor control of micrometastasis, declining operability, the lack of radiotherapy departments and the high incidence of long-term complications due to radiotherapy have brought about the development of different therapeutic approaches such as neoadjuvant chemotherapy followed by RS. Unfortunately, treatment results are still unsatisfactory due to a high recurrence rate and several authors have studied the possibility to add an adjuvant treatment to primary therapy. We reviewed the literature concerning the role of adjuvant chemotherapy in advanced cervical cancer after neoadjuvant chemotherapy followed by RS and after chemoradiotherapy. PMID:24483847

  3. Metronomic Adjuvant Chemotherapy Improves Treatment Outcome in Nasopharyngeal Carcinoma Patients With Postradiation Persistently Detectable Plasma Epstein-Barr Virus Deoxyribonucleic Acid

    SciTech Connect

    Twu, Chih-Wen; Wang, Wen-Yi; Chen, Chien-Chih; Liang, Kai-Li; Jiang, Rong-San; Wu, Ching-Te; Shih, Yi-Ting; Lin, Po-Ju; Liu, Yi-Chun; Lin, Jin-Ching

    2014-05-01

    Purpose: To investigate the effects of adjuvant chemotherapy in nasopharyngeal carcinoma (NPC) patients with persistently detectable plasma Epstein-Barr virus DNA (pEBV DNA) after curative radiation therapy plus induction/concurrent chemotherapy. Methods and Materials: The study population consisted of 625 NPC patients with available pEBV DNA levels before and after treatment. Eighty-five patients with persistently detectable pEBV DNA after 1 week of completing radiation therapy were eligible for this retrospective study. Of the 85 patients, 33 were administered adjuvant chemotherapy consisting of oral tegafur-uracil (2 capsules twice daily) for 12 months with (n=4) or without (n=29) preceding intravenous chemotherapy of mitomycin-C, epirubicin, and cisplatin. The remaining 52 patients who did not receive adjuvant chemotherapy served as the control group. Results: Baseline patient characteristics at diagnosis (age, sex, pathologic type, performance status, T classification, N classification, and overall stage), as well as previous treatment modality, were comparable in both arms. After a median follow-up of 70 months for surviving patients, 45.5% (15 of 33 patients) with adjuvant chemotherapy and 71.2% (37 of 52 patients) without adjuvant chemotherapy experienced tumor relapses (P=.0323). There were a significant reduction in distant failure (P=.0034) but not in local or regional recurrence. The 5-year overall survival rate was 71.6% for patients with adjuvant chemotherapy and 28.7% for patients without adjuvant chemotherapy (hazard ratio 0.27; 95% confidence interval 0.17-0.55; P<.0001). Conclusions: Our retrospective data showed that adjuvant chemotherapy can reduce distant failure and improve overall survival in NPC patients with persistently detectable pEBV DNA after curative radiation therapy plus induction/concurrent chemotherapy.

  4. Intensified Adjuvant IFADIC Chemotherapy for Adult Soft Tissue Sarcoma: A Prospective Randomized Feasibility Trial

    PubMed Central

    Brodowicz, Thomas; Schwameis, Eva; Widder, Joachim; Amann, Gabriele; Wiltschke, Christoph; Dominkus, Martin; Windhager, Reinhard; Ritschl, Peter; Pötter, Richard; Kotz, Rainer

    2000-01-01

    Purpose. The present prospective randomized adjuvant trial was carried out to compare the toxicity, feasibility and efficacy of augmented chemotherapy added to hyperfractionated accelerated radiotherapy after wide or marginal resection of grade 2 and grade 3 soft tissue sarcoma (STS). Patients and methods. Fifty-nine patients underwent primary surgery by wide or marginal excision and were subsequently randomized to receive radiotherapy alone or under the addition of six courses of ifosfamide (1500 mg/m2 , days 1–4), dacarbazine (DTIC) (200 mg/m2 , days 1–4) and doxorubicin (25 mg/m2 , days 1–2) administered in 14-day-intervals supported by granulocyte-colony stimulating factor (30 × 106 IU/day, s.c.) on days 5–13. According to the randomization protocol, 28 patients received radiotherapy only, whereas 31 patients were treated with additional chemotherapy. Results. The relative ifosfamide–doxorubicin–DTIC (IFADIC) dose intensity achieved was 93%. After a mean observation period of 41±19.7 months (range, 8.1–84 months), 16 patients (57%) in the control group versus 24 patients (77%) in the chemotherapy group were free of disease (p>0.05).Within the control group, tumor relapses occurred in 12 patients (43%;six patients with distant metastases, two with local relapse, four with both) versus seven patients (23%; five patients with distant metastases, one with local recurrence, one with both) from the chemotherapy group. Relapse-free survival (RFS) (p=0.1), time to local failure (TLF) (p=0.09), time to distant failure (TDF) (p=0.17) as well as overall survival (OS) (p=0.4) did not differ significantly between the two treatment groups. Treatment-related toxicity was generally mild in both treatment arms. Conclusion. We conclude that the safety profile of intensified IFADIC added to radiotherapy was manageable and tolerable in the current setting. Inclusion of intensified IFADIC was not translated into a significant benefit concerning OS, RFS, TLF and

  5. Association of osteoprotegerin and bone loss after adjuvant chemotherapy in early-stage breast cancer

    PubMed Central

    Oostra, Drew R.; Lustberg, Maryam B.; Reinbolt, Raquel E.; Pan, Xueliang; Wesolowski, Robert; Shapiro, Charles L.

    2015-01-01

    Purpose Chemotherapy induced ovarian failure (CIOF) results in rapid bone loss. Receptor Activator of Nuclear Factor Kappa-B (RANK)-RANK ligand (RANK-L) signaling balances bone resorption and formation. Osteoprotegerin (OPG) acts as a decoy receptor for RANK, interrupting osteoclast activation and bone resorption. This study examined the relationship between OPG and bone loss in women with CIOF. Methods Premenopausal women with stage I/II breast cancers receiving adjuvant chemotherapy were evaluated at chemotherapy initiation, 6 and 12 months. Bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN), follicle stimulating hormone (FSH), ionized calcium, osteocalcin, and OPG were serially measured. CIOF was defined as a negative pregnancy test, FSH levels >30 MIU/mL, and ≥3 months of amenorrhea. Results Forty women were enrolled; 31 (77.5%) met CIOF criteria. BMD significantly decreased (p < 0.001) in the CIOF group at both time points: LS BMD decreased from a median of 0.993 g/cm2 to 0.976 g/cm2 and 0.937 g/cm2 at 6 and 12 months, respectively. OPG was significantly elevated at 6 months (median increase 0.30 pmol/L, p = 0.015) and then decreased at 12 months to levels still above baseline (median difference 0.2 pmol/L, p = 0.70). Conclusions In what was likely a compensatory response to rapid bone loss, CIOF patients’ OPG levels increased at 6 months and then decreased at 12 months to values greater than baseline assessments. This phenomenon is described in other diseases, but never before in CIOF. PMID:25575458

  6. Identification of distinct fatigue trajectories in patients with breast cancer undergoing adjuvant chemotherapy

    PubMed Central

    Junghaenel, Doerte U.; Cohen, Jules; Schneider, Stefan; Neerukonda, Anu R.; Broderick, Joan E.

    2015-01-01

    Purpose The goal of this study was to characterize changes in daily fatigue in women undergoing chemotherapy for breast cancer. We examined whether there are subgroups of patients with distinct fatigue trajectories and explored potential psychosocial and biomedical predictors of these subgroups. Methods Participants were 77 women with breast cancer receiving adjuvant chemotherapy with AC-T (2-week cycle) and TC or TCH (3-week cycle) regimens. They completed 28 daily ratings online using an adapted version of the Patient-Reported Outcomes Measurement Information System (PROMIS®) fatigue instrument. Results Both regimens followed an “inverted-U shaped” fatigue pattern over approximately 2 weeks. Growth mixture modeling identified three patient subgroups with distinct trajectories. Fatigue scores in the “low fatigue” group (23%) increased following the infusion and quickly abated. The “transient fatigue” (27%) group had a very pronounced increase. Patients in the “high fatigue” (50%) group reported consistently elevated fatigue with a relatively small increase. Demographic and medical variables were not associated with fatigue trajectory. Patients in the “high fatigue” group reported significantly poorer physical, emotional, and social functioning, poorer general health, and more depressed mood than patients in the “low fatigue” group. The “transient fatigue” group reported significantly better physical and social functioning than the “high fatigue” group, but emotional distress and depression similar to the “high fatigue” group. Conclusions The identification of patient subgroups with distinct fatigue trajectories during chemotherapy is an essential step for developing preventative strategies and tailored interventions. Our results suggest that different trajectories are associated with patients’ psychosocial and general health. PMID:25876159

  7. Adjuvant therapy for highly malignant canine mammary tumours: Cox-2 inhibitor versus chemotherapy: a case-control prospective study.

    PubMed

    Arenas, C; Peña, L; Granados-Soler, J L; Pérez-Alenza, M D

    2016-07-30

    Cyclooxygenase-2 (Cox-2) enzyme participates in different steps of the carcinogenetic process and in canine mammary tumours (CMTs), a high expression of Cox-2 is associated with malignancy and tumour angiogenesis. The objectives of the study were to evaluate the disease-free survival (DFS) and overall survival (OS) of a Cox-2 inhibitor as adjuvant therapy in dogs with highly malignant (HM)-CMTs and compare it with that of dogs treated with chemotherapy and with control dogs. Twenty-eight dogs were prospectively included. After surgery, dogs were alternatively allocated into two treatment groups (chemotherapy with mitoxantrone n=8; Cox-2 inhibitor, firocoxib n=7). Control group (n=13) included dogs whose owners rejected adjuvant therapy. All dogs were followed up for two years or until death. The DFS was significantly higher in dogs that received adjuvant treatment (mitoxantrone or firocoxib) (P=0.030) than in control dogs. Dogs on firocoxib treatment had significantly higher DFS (P=0.015) and OS (P=0.048) than control dogs. The DFS and OS of dogs on mitoxantrone treatment were not statistically different from controls. In conclusion, this study supports the use of firocoxib for the treatment of HM-CMTs. Further studies are needed to compare the efficacy of chemotherapy drugs versus Cox-2 inhibitors as adjuvant treatment in these cases. PMID:27377395

  8. Biological characterization and selection criteria of adjuvant chemotherapy for early breast cancer: experience from the Italian observational NEMESI study

    PubMed Central

    2012-01-01

    Background International treatment guidelines recommend administration of adjuvant chemotherapy in early breast cancer based on clinical, prognostic and predictive parameters. Methods An observational study (NEMESI) was conducted in 63 Italian oncology centres in patients with early breast cancer. Age, performance status, concomitant disease, menopausal status, histology, tumor dimension (pT), axillary lymph node status (pN), grading (G), estrogen and progesterone receptor (ER and PgR), proliferative index (ki67 or MIB-1), human epidermal growth factor receptor 2 (HER2) and type of adjuvant treatment were recorded. The primary objective of the study was to define parameters influencing the decision to prescribe adjuvant chemotherapy and the type of chemotherapy. Results Data for 1894 patients were available. 69.0% postmenopausal, 67.0% pT1, 22.3% pTmic/pT1a/pT1b, 61.0% pN0, 48.7% luminal A, 18.1% luminal B, 16.1% HER2 positive, 8.7% triple negative, 8.4% unknown. 57.8% received adjuvant chemotherapy: 38.1% of luminal A, 67.3% luminal B, 88.2% HER2-positive, 97.6% triple negative. Regimens administered: 9.1% CMF-like, 48.8% anthracyclines, 38.4% anthracyclines plus taxanes, 3.7% taxanes alone. Increasing pT/pN and, marginally, HER2-positive were associated with the prescription of anthracyclines plus taxanes. Suboptimal schedules (CMF-like or AC/EC or FEC-75) were prescribed in 37.3% receiving chemotherapy, even in HER2-positive and triple negative disease (36.5% and 34.0%, respectively). Conclusions This study showed an overprescription of adjuvant chemotherapy for early breast cancer, particularly referred to luminal A. pT, pN and, marginally, HER2 were the principal determinants for the choice of chemotherapy type. Suboptimal chemotherapy regimens were adopted in at least one third of HER2-positve and triple negative. PMID:22672524

  9. Single Nucleotide Polymorphisms as Prognostic and Predictive Factors of Adjuvant Chemotherapy in Colorectal Cancer of Stages I and II

    PubMed Central

    Horvat, Matej; Potočnik, Uroš; Repnik, Katja; Kavalar, Rajko; Štabuc, Borut

    2016-01-01

    Colorectal cancer (CRC) is a highly heterogeneous disease regarding the stage at time of diagnosis and there is special attention regarding adjuvant chemotherapy in unselected patients with stage I and stage II. The clinicohistologically based TNM staging system with emphasis on histological evaluation of primary tumor and resected regional lymph nodes remains the standard of staging, but it has restricted sensitivity resulting in false downward stage migration. Molecular characteristics might predispose tumors to a worse prognosis and identification of those enables identifying patients with high risk of disease recurrence. Suitable predictive markers also enable choosing the most appropriate therapy. The current challenge facing adjuvant chemotherapy in stages I and II CRC is choosing patients with the highest risk of disease recurrence who are going to derive most benefit without facing unnecessary adverse effects. Single nucleotide polymorphisms (SNPs) are one of the potential molecular markers that might help us identify patients with unfavorable prognostic factors regarding disease initiation and recurrence and could determine selection of an appropriate chemotherapy regimen in the adjuvant and metastatic setting. In this paper, we discuss SNPs of genes involved in the multistep processes of cancerogenesis, metastasis, and the metabolism of chemotherapy that might prove clinically significant. PMID:26884752

  10. The role of adjuvant chemotherapy in nasopharyngeal carcinoma with bulky neck lymph nodes in the era of IMRT

    PubMed Central

    Xu, Tingting; Shen, Chunying; Ou, Xiaomin; He, Xiayun; Ying, Hongmei; Hu, Chaosu

    2016-01-01

    Nasopharyngeal carcinoma (NPC) patients with N2–3 diseases are prone to develop distant metastasis even treated with standard concurrent chemoradiotherapy (CCRT). Our study is aim to determine the optimal treatment strategy of these patients. Patients with histologically proven NPC were retrospectively analyzed according to the AJCC 2002 stage classification system. A total of 547 patients who had N2–3 diseases were enrolled. They were all treated with Intensity-modulated radiation therapy (IMRT) combined with systemic treatments, including radiotherapy alone (RT alone), neoadjuvant chemotherapy followed by radiotherapy (NACT+RT), CCRT, NACT+CCRT, NACT followed by radiotherapy and adjuvant chemotherapy (NACT+RT+AC), CCRT+AC and NACT+CCRT+AC. A subgroup analysis was also conducted. With a median follow-up time of 53.8 months, adjuvant chemotherapy significantly decreased the risk of distant metastasis (HR 0.413, 95% CI 0.194–0.881, p = 0.022) as well as significantly increased the OS (HR 0.398, 95% CI 0.187–0.848, p = 0.017) in patients with N3 disease. The addition of adjuvant chemotherapy seemed to provide benefits to patients with N3 stage NPC and the current study may indicate the need for further randomized investigation. PMID:26942700

  11. The role of adjuvant chemotherapy in nasopharyngeal carcinoma with bulky neck lymph nodes in the era of IMRT.

    PubMed

    Xu, Tingting; Shen, Chunying; Ou, Xiaomin; He, Xiayun; Ying, Hongmei; Hu, Chaosu

    2016-04-12

    Nasopharyngeal carcinoma (NPC) patients with N2-3 diseases are prone to develop distant metastasis even treated with standard concurrent chemoradiotherapy (CCRT). Our study is aim to determine the optimal treatment strategy of these patients. Patients with histologically proven NPC were retrospectively analyzed according to the AJCC 2002 stage classification system. A total of 547 patients who had N2-3 diseases were enrolled. They were all treated with Intensity-modulated radiation therapy (IMRT) combined with systemic treatments, including radiotherapy alone (RT alone), neoadjuvant chemotherapy followed by radiotherapy (NACT+RT), CCRT, NACT+CCRT, NACT followed by radiotherapy and adjuvant chemotherapy (NACT+RT+AC), CCRT+AC and NACT+CCRT+AC. A subgroup analysis was also conducted. With a median follow-up time of 53.8 months, adjuvant chemotherapy significantly decreased the risk of distant metastasis (HR 0.413, 95% CI 0.194-0.881, p = 0.022) as well as significantly increased the OS (HR 0.398, 95% CI 0.187-0.848, p = 0.017) in patients with N3 disease. The addition of adjuvant chemotherapy seemed to provide benefits to patients with N3 stage NPC and the current study may indicate the need for further randomized investigation. PMID:26942700

  12. Cost-effectiveness of adjuvant FOLFOX and 5FU/LV chemotherapy for patients with stage II colon cancer

    PubMed Central

    Ayvaci, Mehmet U.S.; Shi, Jinghua; Alagoz, Oguzhan; Lubner, Sam

    2014-01-01

    Purpose We evaluated the cost-effectiveness of adjuvant chemotherapy using 5-fluorouracil, leucovorin (5FU/LV), and oxaliplatin (FOLFOX) compared with 5FU/LV alone and 5FU/LV compared with observation alone for patients who had resected stage II colon cancer. Methods We developed two Markov models to represent the adjuvant chemotherapy and follow-up periods and a single Markov model to represent the observation group. We used calibration to estimate the transition probabilities among different toxicity levels. The base-case considered 60-year-old patients who had undergone an uncomplicated hemicolectomy for stage II colon cancer and was medically fit to receive 6 months of adjuvant chemotherapy. We measured health outcomes in quality-adjusted life-years (QALYs) and estimated costs using 2007 US$. Results In the base-case, adjuvant chemotherapy of FOLFOX regimen had an incremental cost-effectiveness ratio (ICER) of $54,359/QALY compared with the 5FU/LV regimen and the 5FU/LV regimen had an ICER of $14,584/QALY compared with the observation group from the third-party payer perspective. The ICER values were most sensitive to 5-year relapse probability, cost of adjuvant chemotherapy, and the discount rate for the FOLFOX arm, whereas the ICER value of 5FU/LV was most sensitive to the 5-year relapse probability, 5-year survival probability, and the relapse cost. The probabilistic sensitivity analysis indicate that the ICER of 5FU/LV is less than $50,000/QALY with a probability of 99.62% and the ICER of FOLFOX as compared to 5FU/LV is less than $50,000/QALY and $100,000/QALY with a probability of 44.48% and 97.24%, respectively. Conclusion While adjuvant chemotherapy with 5FU/LV is cost-effective at all ages for patients who had undergone an uncomplicated hemicolectomy for stage II colon cancer, FOLFOX is not likely to be cost-effective as compared to 5FU/LV. PMID:23313932

  13. Salivary Gland Tumors Treated With Adjuvant Intensity-Modulated Radiotherapy With or Without Concurrent Chemotherapy

    SciTech Connect

    Schoenfeld, Jonathan D.; Sher, David J.; Norris, Charles M.; Haddad, Robert I.; Posner, Marshall R.; Balboni, Tracy A.; Tishler, Roy B.

    2012-01-01

    Purpose: To analyze the recent single-institution experience of patients with salivary gland tumors who had undergone adjuvant intensity-modulated radiotherapy (IMRT), with or without concurrent chemotherapy. Patients and Methods: We performed a retrospective analysis of 35 salivary gland carcinoma patients treated primarily at the Dana-Farber Cancer Institute between 2005 and 2010 with surgery and adjuvant IMRT. The primary endpoints were local control, progression-free survival, and overall survival. The secondary endpoints were acute and chronic toxicity. The median follow-up was 2.3 years (interquartile range, 1.2-2.8) among the surviving patients. Results: The histologic types included adenoid cystic carcinoma in 15 (43%), mucoepidermoid carcinoma in 6 (17%), adenocarcinoma in 3 (9%), acinic cell carcinoma in 3 (9%), and other in 8 (23%). The primary sites were the parotid gland in 17 (49%), submandibular glands in 6 (17%), tongue in 4 (11%), palate in 4 (11%), and other in 4 (11%). The median radiation dose was 66 Gy, and 22 patients (63%) received CRT. The most common chemotherapy regimen was carboplatin and paclitaxel (n = 14, 64%). A trend was seen for patients undergoing CRT to have more adverse prognostic factors, including Stage T3-T4 disease (CRT, n = 12, 55% vs. n = 4, 31%, p = .29), nodal positivity (CRT, n = 8, 36% vs. n = 1, 8%, p = .10), and positive margins (n = 13, 59% vs. n = 5, 38%, p = .30). One patient who had undergone CRT developed an in-field recurrence, resulting in an overall actuarial 3-year local control rate of 92%. Five patients (14%) developed distant metastases (1 who had undergone IMRT only and 4 who had undergone CRT). Acute Grade 3 mucositis, esophagitis, and dermatitis occurred in 8%, 8%, and 8% (1 each) of IMRT patients and in 18%, 5%, and 14% (4, 1, and 3 patients) of the CRT group, respectively. No acute Grade 4 toxicity occurred. The most common late toxicity was Grade 1 xerostomia (n = 8, 23%). Conclusions: Treatment of

  14. Phase 2 Study of Erlotinib Combined With Adjuvant Chemoradiation and Chemotherapy in Patients With Resectable Pancreatic Cancer

    SciTech Connect

    Herman, Joseph M.; Fan, Katherine Y.; Wild, Aaron T.; Hacker-Prietz, Amy; Wood, Laura D.; Blackford, Amanda L.; Ellsworth, Susannah; Zheng, Lei; Le, Dung T.; De Jesus-Acosta, Ana; Hidalgo, Manuel; Donehower, Ross C.; Schulick, Richard D.; Edil, Barish H.; Choti, Michael A.; Hruban, Ralph H.; and others

    2013-07-15

    Purpose: Long-term survival rates for patients with resected pancreatic ductal adenocarcinoma (PDAC) have stagnated at 20% for more than a decade, demonstrating the need to develop novel adjuvant therapies. Gemcitabine-erlotinib therapy has demonstrated a survival benefit for patients with metastatic PDAC. Here we report the first phase 2 study of erlotinib in combination with adjuvant chemoradiation and chemotherapy for resected PDAC. Methods and Materials: Forty-eight patients with resected PDAC received adjuvant erlotinib (100 mg daily) and capecitabine (800 mg/m{sup 2} twice daily Monday-Friday) concurrently with intensity modulated radiation therapy (IMRT), 50.4 Gy over 28 fractions followed by 4 cycles of gemcitabine (1000 mg/m{sup 2} on days 1, 8, and 15 every 28 days) and erlotinib (100 mg daily). The primary endpoint was recurrence-free survival (RFS). Results: The median follow-up time was 18.2 months (interquartile range, 13.8-27.1). Lymph nodes were positive in 85% of patients, and margins were positive in 17%. The median RFS was 15.6 months (95% confidence interval [CI], 13.4-17.9), and the median overall survival (OS) was 24.4 months (95% CI, 18.9-29.7). Multivariate analysis with adjustment for known prognostic factors showed that tumor diameter >3 cm was predictive for inferior RFS (hazard ratio, 4.01; P=.001) and OS (HR, 4.98; P=.02), and the development of dermatitis was associated with improved RFS (HR, 0.27; P=.009). During CRT and post-CRT chemotherapy, the rates of grade 3/4 toxicity were 31%/2% and 35%/8%, respectively. Conclusion: Erlotinib can be safely administered with adjuvant IMRT-based CRT and chemotherapy. The efficacy of this regimen appears comparable to that of existing adjuvant regimens. Radiation Therapy Oncology Group 0848 will ultimately determine whether erlotinib produces a survival benefit in patients with resected pancreatic cancer.

  15. Role of Adjuvant Chemotherapy in ypT0-2N0 Patients Treated with Preoperative Chemoradiation Therapy and Radical Resection for Rectal Cancer

    SciTech Connect

    Park, In Ja; Kim, Dae Yong; Kim, Hee Cheol; Kim, Nam Kyu; Kim, Hyeong-Rok; Kang, Sung-Bum; Choi, Gyu-Seog; Lee, Kang Young; Kim, Seon-Hahn; Oh, Seung Taek; Lim, Seok-Byung; Kim, Jin Cheon; Oh, Jae Hwan; Kim, Sun Young; Lee, Woo Yong; Lee, Jung Bok; Yu, Chang Sik

    2015-07-01

    Objective: To explore the role of adjuvant chemotherapy for patients with ypT0-2N0 rectal cancer treated by preoperative chemoradiation therapy (PCRT) and radical resection. Patients and Methods: A national consortium of 10 institutions was formed, and patients with ypT0-2N0 mid- and low-rectal cancer after PCRT and radical resection from 2004 to 2009 were included. Patients were categorized into 2 groups according to receipt of additional adjuvant chemotherapy: Adj CTx (+) versus Adj CTx (−). Propensity scores were calculated and used to perform matched and adjusted analyses comparing relapse-free survival (RFS) between treatment groups while controlling for potential confounding. Results: A total of 1016 patients, who met the selection criteria, were evaluated. Of these, 106 (10.4%) did not receive adjuvant chemotherapy. There was no overall improvement in 5-year RFS as a result of adjuvant chemotherapy [91.6% for Adj CTx (+) vs 87.5% for Adj CTx (−), P=.18]. There were no differences in 5-year local recurrence and distant metastasis rate between the 2 groups. In patients who show moderate, minimal, or no regression in tumor regression grade, however, possible association of adjuvant chemotherapy with RFS would be considered (hazard ratio 0.35; 95% confidence interval 0.14-0.88; P=.03). Cox regression analysis after propensity score matching failed to show that addition of adjuvant chemotherapy was associated with improved RFS (hazard ratio 0.81; 95% confidence interval 0.39-1.70; P=.58). Conclusions: Adjuvant chemotherapy seemed to not influence the RFS of patients with ypT0-2N0 rectal cancer after PCRT followed by radical resection. Thus, the addition of adjuvant chemotherapy needs to be weighed against its oncologic benefits.

  16. Predominant histologic subtype in lung adenocarcinoma predicts benefit from adjuvant chemotherapy in completely resected patients: discovery of a holy grail?

    PubMed

    Russell, Prudence Anne; Wright, Gavin Michael

    2016-01-01

    The recently published 2015 World Health Organisation (WHO) classification of lung tumors, which is based on the 2011 International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ATS) multidisciplinary classification, recommends diagnosis of resected lung adenocarcinoma according to the predominant histologic subtype. This has been shown to correlate with overall and disease-free survival (DFS) in many studies from four continents. Now classification according to predominant histologic subtype has been demonstrated to predict benefit from adjuvant chemotherapy in a subset of patients with completely resected lung adenocarcinoma previously included in the International Adjuvant Lung Cancer Trial (IALT), JBR.10, Cancer and Leukemia Group B (CALGB) 9633 and Adjuvant Navelbine International Trialist Association 01 (ANITA) adjuvant chemotherapy trials, all of which were part of the LACE-Bio study. This "hot-off-the press" landmark investigation further cements the clinical importance of classification of resected lung adenocarcinoma according to predominant histologic subtype and suggests that it could be a critical factor for patient stratification in future clinical trials. PMID:26855952

  17. Predominant histologic subtype in lung adenocarcinoma predicts benefit from adjuvant chemotherapy in completely resected patients: discovery of a holy grail?

    PubMed Central

    Wright, Gavin Michael

    2016-01-01

    The recently published 2015 World Health Organisation (WHO) classification of lung tumors, which is based on the 2011 International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ATS) multidisciplinary classification, recommends diagnosis of resected lung adenocarcinoma according to the predominant histologic subtype. This has been shown to correlate with overall and disease-free survival (DFS) in many studies from four continents. Now classification according to predominant histologic subtype has been demonstrated to predict benefit from adjuvant chemotherapy in a subset of patients with completely resected lung adenocarcinoma previously included in the International Adjuvant Lung Cancer Trial (IALT), JBR.10, Cancer and Leukemia Group B (CALGB) 9633 and Adjuvant Navelbine International Trialist Association 01 (ANITA) adjuvant chemotherapy trials, all of which were part of the LACE-Bio study. This “hot-off-the press” landmark investigation further cements the clinical importance of classification of resected lung adenocarcinoma according to predominant histologic subtype and suggests that it could be a critical factor for patient stratification in future clinical trials. PMID:26855952

  18. Primary proximal epithelioid sarcoma of the lung successfully treated with pneumonectomy and adjuvant chemotherapy.

    PubMed

    Saha, Debjit; Basu, Arnab; Maiti, Abhishek; Rodriguez, Estelamari

    2016-01-01

    Primary sarcomas of the lung and proximal epithelial sarcomas (PESs) are extremely rare. Inactivation of INI1 has been found in the majority of epithelioid sarcoma (ES). We report the third known case of a primary PES of the lung along with immunohistochemical data. A 41-year-old man with HIV infection, on highly active antiretroviral therapy, presented with haemoptysis, shortness of breath and progressive weight loss for 2 months. He was eventually diagnosed with stage IIA cT2bN0M0 grade-2 primary PES of the lung. This patient underwent pneumonectomy and adjuvant chemotherapy with ifosfamide and doxorubicin. He remains in remission 36 months since diagnosis. Our case stands to help other clinicians as treatment of such rare cases is often reliant on case reports. We also posit a possible pathogenic mechanism given a history of HIV infection in this patient. The association of INI1 mutation with other atypical sarcomas in patients with HIV infection merits further evaluation. PMID:27045049

  19. BMI Influences Prognosis Following Surgery and Adjuvant Chemotherapy for Lymph Node Positive Breast Cancer

    PubMed Central

    Vitolins, Mara Z.; Kimmick, Gretchen G.; Case, L. Douglas

    2016-01-01

    Increased body mass index (BMI) at diagnosis has been shown to be associated with an increased risk of disease recurrence and death. However, the association has not been consistent in the literature and may depend on several factors such as menopausal status, extent of disease, and receptor status. We performed a secondary analysis on what we believe is the largest prospective trial of adjuvant chemotherapy to assess the effect of BMI on prognosis in women with lymph node positive breast cancer. The study included 636 women with a median follow-up of over 13 years. Cox’s proportional hazards regression model was used to assess the effect of BMI on outcomes. Kaplan–Meier methods were used to estimate survival curves and log rank tests were used to assess differences in survival for BMI groups. We found that increased BMI was generally predictive of faster time to recurrence and decreased survival, but that the relationship was stronger for younger women, those with progesterone receptor negative disease and those with a greater number of lymph nodes that were positive. PMID:18540954

  20. [Adjuvant chemotherapy for breast cancer and fertility: estimation of the impact, options of preservation and role of the oncologist].

    PubMed

    Mailliez, Audrey; Decanter, Christine; Bonneterre, Jacques

    2011-07-01

    Fifty-two thousand new breast cancers occur each year in France, 7% in patients less than 40 years. The standard regimens of adjuvant chemotherapy for breast cancer now include anthracyclines and taxanes. These therapeutics advances have significantly improved the prognosis of these young women who may later wish to become mother and have biological offspring. The impact of chemotherapy on reproductive function should be accurately assessed and the ovarian reserve has to be taken into account. The estimated risk of chemo-induced amenorrhea and infertility has to be balanced with the expected results and risks of methods of fertility preservation. The place of different options for fertility preservation depends on patient age, presence or not of a partner and the time available before the initiation of treatment. For these breast cancer patients who will receive chemotherapy, new techniques of in vitro oocyte maturation seem promising. Even if some ethical and technical issues are unresolved, fertility preservation must now be part of the management of these young patients receiving adjuvant chemotherapy for breast cancer. This new approach must be multidisciplinary and complex. PMID:21700552

  1. Adjuvant chemotherapy for soft-tissue sarcoma: review and meta-analysis of the published results of randomised clinical trials.

    PubMed Central

    Tierney, J. F.; Mosseri, V.; Stewart, L. A.; Souhami, R. L.; Parmar, M. K.

    1995-01-01

    Fifteen published randomised trials comparing adjuvant chemotherapy with no chemotherapy in soft-tissue sarcoma (STS) were identified (1546 patients). A qualitative review and a meta-analysis of this published literature were performed. With the qualitative review it was not possible to synthesise the apparently conflicting results of individual trials. The meta-analysis of the published data suggests an improvement in survival at 2 years (OR = 0.73, 95% CI = 0.53-0.99, P = 0.044) and at 5 years (OR = 0.59, 95% CI = 0.45-0.78, P = 0.0002) in favour of chemotherapy. However, the assumptions and approximations required to conduct this quantitative summary demand that the results are interpreted with caution. The only reliable means of assessing the current evidence on whether adjuvant chemotherapy has a role in the treatment of patients with STS, is to collect, check and reanalyse individual patients data (IPD) from each trial centrally, and formally combine the results in a stratified time-to-event analysis. Such an IPD analysis is currently being undertaken by an international collaborative group. PMID:7640234

  2. Adjuvant chemotherapy of pT1a and pT1b breast carcinoma: results from the NEMESI study

    PubMed Central

    2012-01-01

    Background The prognosis of pT1a-pT1b breast cancer (BC) used to be considered very good, with a 10-y RFS of 90%. However, some retrospective studies reported a 10-y RFS of 81%–86% and suggested benefit from adjuvant systemic therapy. Methods To evaluate the variables that determined the choice of adjuvant chemotherapy and the type of chemotherapy delivered in pT1a-pT1b BC, we analysed the small tumours enrolled in the NEMESI study. Results Out of 1,894 patients with pathological stage I-II BC enrolled in NEMESI, 402 (21.2%) were pT1a-pT1b. Adjuvant chemotherapy was delivered in 127/402 (31.59%). Younger age, grading G3, high proliferative index, ER-negative and HER2-positive status were significantly associated with the decision to administer adjuvant chemotherapy. An anthracycline without taxane regimen was administered in 59.1% of patients, anthracycline with taxane in 24.4%, a CMF-like regimen in 14.2% and taxane in 2.4%. Adjuvant chemotherapy was administered in 88.4% triple-negative and 73.46% HER2-positive pT1a-pT1b BC. Adjuvant trastuzumab was delivered in 30/49 HER2-positive BC (61.2%). Conclusions Adjuvant chemotherapy was delivered in 31.59% T1a-pT1b BC treated at 63 Italian oncological centres from January 2008 to June 2008. The choice to deliver chemotherapy was based on biological prognostic factors. Anthracycline-based chemotherapy was administered in 83.5% patients. PMID:22545982

  3. 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.

  4. Adjuvant chemotherapy in rectal cancer: defining subgroups who may benefit after neoadjuvant chemoradiation and resection

    PubMed Central

    Maas, Monique; Nelemans, Patty J; Valentini, Vincenzo; Crane, Christopher H; Capirci, Carlo; Rödel, Claus; Nash, Garrett M; Kuo, Li-Jen; Glynne-Jones, Rob; García-Aguilar, Julio; Suárez, Javier; Calvo, Felipe A; Pucciarelli, Salvatore; Biondo, Sebastiano; Theodoropoulos, George; Lambregts, Doenja MJ; Beets-Tan, Regina GH; Beets, Geerard L

    2016-01-01

    Recent literature suggests that the benefit of adjuvant chemotherapy (aCT) for rectal cancer patients might depend on the response to neoadjuvant chemoradiation (CRT). Aim was to evaluate whether the effect of aCT in rectal cancer is modified by response to CRT and to identify which patients benefit from aCT after CRT, by means of a pooled analysis of individual patient data from 13 datasets. Patients were categorised into 3 groups: pCR (ypT0N0), ypT1-2 tumour and ypT3-4 tumour. Hazard ratios for the effect of aCT were derived from multivariable Cox regression analyses. Primary outcome measure was recurrence-free survival (RFS). 1723(52%) of 3313 included patients received aCT. 898 patients had a pCR, 966 had a ypT1-2 tumour and 1302 had a ypT3-4 tumour. For 122 patients response category was missing and 25 patients had ypT0N+. Median follow-up for all patients was 51 (0-219) months. Hazard ratios for RFS with 95%CI for patients treated with aCT were 1.25(0.68-2.29), 0.58(0.37-0.89) and 0.83(0.66-1.10) for patients with pCR, ypT1-2 and ypT3-4 tumours, respectively. The effect of aCT in rectal cancer patients treated with CRT differs between subgroups. Patients with a pCR after CRT may not benefit from aCT, whereas patients with residual tumour had superior outcomes when aCT was administered. The test for interaction did not reach statistical significance, but the results support further investigation of a more individualized approach to administer aCT after CRT and surgery based on pathologic staging. PMID:25418551

  5. The effects of postoperative adjuvant chemotherapy and radiotherapy on testicular function in men undergoing treatment for soft tissue sarcoma

    SciTech Connect

    Shamberger, R.C.; Sherins, R.J.; Rosenberg, S.A.

    1981-05-15

    Testicular function was studied in 26 men with sarcoma who received adjuvant treatment with doxorubicin, cyclophosphamide, and high-dose methotrexate (with or without radiotherapy). Testicular size, sperm output, and serum FSH, LH and testosterone levels were assessed after treatment. Five of 17 men who received chemotherapy or chemotherapy with radiotherapy to the neck, arm, chest, or leg, had normal testicular function. Eight of the remaining 12 men who provided ejaculates were oligospermic or azoospermic and serum FSH was increased threefold and LH twofold; testosterone levels were normal. In the five men with normal testicular function, FSH was increased fourfold during therapy but returned to normal six to 21 months after treatment. In men less than 40 years old, the mean FSH was less than that of men over 40 years of age (P . to 0.05), suggesting that recovery from the injury was age-related. By contrast, all nine men who received chemotherapy plus radiotherapy to the abdomen or thigh had decreased testicular size, azoospermia, fourfold increase in FSH, and twofold increase in LH levels; but testosterone concentration was normal. These data increase in FSH, and reversible testicular injury occurs after treatment with doxorubicin, cyclophosphamide, and high-dose methotrexate; recovery is age-related. However, these agents in combination with use of adjuvant radiotherapy to the thigh or abdomen may produce permanent testicular injury even in young patients.

  6. Effects of postoperative adjuvant chemotherapy and radiotherapy on testicular function in men undergoing treatment for soft tissue sarcoma

    SciTech Connect

    Shamberger, R.C.; Sherins, R.J.; Rosenberg, S.A.

    1981-05-15

    Testicular function was studied in 26 men with sarcoma who received adjuvant treatment with doxorubicin, cyclophosphamide, and high-dose methotrexate (with or without radiotherapy). Testicular size, sperm output, and serum FSH, LH and testosterone levels were assessed after treatment. Five of 17 men who received chemotherapy or chemotherapy with radiotherapy to the neck, arm, chest or leg, had normal testicular function. Eight of the remaining 12 men who provided ejaculates were oligospermic or azoospermic and serum FSH was increased threefold and LH twofold; testosterone levels were normal. In men less than 40 years old, the mean FSH level was less than that of men over 40 years of age (P = 0.05), suggesting that recovery from the injury was age-related. By contrast, all nine men who received chemotherapy plus radiotherapy to the abdomen or thigh had decreased testicular size, azoospermia, fourfold increase in FSH, and twofold increase in LH levels; but testosterone concentration was normal. These data indicate that reversible testicular injury occurs after treatment with doxorubicin, cyclophosphamide, and high-dose methotrexate; recovery is age-related. However, these agents in combination with use of adjuvant radiotherapy to the thigh or abdomen may produce permanent testicular injury even in young patients.

  7. Prospective cohort study of febrile neutropenia in breast cancer patients with neoadjuvant and adjuvant chemotherapy: CSPOR-BC FN study.

    PubMed

    Ishikawa, Takashi; Sakamaki, Kentaro; Narui, Kazutaka; Kaise, Hiroshi; Tsugawa, Koichiro; Ichikawa, Yasushi; Mukai, Hirofumi

    2016-07-01

    With the increasing use of adjuvant chemotherapy for treating early breast cancer, febrile neutropenia management has become crucial. Guidelines for febrile neutropenia management are mostly based on a Caucasian population survey although ethnic differences are reported in terms of adverse events. We survey the current status of febrile neutropenia and risk factors in Japanese female breast cancer patients receiving neoadjuvant and adjuvant chemotherapy regimens potential for febrile neutropenia. Subsequently, we plan to conduct a multicenter prospective cohort study involving 1000 patients with operable breast cancer. With the current state of oral antibiotics being routinely prescribed without hematology tests, we survey febrile neutropenia based on two different definitions, namely, true febrile neutropenia: ≥37.5°C and Grade 4 neutropenia, and surrogate febrile neutropenia: ≥37.5°C and oral antibiotic and antipyretic intake. The comparison of true febrile neutropenia and surrogate febrile neutropenia incidences is anticipated to provide information on the safety and feasibility of chemotherapy management without performing blood tests. PMID:27162322

  8. Concurrent Radiotherapy and Gemcitabine for Unresectable Pancreatic Adenocarcinoma: Impact of Adjuvant Chemotherapy on Survival

    SciTech Connect

    Ogawa, Kazuhiko; Ito, Yoshinori; Hirokawa, Naoki; Shibuya, Keiko; Kokubo, Masaki; Ogo, Etsuyo; Shibuya, Hitoshi; Saito, Tsutomu; Onishi, Hiroshi; Karasawa, Katsuyuki; Nemoto, Kenji; Nishimura, Yasumasa

    2012-06-01

    Purpose: To retrospectively analyze results of concurrent chemoradiotherapy (CCRT) using gemcitabine (GEM) for unresectable pancreatic adenocarcinoma. Methods and Materials: Records of 108 patients treated with concurrent external beam radiotherapy (EBRT) and GEM were reviewed. The median dose of EBRT in all 108 patients was 50.4 Gy (range, 3.6-60.8 Gy), usually administered in conventional fractionations (1.8-2 Gy/day). During radiotherapy, most patients received GEM at a dosage of 250 to 350 mg/m{sup 2} intravenously weekly for approximately 6 weeks. After CCRT, 59 patients (54.6%) were treated with adjuvant chemotherapy (AC), mainly with GEM. The median follow-up for all 108 patients was 11.0 months (range, 0.4-37.9 months). Results: Initial responses after CCRT for 85 patients were partial response: 26 patients, no change: 51 patients and progressive disease: 8 patients. Local progression was observed in 35 patients (32.4%), and the 2-year local control (LC) rate in all patients was 41.9%. Patients treated with total doses of 50 Gy or more had significantly more favorable LC rates (2-year LC rate, 42.9%) than patients treated with total doses of less than 50 Gy (2-year LC rate, 29.6%). Regional lymph node recurrence was found in only 1 patient, and none of the 57 patients with clinical N0 disease had regional lymph node recurrence. The 2-year overall survival (OS) rate and the median survival time in all patients were 23.5% and 11.6 months, respectively. Patients treated with AC had significantly more favorable OS rates (2-year OS, 31.8%) than those treated without AC (2-year OS, 12.4%; p < 0.0001). On multivariate analysis, AC use and clinical T stage were significant prognostic factors for OS. Conclusions: CCRT using GEM yields a relatively favorable LC rate for unresectable pancreatic adenocarcinoma, and CCRT with AC conferred a survival benefit compared to CCRT without AC.

  9. Effect of Active Hexose-Correlated Compound in Women Receiving Adjuvant Chemotherapy for Breast Cancer: A Retrospective Study

    PubMed Central

    Hangai, Sho; Iwase, Satoru; Kawaguchi, Takashi; Kogure, Yasunori; Matsunaga, Tadaharu; Nagumo, Yoshinori; Yamaguchi, Takuhiro

    2013-01-01

    Abstract Objectives Anthracyclines and taxanes are often used as first-line chemotherapy treatments in patients with breast cancer. There are, however, significant toxicity and side effects associated with these therapies. Previous studies have demonstrated that active hexose-correlated compound (AHCC) reduces such side effects. The present study explored the beneficial effects of AHCC on adverse events in patients receiving adjuvant chemotherapy for breast cancer. Subjects Forty-one women who were treated with anthracyclines and taxanes at Nagumo Clinic in Tokyo from October 2004 to March 2011 were selected for this study. Outcome measures We compared the occurrence of adverse events in patients who received AHCC with those who did not receive AHCC. Using Fisher's exact tests, we also compared the worst-grade adverse events in each treatment cycle. Generalized estimating equations were employed to compare longitudinal changes, and the use of granulocyte colony-stimulating factor, in the two groups was analyzed using Student's t-test. Results We found that, compared to the control group, the AHCC group had significantly fewer neutrophil-related events (odds ratio, 0.30; p=0.016), significantly lower use of granulocyte colony-stimulating factor, and a higher (although not significant) rate of adverse events associated with γ-glutamyl transpeptidase. Conclusions AHCC has the potential to reduce the severity of neutropenia induced by breast cancer chemotherapy and the use of G-CSF during chemotherapy. PMID:23829813

  10. A case of long-term 24-month survival in pancreatic anaplastic carcinoma (giant cell type) after S1 postoperative adjuvant chemotherapy

    PubMed Central

    Nitta, Toshikatsu; Fujii, Kensuke; Kataoka, Jun; Tominaga, Tomo; Kawasaki, Hiroshi; Ishibashi, Takashi

    2016-01-01

    We herein describe the case of a 70-year-old female patient diagnosed with pancreatic carcinoma. An abdominal enhanced computed tomography scan revealed a poorly enhanced mass (17 mm × 15 mm in size) in the pancreatic head. Magnetic resonance cholangiopancreatography revealed stenosis of the main pancreatic and common bile ducts caused by a mass-neighboring cyst. Based on these findings, we performed subtotal stomach-preserving pancreaticoduodenectomy. The patient demonstrated a good postoperative course, and was discharged from our hospital in remission 49 days after the surgery. Pathological findings confirmed that it was anaplastic pancreas carcinoma (giant cell type). After the surgery, we performed S-1 adjuvant chemotherapy 100 mg/day for four weeks, repeated similarly every six weeks for a total of four courses. We have followed this case for over 2 years so far with adjuvant chemotherapy, and no recurrence or metastasis has been revealed. Adjuvant chemotherapy with S-1 in patients with resected anaplastic carcinoma of the pancreas is also recommended as a result of Japan Adjuvant Study Group of Pancreatic Cancer 01(JASPAC-01) like the ordinary pancreatic ductal carcinomas. There is a possibility to achieve long-term survival in cases in which multidisciplinary treatment such as a curative resection and adjuvant chemotherapy are performed. PMID:27111877

  11. Short-term mortality in older patients treated with adjuvant chemotherapy for early-stage breast cancer.

    PubMed

    Rosenstock, Aron S; Lei, Xiudong; Tripathy, Debu; Hortobagyi, Gabriel N; Giordano, Sharon H; Chavez-MacGregor, Mariana

    2016-06-01

    Chemotherapy for early-stage breast cancer has lowered cancer recurrence and deaths. However, short-term mortality rates due to cancer or treatment in the general population remain largely unknown. In this study, we evaluate the short-term mortality rate and the determinants of such outcome among a cohort of older breast cancer patients treated with adjuvant chemotherapy. This is a population-based study based on the Surveillance, Epidemiology, and End Results Program (SEER)-Medicare and the Texas Cancer Registry (TCR)-Medicare databases. Patients diagnosed with early-stage breast cancer between 2003 and 2011 who were 66 years or older and were treated with adjuvant chemotherapy within 6 months of diagnosis were included. Short-term mortality was defined as death from any cause within one year of breast cancer diagnosis. Descriptive statistics and multivariable logistic regression modeling were used for the analysis. Of the 21,536 patients included, a total of 625 (2.9 %) died within one year of breast cancer diagnosis. In multivariate analysis, older age (using 66-70 as reference category; 71-75 years OR 1.31, 95 % CI 1.05-1.62; 76-80 years OR 1.73, 95 % CI 1.36-2.19; >80 years OR 3.48, 95 % CI 2.7-4.48) and higher comorbidity index (using Charlson score of 0 as a reference, those with score of 1 or >2 had higher risk OR 1.46, 95 % CI 1.19-1.8 and OR 2.98, 95 % CI 2.42-3.67, respectively) were associated with the increased risk of short-term mortality. Other factors significantly associated with the outcome were higher grade and stage, ER-negative status, poor census tract area, and mastectomy. The findings of this study revealed that, in this large cohort of older breast cancer patients treated with adjuvant chemotherapy, 2.9 % of the population died within one year of breast cancer diagnosis. Finally, it was concluded that tumor- and patient-related characteristics were associated with short-term death. Our findings add relevant information that can be

  12. Irinotecan and capecitabine combination chemotherapy in a patient with triple-negative breast cancer relapsed after adjuvant chemotherapy with anthracycline and taxane.

    PubMed

    Lee, Anna; Go, Se-Il; Lee, Won Sup; Lee, Un Seok; Kim, Moon Jin; Kang, Myoung Hee; Lee, Gyeong-Won; Kim, Hoon-Gu; Kang, Jung Hun; Jeon, Kyung-Nyeo; Cho, Jae Min; Lee, Jeong-Hee

    2015-01-01

    The most effective regimen for taxane- and anthracycline-refractory triple-negative breast cancer (TNBC) has not yet been established. Capecitabine was approved by the US Food and Drug Administration for the treatment of advanced breast cancer and has shown efficacy in advanced breast cancer refractory to anthracyclines and taxanes. Irinotecan has synergism with 5-fluorouracil and shows efficacy in advanced breast cancer. Here we report on a patient with TNBC who relapsed with widespread bone and lung metastases shortly after adjuvant anthracycline followed by taxane chemotherapy. She achieved a metabolic complete response with irinotecan and capecitabine combination therapy and had 10 months' progression-free survival and 22 months' overall survival. She relapsed with and died of brain metastasis without any definite signs of progression of the lung and bone lesions she had had before the irinotecan and capecitabine combination therapy. To validate this favorable result, larger clinical trials are warranted in patients with metastatic or relapsed TNBC. PMID:25702650

  13. Combination adjuvant chemotherapy with oxaliplatin, 5-fluorouracil and leucovorin after liver transplantation for hepatocellular carcinoma: a preliminary open-label study.

    PubMed

    Zhang, Qing; Chen, Hong; Li, Qin; Zang, Yunjin; Chen, Xinguo; Zou, Weilong; Wang, Letian; Shen, Zhong-Yang

    2011-12-01

    The purpose of this study was to evaluate the efficacy of postoperative adjuvant chemotherapy with FOLFOX regimen on the outcome after LT for HCC patients who did not meet the Milan criteria. Ninety-five consecutive HCC patients with liver cirrhosis undergoing LT were enrolled. Fifty-eight who did not meet the Milan criteria were randomized to open-label treatment with or without adjuvant chemotherapy after LT (n = 29/group). The FOLFOX chemotherapy protocol comprised 3-week cycles of oxaliplatin 100 mg/m(2) on day 1, leucovorin (calcium folinate, CF) 200 mg/m(2) on day 1 followed by 3-day, and 5-fluorouracil (5-FU) 2000 mg/m(2) as a 48-h continuous infusion, for up to six courses in the 1st year after transplantation. Median survival was extended by 4.57 months by combination chemotherapy. The 1- and 3-year survival rates were 89.7% and 79.3% with chemotherapy versus 69.0% and 62.1% without chemotherapy. The cumulative 1-year survival was significantly increased by chemotherapy (log-rank test, P = 0.043). The 6-month tumor-free survival rate was 24.1% higher with chemotherapy than without. The recurrence rate after LT was significantly different between the two groups at 6 months (P = 0.036), but not at 3 years (P = 0.102). The chemotherapy regimen was generally well tolerated. Post-LT adjuvant chemotherapy with oxaliplatin/5-FU/CF could not prevent tumor recurrence post-LT but may contribute to improve the survival of HCC patients who do not meet the Milan criteria. These results should be verified in a larger sample with a longer follow-up period. PMID:21809025

  14. Efficacy of platinum chemotherapy agents in the adjuvant setting for adenosquamous carcinoma of the pancreas

    PubMed Central

    Wild, Aaron T.; Dholakia, Avani S.; Fan, Katherine Y.; Kumar, Rachit; Moningi, Shalini; Rosati, Lauren M.; Laheru, Daniel A.; Zheng, Lei; De Jesus-Acosta, Ana; Ellsworth, Susannah G.; Hacker-Prietz, Amy; Voong, Khinh R.; Tran, Phuoc T.; Hruban, Ralph H.; Pawlik, Timothy M.; Wolfgang, Christopher L.

    2015-01-01

    Background Pancreatic adenosquamous carcinoma (PASC) accounts for only 1-4% of all exocrine pancreatic cancers and carries a particularly poor prognosis. This retrospective study was performed to determine whether inclusion of a platinum agent as part of adjuvant therapy is associated with improved survival in patients with resected PASC. Methods Records of all patients who underwent pancreatic resection at Johns Hopkins Hospital from 1986 to 2012 were reviewed to identify those with PASC. Multivariable Cox proportional hazards modeling was used to assess for significant associations between patient characteristics and survival. Results In total, 62 patients (1.1%) with resected PASC were identified among 5,627 cases. Median age was 68 [interquartile range (IQR), 57-77] and 44% were female. Multivariate analysis revealed that, among all patients (n=62), the following factors were independently predictive of poor survival: lack of adjuvant therapy [hazard ratio (HR) =3.6; 95% confidence interval (CI), 1.8-7.0; P<0.001], margin-positive resection (HR =3.5; 95% CI, 1.8-6.8; P<0.001), lymph node involvement (HR =3.5; 95% CI, 1.5-8.2; P=0.004), and age (HR =1.0; 95% CI, 1.0-1.1; P=0.035). There were no significant differences between patients who did and did not receive adjuvant therapy following resection (all P>0.05). A second multivariable model included only those patients who received adjuvant therapy (n=39). Lack of inclusion of a platinum agent in the adjuvant regimen (HR =2.4; 95% CI, 1.0-5.8; P=0.040) and larger tumor diameter (HR =1.3; 95% CI, 1.0-1.6; P=0.047) were independent predictors of inferior survival. Conclusions Addition of a platinum agent to adjuvant regimens for resected PASC may improve survival among these high-risk patients, though collaborative prospective investigation is needed. PMID:25830031

  15. Chemotherapy

    MedlinePlus

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

  16. Differential Response of Immunohistochemically Defined Breast Cancer Subtypes to Anthracycline-Based Adjuvant Chemotherapy with or without Paclitaxel

    PubMed Central

    Fountzilas, George; Dafni, Urania; Bobos, Mattheos; Batistatou, Anna; Kotoula, Vassiliki; Trihia, Helen; Malamou-Mitsi, Vassiliki; Miliaras, Spyros; Chrisafi, Sofia; Papadopoulos, Savvas; Sotiropoulou, Maria; Filippidis, Theodoros; Gogas, Helen; Koletsa, Triantafyllia; Bafaloukos, Dimitrios; Televantou, Despina; Kalogeras, Konstantine T.; Pectasides, Dimitrios; Skarlos, Dimosthenis V.; Koutras, Angelos; Dimopoulos, Meletios A.

    2012-01-01

    Background The aim of the present study was to investigate the efficacy of adjuvant dose-dense sequential chemotherapy with epirubicin, paclitaxel, and CMF in subgroups of patients with high-risk operable breast cancer, according to tumor subtypes defined by immunohistochemistry (IHC). Materials and Methods Formalin-fixed paraffin-embedded (FFPE) tumor tissue samples from 1,039 patients participating in two adjuvant dose-dense sequential chemotherapy phase III trials were centrally assessed in tissue micro-arrays by IHC for 6 biological markers, that is, estrogen receptor (ER), progesterone receptor (PgR), HER2, Ki67, cytokeratin 5 (CK5), and EGFR. The majority of the cases were further evaluated for HER2 amplification by FISH. Patients were classified as: luminal A (ER/PgR-positive, HER2-negative, Ki67low); luminal B (ER/PgR-positive, HER2-negative, Ki67high); luminal-HER2 (ER/PgR-positive, HER2-positive); HER2-enriched (ER-negative, PgR-negative, HER2-positive); triple-negative (TNBC) (ER-negative, PgR-negative, HER2-negative); and basal core phenotype (BCP) (TNBC, CK5-positive and/or EGFR-positive). Results After a median follow-up time of 105.4 months the 5-year disease-free survival (DFS) and overall survival (OS) rates were 73.1% and 86.1%, respectively. Among patients with HER2-enriched tumors there was a significant benefit in both DFS and OS (log-rank test; p = 0.021 and p = 0.006, respectively) for those treated with paclitaxel. The subtype classification was found to be of both predictive and prognostic value. Setting luminal A as the referent category, the adjusted for prognostic factors HR for relapse for patients with TNBC was 1.91 (95% CI: 1.31–2.80, Wald's p = 0.001) and for death 2.53 (95% CI: 1.62–3.60, p<0.001). Site of and time to first relapse differed according to subtype. Locoregional relapses and brain metastases were more frequent in patients with TNBC, while liver metastases were more often seen in patients with HER2

  17. Impact of Postoperative Radiation Therapy on Survival in Patients With Complete Resection and Stage I, II, or IIIA Non-Small-Cell Lung Cancer Treated With Adjuvant Chemotherapy: The Adjuvant Navelbine International Trialist Association (ANITA) Randomized Trial

    SciTech Connect

    Douillard, Jean-Yves Rosell, Rafael; De Lena, Mario; Riggi, Marcello; Hurteloup, Patrick; Mahe, Marc-Andre

    2008-11-01

    Purpose: To study the impact of postoperative radiation therapy (PORT) on survival in the Adjuvant Navelbine International Trialist Association (ANITA) randomized study of adjuvant chemotherapy. Methods and Materials: ANITA is a randomized trial of adjuvant cisplatin and vinorelbine chemotherapy vs. observation in completely resected non-small-cell lung carcinoma (NSCLC) Stages IB to IIIA. Use of PORT was recommended for pN+ disease but was not randomized or mandatory. Each center decided whether to use PORT before initiation of the study. We describe here the survival of patients with and without PORT within each treatment group of ANITA. No statistical comparison of survival was performed because this was an unplanned subgroup analysis. Results: Overall, 232 of 840 patients received PORT (33.3% in the observation arm and 21.6% in the chemotherapy arm). In univariate analysis, PORT had a deleterious effect on the overall population survival. Patients with pN1 disease had an improved survival from PORT in the observation arm (median survival [MS] 25.9 vs. 50.2 months), whereas PORT had a detrimental effect in the chemotherapy group (MS 93.6 months and 46.6 months). In contrast, survival was improved in patients with pN2 disease who received PORT, both in the chemotherapy (MS 23.8 vs. 47.4 months) and observation arm (median 12.7 vs. 22.7 months). Conclusion: This retrospective evaluation suggests a positive effect of PORT in pN2 disease and a negative effect on pN1 disease when patients received adjuvant chemotherapy. The results support further evaluation of PORT in prospectively randomized studies in completely resected pN2 NSCLC.

  18. The effect of comorbidity on the use of adjuvant chemotherapy and type of regimen for curatively resected stage III colon cancer patients.

    PubMed

    Hsieh, Mei-Chin; Thompson, Trevor; Wu, Xiao-Cheng; Styles, Timothy; O'Flarity, Mary B; Morris, Cyllene R; Chen, Vivien W

    2016-05-01

    Postsurgical chemotherapy is guideline-recommended therapy for stage III colon cancer patients. Factors associated with patients not receiving adjuvant chemotherapy were identified in numerous studies; comorbidity was recognized as an important factor besides patient's age. We assessed the association between comorbidity and the use of adjuvant chemotherapy and type of chemotherapy regimen. Stage III colon cancer patients who underwent surgical resection were obtained from ten Centers for Disease Control and Prevention (CDC)-NPCR Specialized Registries which participated in the Comparative Effectiveness Research (CER) project. Comorbidity was classified into no comorbidity recorded, Charlson, non-Charlson comorbidities, number, and severity of Charlson comorbidity. Pearson chi-square test and multivariable logistic regression were employed. Of 3180 resected stage III colon cancer patients, 64% received adjuvant chemotherapy. After adjusting for patient's demographic and tumor characteristics, there were no significant differences in receipt of chemotherapy between Charlson and non-Charlson comorbidity. However, patients who had two or more Charlson comorbidities or had moderate to severe disease were significantly less likely to have chemotherapy (ORs 0.69 [95% CI, 0.51-0.92] and 0.62 [95% CI, 0.42-0.91], respectively) when compared with those with non-Charlson comorbidity. In addition, those with moderate or severe comorbidities were more likely to receive single chemotherapy agent (P < 0.0001). Capecitabine and FOLFOX were the most common single- and multi-agent regimens regardless of type of comorbidity grouping. Both the number and severity of comorbidity were significantly associated with receipt of guideline-recommended chemotherapy and type of agent in stage III resected colon cancer patients. Better personalized care based on individual patient's condition ought to be recognized. PMID:26773804

  19. Prognostic Role of BRAF Mutation in Stage II/III Colorectal Cancer Receiving Curative Resection and Adjuvant Chemotherapy: A Meta-Analysis Based on Randomized Clinical Trials

    PubMed Central

    Cao, Ying; Fang, Xuefeng; Zhong, Chenhan; Li, Dan; Yuan, Ying

    2016-01-01

    Background and Objective Studies examining the prognostic value of the BRAF mutation on relapse-free survival (RFS), disease-free survival (DFS) and overall survival (OS) in stage II/III colorectal cancer (CRC) patients receiving curative resection and adjuvant chemotherapy so far showed discrepant results. Therefore, a meta-analysis of relevant studies was performed for clarification. Methods Randomized trials of stage II/III colorectal cancer treated with curative resection followed by adjuvant chemotherapy were selected to conduct a meta-analysis. The necessary descriptive and statistical information such as hazard ratios (HRs) and 95% confidence intervals (CIs) were derived from published survival data. Results Seven phase III randomized clinical trials (RCTs) including 1,035 BRAF mutation stage II/III CRC patients receiving curative resection and adjuvant chemotherapy were analyzed. Overall, BRAF mutation resulted in poorer OS (HR = 1.42, 95% CI: 1.25–1.60; P < 0.00001), and poorer DFS (HR = 1.26, 95% CI: 1.07–1.48, P = 0.006) compared with BRAF wild-type CRC. The prognostic role on RFS could not be elucidated in the meta-analysis because of limited data. Conclusions BRAF mutation was significantly related with shorter DFS and OS among stage II/III CRC patients receiving adjuvant chemotherapy after curative resection. Its prognostic role for RFS needs to be further analyzed when more data is available. PMID:27138801

  20. The Development of a Mindfulness-Based Music Therapy (MBMT) Program for Women Receiving Adjuvant Chemotherapy for Breast Cancer.

    PubMed

    Lesiuk, Teresa

    2016-01-01

    Problems with attention and symptom distress are common clinical features reported by women who receive adjuvant chemotherapy for breast cancer. Mindfulness practice significantly improves attention and mindfulness programs significantly reduce symptom distress in patients with cancer, and, more specifically, in women with breast cancer. Recently, a pilot investigation of a music therapy program, built on core attitudes of mindfulness practice, reported significant benefits of enhanced attention and decreased negative mood and fatigue in women with breast cancer. This paper delineates the design and development of the mindfulness-based music therapy (MBMT) program implemented in that pilot study and includes clients' narrative journal responses. Conclusions and recommendations, including recommendation for further exploration of the function of music in mindfulness practice are provided. PMID:27517966

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

    PubMed Central

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

    2014-01-01

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

  2. Stage III Colon Cancer: The Individualized Strategy of Adjuvant Chemotherapy for Aged Under and Over 70

    PubMed Central

    Lu, Chieh-Sheng; Chang, Ping-Ying; Chen, Yu-Guang; Chen, Jia-Hong; Wu, Yi-Ying; Ho, Ching-Liang

    2015-01-01

    Background The aim of this study was to examine the specific chemoregimens selected for adjuvant therapy in the patients with stage III colon cancer. We investigated the trends in chemotherapeutic prescribing patterns and looked for adequate therapeutic setting for these patients. Methods 288 patients presenting with stage III colon cancer and undergoing adjuvant therapies after curative surgery for more than 3-month were enrolled between January 2006 and December 2011. Demographic characteristics and therapeutic factors were analyzed, including age, gender, histological grade, tumor sizes, tumor location, pathologic stage, performance status, serum carcinoembryonic antigen, regimens selection, interval from the operation to the start of adjuvant therapy and prolonged adjuvant therapy. Kaplan– Meier methods were utilized for drawing survival curves and Cox model was used to analyze survival, prognostic factors. Results The analysis showed that the patients aged under 70 received more intensive therapies than those aged over 70 (P<0.001). Later, advanced analysis in therapeutic factors was conducted between the patients aged under 70 and those over 70. In the patients aged under 70, significant differences in 4-year overall survival (OS) were noted between UFUR (oral tegafur-uracil plus leucovorin) groups and FOLFOX (5-FU plus oxaliplatin) [65.6% versus (vs) 89.8%, relative risk (RR) 3.780, 95% confidence interval (CI) 1.263–11.315, P = 0.017]. There were also differences in 4-year OS between these patients with and without oxaliplatin-contained regimens (92.1% vs 83.4%, respectively, RR 0.385, 95% CI 0.157–0.946, P = 0.037). In addition, the patients who received intravenous or combined therapy also had higher 4-year OS than those only received oral regimens (92.1% vs 76.6%, P = 0.077), though the finding did not reach statistical significance. In contrast to the survival benefits of above therapeutic settings for the patients aged under 70, there was less

  3. Mastectomy With Immediate Expander-Implant Reconstruction, Adjuvant Chemotherapy, and Radiation for Stage II-III Breast Cancer: Treatment Intervals and Clinical Outcomes

    SciTech Connect

    Wright, Jean L.; Cordeiro, Peter G.; Ben-Porat, Leah; Van Zee, Kimberly J.; Hudis, Clifford; Beal, Kathryn; McCormick, Beryl

    2008-01-01

    Purpose: To determine intervals between surgery and adjuvant chemotherapy and radiation in patients treated with mastectomy with immediate expander-implant reconstruction, and to evaluate locoregional and distant control and overall survival in these patients. Methods and Materials: Between May 1996 and March 2004, 104 patients with Stage II-III breast cancer were routinely treated at our institution under the following algorithm: (1) definitive mastectomy with axillary lymph node dissection and immediate tissue expander placement, (2) tissue expansion during chemotherapy, (3) exchange of tissue expander for permanent implant, (4) radiation. Patient, disease, and treatment characteristics and clinical outcomes were retrospectively evaluated. Results: Median age was 45 years. Twenty-six percent of patients were Stage II and 74% Stage III. All received adjuvant chemotherapy. Estrogen receptor staining was positive in 77%, and 78% received hormone therapy. Radiation was delivered to the chest wall with daily 0.5-cm bolus and to the supraclavicular fossa. Median dose was 5040 cGy. Median interval from surgery to chemotherapy was 5 weeks, from completion of chemotherapy to exchange 4 weeks, and from exchange to radiation 4 weeks. Median interval from completion of chemotherapy to start of radiation was 8 weeks. Median follow-up was 64 months from date of mastectomy. The 5-year rate for locoregional disease control was 100%, for distant metastasis-free survival 90%, and for overall survival 96%. Conclusions: Mastectomy with immediate expander-implant reconstruction, adjuvant chemotherapy, and radiation results in a median interval of 8 weeks from completion of chemotherapy to initiation of radiation and seems to be associated with acceptable 5-year locoregional control, distant metastasis-free survival, and overall survival.

  4. Prospective randomized trial of early postoperative intraperitoneal chemotherapy as an adjuvant to resectable gastric cancer.

    PubMed Central

    Yu, W; Whang, I; Suh, I; Averbach, A; Chang, D; Sugarbaker, P H

    1998-01-01

    OBJECTIVE: Surgeons have postulated on numerous occasions that cancer resection may participate in the dissemination of a malignancy. This randomized trial sought to determine whether a large volume of chemotherapy solution used perioperatively to flood the peritoneal cavity could eliminate microscopic residual disease and thereby improve survival of patients with gastric cancer. SUMMARY BACKGROUND DATA: Surgical treatment failures in patients with gastric cancer are confined to the abdomen in most patients. Resection site and peritoneal surface spread, along with liver metastases, are the most common areas of recurrence. Survival and quality of life of patients with gastric cancer would be improved if disease progression at these anatomic sites was reduced. METHODS: In a prospective randomized trial of 248 patients, intraperitoneal mitomycin C on day 1 and intraperitoneal 5-fluorouracil on days 2 through 5 were administered after gastric cancer resection. Patients who were thought to have stage II or stage III disease were randomized after resection to surgery alone versus surgery plus early postoperative intraperitoneal chemotherapy. After final pathologic examinations, there were 39 patients with stage I, 50 with stage II 95 with stage III, and 64 with resected stage IV cancer. RESULTS: The 5-year survival of the surgery-only group was 29.3%, and the surgery-plus-intraperitoneal chemotherapy group was 38.7% (p = 0.219). In a subset analysis, the patients with stage I, stage II, and stage IV disease showed no statistically significant difference in survival. The 5-year survival rate of patients with stage III disease who underwent surgery only was 18.4% versus a survival rate of 49.1% for patients who underwent surgery plus intraperitoneal chemotherapy (p = 0.011). CONCLUSIONS: In a subset analysis, patients with stage III gastric cancer have shown a statistically significant improvement in survival when treated with perioperative intraperitoneal chemotherapy

  5. Assessment of the Relation between the Expression of Oxaliplatin Transporters in Colorectal Cancer and Response to FOLFOX-4 Adjuvant Chemotherapy: A Case Control Study

    PubMed Central

    Le Roy, Bertrand; Tixier, Lucie; Pereira, Bruno; Sauvanet, Pierre; Buc, Emmanuel; Pétorin, Caroline; Déchelotte, Pierre; Pezet, Denis; Balayssac, David

    2016-01-01

    Background Adjuvant chemotherapy for colorectal cancer is mainly based on the combination of 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX-4). The pharmacological target of oxaliplatin remains intracellular and therefore dependent on its entry into cells. The intracellular distribution of oxaliplatin is mediated by organic cation transporters 1, 2 and 3 (OCT1, 2 and 3), copper transporter 1 (CTR1) and ATPase Cu2+ transporting beta polypeptide (ATP7B) and may modulate the efficacy of oxaliplatin-based chemotherapy. The aim of this study was to perform a retrospective study to assess the relation between the expression of oxaliplatin transporters in colorectal cancer before chemotherapy and the response to FOLFOX-4 adjuvant chemotherapy in responder and non-responder patients. Methods This retrospective study was conducted at a single center (University Hospital of Clermont-Ferrand, France). The target population was patients with resectable colorectal cancer operated between 2006 and 2013. Inclusion criteria were defined for the responder patients as no cancer recurrence 3 years after the end of chemotherapy, and for the non-responder patients as cancer recurrence within 1 year. Other inclusion criteria were stages IIb–IV cancers, first-line adjuvant FOLFOX-4 chemotherapy, and the availability of resected primary tumor samples. Exclusion criteria were preoperative chemotherapy and/or radiotherapy, a targeted therapy, other anticancer drugs, cancer recurrence between the first and the third year after the end of chemotherapy and follow-up < 3 years. Immunostaining of oxaliplatin transporters (OCT1, 2, 3, CTR1 and ATP7B) and Ki-67 was assessed in tumor samples. Results Retrospectively, 31 patients have been selected according to inclusion and exclusion criteria (15 responders and 16 non-responders). Before FOLFOX-4 regimen, OCT3 expression was significantly lower in responder patients compared to non-responders (p<0.001). According to multivariate analysis

  6. A phase II study evaluating neo-/adjuvant EIA chemotherapy, surgical resection and radiotherapy in high-risk soft tissue sarcoma

    PubMed Central

    2011-01-01

    Abstract Background The role of chemotherapy in high-risk soft tissue sarcoma is controversial. Though many patients undergo initial curative resection, distant metastasis is a frequent event, resulting in 5-year overall survival rates of only 50-60%. Neo-adjuvant and adjuvant chemotherapy (CTX) has been applied to achieve pre-operative cytoreduction, assess chemosensitivity, and to eliminate occult metastasis. Here we report on the results of our non-randomized phase II study on neo-adjuvant treatment for high-risk STS. Method Patients with potentially curative high-risk STS (size ≥ 5 cm, deep/extracompartimental localization, tumor grades II-III [FNCLCC]) were included. The protocol comprised 4 cycles of neo-adjuvant chemotherapy (EIA, etoposide 125 mg/m2 iv days 1 and 4, ifosfamide 1500 mg/m2 iv days 1 - 4, doxorubicin 50 mg/m2 day 1, pegfilgrastim 6 mg sc day 5), definitive surgery with intra-operative radiotherapy, adjuvant radiotherapy and 4 adjuvant cycles of EIA. Result Between 06/2005 and 03/2010 a total of 50 subjects (male = 33, female = 17, median age 50.1 years) were enrolled. Median follow-up was 30.5 months. The majority of primary tumors were located in the extremities or trunk (92%), 6% originated in the abdomen/retroperitoneum. Response by RECIST criteria to neo-adjuvant CTX was 6% CR (n = 3), 24% PR (n = 12), 62% SD (n = 31) and 8% PD (n = 4). Local recurrence occurred in 3 subjects (6%). Distant metastasis was observed in 12 patients (24%). Overall survival (OS) and disease-free survival (DFS) at 2 years was 83% and 68%, respectively. Multivariate analysis failed to prove influence of resection status or grade of histological necrosis on OS or DFS. Severe toxicities included neutropenic fever (4/50), cardiac toxicity (2/50), and CNS toxicity (4/50) leading to CTX dose reductions in 4 subjects. No cases of secondary leukemias were observed so far. Conclusion The current protocol is feasible for achieving local control rates, as well as OS and

  7. Postoperative Radiotherapy for Pathologic N2 Non–Small-Cell Lung Cancer Treated With Adjuvant Chemotherapy: A Review of the National Cancer Data Base

    PubMed Central

    Robinson, Cliff G.; Patel, Aalok P.; Bradley, Jeffrey D.; DeWees, Todd; Waqar, Saiama N.; Morgensztern, Daniel; Baggstrom, Maria Q.; Govindan, Ramaswamy; Bell, Jennifer M.; Guthrie, Tracey J.; Colditz, Graham A.; Crabtree, Traves D.; Kreisel, Daniel; Krupnick, Alexander S.; Patterson, G. Alexander; Meyers, Bryan F.; Puri, Varun

    2015-01-01

    Purpose To investigate the impact of modern postoperative radiotherapy (PORT) on overall survival (OS) for patients with N2 non–small-cell lung cancer (NSCLC) treated nationally with surgery and adjuvant chemotherapy. Patients and Methods Patients with pathologic N2 NSCLC who underwent complete resection and adjuvant chemotherapy from 2006 to 2010 were identified from the National Cancer Data Base and stratified by use of PORT (≥ 45 Gy). A total of 4,483 patients were identified (PORT, n = 1,850; no PORT, n = 2,633). The impact of patient and treatment variables on OS was explored using Cox regression. Results Median follow-up time was 22 months. On univariable analysis, improved OS correlated with younger age, treatment at an academic facility, female sex, urban population, higher income, lower Charlson comorbidity score, smaller tumor size, multiagent chemotherapy, resection with at least a lobectomy, and PORT. On multivariable analysis, improved OS remained independently predicted by younger age, female sex, urban population, lower Charlson score, smaller tumor size, multiagent chemotherapy, resection with at least a lobectomy, and PORT (hazard ratio, 0.886; 95% CI, 0.798 to 0.988). Use of PORT was associated with an increase in median and 5-year OS compared with no PORT (median OS, 45.2 v 40.7 months, respectively; 5-year OS, 39.3% [95% CI, 35.4% to 43.5%] v 34.8% [95% CI, 31.6% to 38.3%], respectively; P = .014). Conclusion For patients with N2 NSCLC after complete resection and adjuvant chemotherapy, modern PORT seems to confer an additional OS advantage beyond that achieved with adjuvant chemotherapy alone. PMID:25667283

  8. A prospective cohort study of early discontinuation of adjuvant chemotherapy in women with breast cancer: the breast cancer quality of care study (BQUAL).

    PubMed

    Neugut, Alfred I; Hillyer, Grace Clarke; Kushi, Lawrence H; Lamerato, Lois; Buono, Donna L; Nathanson, S David; Bovbjerg, Dana H; Mandelblatt, Jeanne S; Tsai, Wei-Yann; Jacobson, Judith S; Hershman, Dawn L

    2016-07-01

    For many women with non-metastatic breast cancer, adjuvant chemotherapy prevents recurrence and extends survival. Women who discontinue chemotherapy early may reduce those benefits, but little is known about what predicts early discontinuation. We sought to determine prospectively the rate and reasons for early discontinuation of adjuvant chemotherapy in women with breast cancer. We conducted a prospective cohort study among three U.S. health care organizations. Of 1158 women with newly diagnosed non-metastatic breast cancer, 2006-2010, we analyzed 445 (38.4 %) patients who initiated standard adjuvant chemotherapy as defined by accepted guidelines. We interviewed patients at baseline and twice during treatment regarding sociodemographic/psychosocial factors and treatment decision-making and collected clinical data. They were categorized according to the number of cycles required by the chemotherapy regimen they had initiated. The outcome was early discontinuation (<80 % of planned cycles). Of patients analyzed, 392 (88.1 %) completed the prescribed therapy. The strongest predictor was receipt of a regimen entailing >4 cycles of therapy (18.1 % for longer regimens, 7.4 % for 4 cycles) (odds ratio [OR] 2.59, 95 % CI 1.32-5.08), controlling for race, age, stage, hormone receptor status, social support, optimism, spirituality, stress, and physical symptoms. Higher levels of psychological symptoms on the Memorial symptom assessment scale also increased the odds of early discontinuation (OR 1.92, 95 % CI 0.998-3.68). The large majority of patients who initiated adjuvant chemotherapy for breast cancer completed their prescribed regimens, but early discontinuation was associated with lengthier regimens and, with borderline statistical significance, for those with psychological side effects. PMID:27287779

  9. Effects of postoperative adjuvant chemotherapy and radiotherapy on ovarian function in women undergoing treatment for soft tissue sarcoma

    SciTech Connect

    Shamberger, R.C.; Sherins, R.J.; Ziegler, J.L.; Glatstein, E.; Rosenberg, S.A.

    1981-12-01

    Ovarian function was evaluated in 11 women 16 to 43 years of age at treatment who received doxorubicin, cyclophosphamide, and high doses of methotrexate with or without radiotherapy in adjuvant therapy of soft tissue sarcoma. Five women (16-33 yr old) who received chemotherapy alone or combined with radiotherapy only at sites distant from the ovaries (chest wall, thigh, and leg) had minimal menstrual irregularities or temporary cessation of menses during therapy; cyclic menses returned promptly after therapy. Gonadotropin levels (expressed as means +/- SD (follicle-stimulating hormone (FSH), 10 +/- 5 mlU/ml; luteinizing hormone (LH), 10 +/- 4 mlU/ml) and 17 beta-estradiol (E2) levels (means +/- SD, 208 +/- 147 pg/ml) were normal. By contrast, 4 older women (ages 36-43 yr) who received similar treatment developed persistent amenorrhea with postmenopausal levels of gonadotropin (FSH, 108 +/- 29 mlU/ml; LH, 72 +/- 19 mlU/ml) and E2 (19 +/- 8 pg/ml). Two additional women (ages 21 and 39 yr) who received radiation (7,000 rad) to the pelvis plus chemotherapy developed prompt cessation of menses and became functional castrates (FSH, 77 and 80 mlU/ml; LH, 40 and 58 mlU/ml; E2, 10 and 19 pg/ml). However, this result would be expected from the radiation dose alone. The data demonstrated that ovarian dysfunction may follow the use of doxorubicin, cyclophosphamide, and high doses of methotrexate and that the injury is age related.

  10. Neo-adjuvant chemotherapy plus surgery versus surgery alone for cervical cancer: Meta-analysis of randomized controlled trials.

    PubMed

    Peng, Yun-Hua; Wang, Xin-Xiu; Zhu, Jing-Song; Gao, Li

    2016-02-01

    The aim of this study was to evaluate the efficacy and safety of neo-adjuvant chemotherapy (NACT) versus radical surgery (RS) for patients with cervical cancer. A meta-analysis of randomized controlled trials (RCT) of NACT + RS versus RS alone for patients with cervical cancer was performed according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. The following electronic databases were searched from their inception to April 2015: PUBMED, EMBASE and Cochrane Library. Statistical analysis was done using REVIEW MANAGER 5.3. Five RCT involving 739 patients were studied. There were significant differences between the NACT + RS and the RS-alone groups for positive lymph nodes (OR, 0.45; 95%CI: 0.29-0.70) and parametrial infiltration (OR, 0.48; 95% CI: 0.25-0.92), while treatment efficacy did not differ significantly for 5-year overall survival rate (OR, 1.17; 95% CI: 0.85-1.61), 5-year disease-free survival rate (OR, 1.09; 95% CI: 0.77-1.56) or recurrence rate (OR, 1.17; 95% CI: 0.85-1.61). The results also indicated that chemotherapy-related toxicity was well tolerated. For patients with cervical cancer, NACT could significantly reduce the number of positive lymph nodes and the level of parametrial infiltration compared with RS alone, and be well tolerated. PMID:26807961

  11. Neoadjuvant and adjuvant chemotherapy combined with anatomical resection of feline injection-site sarcoma: results in 21 cats.

    PubMed

    Bray, J; Polton, G

    2016-06-01

    This study assesses the outcome of two combined treatment strategies for the treatment of feline injection-site sarcoma (FISS). Twenty-one cats with primary or recurrent FISS received 3 cycles of neoadjuvant chemotherapy with epirubicin (25 mg m(-2) ), then an anatomical resection of the entire muscle compartment containing the tumour was performed based on the findings of co-axial imaging. Cats then received a further 3 cycles of adjuvant chemotherapy. Follow-up was performed by telephone contact with a median follow-up time of 1072 days. Three cats (14%) developed local tumour recurrence at days 264, 664 and 1573 after surgery. A median survival time could not be calculated as over 80% of the study population remained alive or were censored due to death from other causes. When compared to historical controls, the results of this study demonstrate superior rates of tumour-free survival and disease-free interval. PMID:24502401

  12. Adjuvant systemic chemotherapy with or without bevacizumab in patients with resected pulmonary metastases from colorectal cancer

    PubMed Central

    Turan, Nedim; Benekli, Mustafa; Dane, Faysal; Unal, Olcun Umit; Kara, Hasan Volkan; Koca, Dogan; Balvan, Ozlem; Eren, Tulay; Tastekin, Didem; Helvaci, Kaan; Berk, Veli; Demirci, Umut; Ozturk, Selcuk Cemil; Dogan, Erkan; Cetin, Bulent; Kucukoner, Mehmet; Tonyali, Onder; Tufan, Gulnihal; Oztop, Ilhan; Gumus, Mahmut; Coskun, Ugur; Uner, Aytug; Ozet, Ahmet; Buyukberber, Suleyman

    2014-01-01

    Introduction We investigated the impact of modern chemotherapy regimens and bevacizumab following pulmonary metastasectomy (PM) from metastatic colorectal cancer (CRC). Methods A total of 122 consecutive patients who were curatively resected for pulmonary metastases of CRC in twelve oncology centers were retrospectively analysed between January 2000 and April 2012. Results Of 122 patients, 14 did not receive any treatment following PM. The remaining 108 patients received fluoropyrimidine-based (n = 12), irinotecan-based (n = 56) and oxaliplatin-based (n = 40) chemotherapy combinations. Among these, 52 patients received bevacizumab (BEV) while 56 did not (NoBEV). Median recurrence-free survival (RFS) was 17 months and median overall survival (OS) has not been reached at a median follow-up of 25 months after PM. Three and five-year OS rates were 66% and 53%, respectively. RFS and OS were similar, irrespective of the chemotherapy regimen or BEV use. Positive pulmonary margin, KRAS mutation status, and previous liver metastasectomy were negative independent prognostic factors for RFS, while pathologically confirmed thoracic lymph node involvement was the only negative independent prognostic for OS in multivariate analysis. Conclusions No significant RFS or OS difference was observed in respect to chemotherapy regimens with or without BEV in patients with pulmonary metastases of CRC following curative resection. PMID:26763794

  13. Robotic Stereotactic Radioablation Concomitant With Neo-Adjuvant Chemotherapy for Breast Tumors

    SciTech Connect

    Bondiau, Pierre-Yves; Bahadoran, Phillipe; Lallement, Michel; Birtwisle-Peyrottes, Isabelle; Chapellier, Claire; Chamorey, Emmanuel; Courdi, Adel; Quielle-Roussel, Catherine; Thariat, Juliette; Ferrero, Jean-Marc

    2009-11-15

    Purpose: Robotic stereotactic radioablation (RSR) allows stereotactic irradiation of thoracic tumors; however, it has never been used for breast tumors and may have a real potential. We conducted a Phase I study, including neoadjuvant chemotherapy (NACT), a two-level dose-escalation study (6.5 Gy x 3 fractions and 7.5 Gy x 3 fractions) using RSR and breast-conserving surgery followed by conventional radiotherapy. Materials and Methods: To define toxicity, we performed a dermatologic exam (DE) including clinical examination by two independent observers and technical examination by colorimetry, dermoscopy, and skin ultrasound. DE was performed before NACT (DE0), at 36 days (DE1), at 56 days (DE2), after the NACT treatment onset, and before surgery (DE3). Surgery was performed 4-8 weeks after the last chemotherapy session. A pathologic examination was also performed. Results: There were two clinical complete responses and four clinical partial responses at D56 and D85. Maximum tolerable dose was not reached. All patients tolerated RSR with no fatigue; 2 patients presented with mild pain after the third fraction of the treatment. There was no significant toxicity measured with ultrasound and dermoscopy tests. Postoperative irradiation (50 Gy) has been delivered without toxicity. Conclusion: The study showed the feasibility of irradiation with RSR combined with chemotherapy and surgery for breast tumors. There was no skin toxicity at a dose of 19.5 Gy or 22.5 Gy delivered in three fractions combined with chemotherapy. Lack of toxicity suggested that the dose could be increased further. Pathologic response was acceptable.

  14. Brief chemotherapy (Stanford V) and adjuvant radiotherapy for bulky or advanced Hodgkin's disease: an update.

    PubMed

    Horning, S J; Rosenberg, S A; Hoppe, R T

    1996-01-01

    From May 1989 to August 1995, 94 previously untreated patients with Hodgkin's disease stage II with bulky mediastinal involvement (n = 28) or stage III or IV (n = 66) received an abbreviated chemotherapy regimen, Stanford V, +/-radiotherapy (RT). Chemotherapy was given weekly for 12 weeks followed by consolidative RT to sites of initial bulky disease. With a median follow-up of 3 years, the actuarial 6-year survival is 93% and the freedom from progression is 89%. There have been no relapses or deaths among the 28 patients with stage II bulky mediastinal disease. Eight relapses and three deaths have occurred in the group of 66 patients with stage III-IV disease. The abbreviated chemotherapy regimen, Stanford V, in combination with RT is well tolerated and highly effective therapy for bulky, limited stage and advanced stage HD. Lower cumulative exposure to alkylating agents, doxorubicin, bleomycin and limited use of radiation is expected to improved the prospects for fertility and decrease the risks for second neoplasms and late cardiopulmonary toxicity. PMID:8836420

  15. PTK7 as a potential prognostic and predictive marker of response to adjuvant chemotherapy in breast cancer patients, and resistance to anthracycline drugs.

    PubMed

    Ataseven, Beyhan; Gunesch, Angela; Eiermann, Wolfgang; Kates, Ronald E; Högel, Bernhard; Knyazev, Pjotr; Ullrich, Axel; Harbeck, Nadia

    2014-01-01

    Biomarkers predicting resistance to particular chemotherapy regimens could play a key role in optimally individualized treatment concepts. PTK7 (protein tyrosine kinase 7) belongs to the receptor tyrosine kinase family involved in several physiological, but also malignant, cell behaviors. Recent studies in acute myeloid leukemia have associated PTK7 expression with resistance to anthracycline therapy. PTK7 mRNA expression in primary tumor tissue (PTT) and corresponding lymph node tissue (LNT) were retrospectively measured in 117 patients with early breast cancer; PTK7 expression was available in 103 PTT and 108 LNT samples. Median age was 60 years (range, 27-87 years). At a median follow-up of 28.5 months, 6 deaths and 16 recurrences had occurred. PTK7 expression correlations with clinicopathological features were computed and PTK7 expression effects on patient outcome were analyzed in three cohorts defined by adjuvant treatment: anthracycline-based treatment, other chemotherapy regimens (including taxane or other substances), or no chemotherapy. Association of PTK7 expression with clinicopathological features was seen only for age in PTT and nodal stage in LNT. High LN PTK7 was associated with poorer disease-free survival (DFS) in the total population (3-year DFS: low [81.7%] versus high [70.4%]; P=0.016) and in patients without adjuvant chemotherapy (3-year DFS: low [91.7%] versus high [22.3%]; P<0.001), but not in patients receiving adjuvant chemotherapy (P=0.552). DFS stratified by PTK7 expression was compared in treatment cohorts: In patients with low LN PTK7 expression, neither chemotherapy cohort showed significantly better survival than the no-chemotherapy cohort. In patients with high LN PTK7 expression, those receiving chemotherapy, including substances other than anthracyclines, but not those receiving only anthracycline-based chemotherapy, showed significantly better DFS than those receiving no chemotherapy (P=0.001). Our results support earlier

  16. PTK7 as a potential prognostic and predictive marker of response to adjuvant chemotherapy in breast cancer patients, and resistance to anthracycline drugs

    PubMed Central

    Ataseven, Beyhan; Gunesch, Angela; Eiermann, Wolfgang; Kates, Ronald E; Högel, Bernhard; Knyazev, Pjotr; Ullrich, Axel; Harbeck, Nadia

    2014-01-01

    Biomarkers predicting resistance to particular chemotherapy regimens could play a key role in optimally individualized treatment concepts. PTK7 (protein tyrosine kinase 7) belongs to the receptor tyrosine kinase family involved in several physiological, but also malignant, cell behaviors. Recent studies in acute myeloid leukemia have associated PTK7 expression with resistance to anthracycline therapy. PTK7 mRNA expression in primary tumor tissue (PTT) and corresponding lymph node tissue (LNT) were retrospectively measured in 117 patients with early breast cancer; PTK7 expression was available in 103 PTT and 108 LNT samples. Median age was 60 years (range, 27–87 years). At a median follow-up of 28.5 months, 6 deaths and 16 recurrences had occurred. PTK7 expression correlations with clinicopathological features were computed and PTK7 expression effects on patient outcome were analyzed in three cohorts defined by adjuvant treatment: anthracycline-based treatment, other chemotherapy regimens (including taxane or other substances), or no chemotherapy. Association of PTK7 expression with clinicopathological features was seen only for age in PTT and nodal stage in LNT. High LN PTK7 was associated with poorer disease-free survival (DFS) in the total population (3-year DFS: low [81.7%] versus high [70.4%]; P=0.016) and in patients without adjuvant chemotherapy (3-year DFS: low [91.7%] versus high [22.3%]; P<0.001), but not in patients receiving adjuvant chemotherapy (P=0.552). DFS stratified by PTK7 expression was compared in treatment cohorts: In patients with low LN PTK7 expression, neither chemotherapy cohort showed significantly better survival than the no-chemotherapy cohort. In patients with high LN PTK7 expression, those receiving chemotherapy, including substances other than anthracyclines, but not those receiving only anthracycline-based chemotherapy, showed significantly better DFS than those receiving no chemotherapy (P=0.001). Our results support earlier

  17. Eradication of breast cancer with bone metastasis by autologous formalin-fixed tumor vaccine (AFTV) combined with palliative radiation therapy and adjuvant chemotherapy: a case report.

    PubMed

    Kuranishi, Fumito; Ohno, Tadao

    2013-01-01

    Skeletal metastasis of breast carcinoma is refractory to intensive chemo-radiation therapy and therefore is assumed impossible to cure. Here, we report an advanced case of breast cancer with vertebra-Th7 metastasis that showed complete response to combined treatments with formalin-fixed autologous tumor vaccine (AFTV), palliative radiation therapy with 36 Gy, and adjuvant chemotherapy with standardized CEF (cyclophosphamide, epirubicin, and 5FU), zoledronic acid, and aromatase inhibitors following mastectomy for the breast tumor. The patient has been disease-free for more than 4 years after the mammary surgery and remains well with no evidence of metastasis or local recurrence. Thus, a combination of AFTV, palliative radiation therapy, and adjuvant chemotherapy may be an effective treatment for this devastating disease. PMID:23734861

  18. Effects of postoperative adjuvant chemotherapy and radiotherapy on ovarian function in women undergoing treatment for soft tissue sarcoma

    SciTech Connect

    Shamberger, R.C.; Sherins, R.J.; Ziegler, J.L.; Glatstein, E.; Rosenberg, S.A.

    1981-12-01

    Ovarian function was evaluated in 11 women 16 to 43 years of age at treatment who received doxorubicin, cyclophosphamide, and high doses of methotrexate with or without radiotherapy in adjuvant therapy of soft tissue sarcoma. Five women (16-33 yr old) who received chemotherapy alone or combined with radiotherapy only at sites distant from the ovaries (chest wall, thigh, and leg) had minimal menstrual irregularities or temporary cessation of menses during therapy; cyclic menses returned promptly after therapy. Gonadotropin levels (expressed as means +/- SD) (follicle-stimulating hormone (FSH), 10 +/- 15 mlU/ml; luteinizing hormone (LH), 10 +/- 4 mlU/ml) and 17 ..beta..-estradiol (E/sub 2/) levels (means +/- SD, 208 +/- 147 pg/ml) were normal. By contrast, 4 older women (ages 36-43 yr) who received similar treatment developd persistent amenorrhea with postmenopausal levels of gonadotropin (FSH, 109 +/- 29 mlU/ml; LH, 72 +/- 19 mlU/ml) and E/sub 2/ (19 +/- 8 pg/ml). Two additional women (ages 21 and 39 yr) who received radiation (7000 rad) to the pelvis plus chemotherapy developed prompt cessation of menses and became functional castrates (FSH, 77 and 80mlU/ml; LH, 40 and 58 mlU/ml; E/sub 2/, 10 and 19 pg/ml). However, this result would be expected from the radiation dose alone. The data demonstrated that ovarian dysfunction may follow the use of doxorubicin, cyclophosphamide, and high doses of methotrexate and that the injury is age related.

  19. Adjuvant chemotherapy for colon cancer: a consensus statement of the Hellenic and Cypriot Colorectal Cancer Study Group by the HeSMO.

    PubMed

    Kountourakis, Panteleimon; Souglakos, John; Gouvas, Nikolaos; Androulakis, Nikolaos; Athanasiadis, Athanasios; Boukovinas, Ioannis; Christodoulou, Christos; Chrysou, Evangelia; Dervenis, Christos; Emmanouilidis, Christos; Georgiou, Panagiotis; Karachaliou, Niki; Katopodi, Ourania; Makatsoris, Thomas; Papakostas, Pavlos; Pentheroudakis, Georgios; Pilpilidis, Ioannis; Sgouros, Joseph; Tekkis, Paris; Triantopoulou, Charina; Tzardi, Maria; Vassiliou, Vassilios; Vini, Louiza; Xynogalos, Spyridon; Xynos, Evaghelos; Ziras, Nikolaos; Papamichael, Demetris

    2016-01-01

    Colorectal cancer remains a major cause of cancer mortality in the Western world both in men and women. In this manuscript a concise overview and recommendations on adjuvant chemotherapy in colon cancer are presented. An executive team from the Hellenic Society of Medical Oncology was assigned to develop a consensus statement and guidelines on the adjuvant treatment of colon cancer. Fourteen statements on adjuvant treatment were subjected to the Delphi methodology. Voting experts were 68. All statements achieved a rate of consensus above than 80% (>87%) and none revised and entered to a second round of voting. Three and 8 of them achieved a 100 and an over than 90% consensus, respectively. These statements describe evaluations of therapies in clinical practice. They could be considered as general guidelines based on best available evidence for assistance in treatment decision-making. Furthermore, they serve to identify questions and targets for further research and the settings in which investigational therapy could be considered. PMID:26751386

  20. Adjuvant chemotherapy for colon cancer: a consensus statement of the Hellenic and Cypriot Colorectal Cancer Study Group by the HeSMO*

    PubMed Central

    Kountourakis, Panteleimon; Souglakos, John; Gouvas, Nikolaos; Androulakis, Nikolaos; Athanasiadis, Athanasios; Boukovinas, Ioannis; Christodoulou, Christos; Chrysou, Evangelia; Dervenis, Christos; Emmanouilidis, Christos; Georgiou, Panagiotis; Karachaliou, Niki; Katopodi, Ourania; Makatsoris, Thomas; Papakostas, Pavlos; Pentheroudakis, Georgios; Pilpilidis, Ioannis; Sgouros, Joseph; Tekkis, Paris; Triantopoulou, Charina; Tzardi, Maria; Vassiliou, Vassilios; Vini, Louiza; Xynogalos, Spyridon; Xynos, Evaghelos; Ziras, Nikolaos; Papamichael, Demetris

    2016-01-01

    Colorectal cancer remains a major cause of cancer mortality in the Western world both in men and women. In this manuscript a concise overview and recommendations on adjuvant chemotherapy in colon cancer are presented. An executive team from the Hellenic Society of Medical Oncology was assigned to develop a consensus statement and guidelines on the adjuvant treatment of colon cancer. Fourteen statements on adjuvant treatment were subjected to the Delphi methodology. Voting experts were 68. All statements achieved a rate of consensus above than 80% (>87%) and none revised and entered to a second round of voting. Three and 8 of them achieved a 100 and an over than 90% consensus, respectively. These statements describe evaluations of therapies in clinical practice. They could be considered as general guidelines based on best available evidence for assistance in treatment decision-making. Furthermore, they serve to identify questions and targets for further research and the settings in which investigational therapy could be considered. PMID:26751386

  1. Treatment of Aggressive Prolactin-Secreting Pituitary Adenomas with Adjuvant Temozolomide Chemotherapy: A Review.

    PubMed

    Moisi, Marc; Cruz, Aurora S; Benkers, Tara; Rostad, Steven; Broyles, Frances Broyles; Yuen, Kevin; Mayberg, Marc

    2016-01-01

    Most prolactin-secreting pituitary adenomas demonstrate slow growth and are effectively managed with medical/surgical therapy. Rarely, these tumors can behave aggressively with rapid growth and invasion of local tissues, and are refractory to medical, surgical, or radio-surgical therapies. We report a case of a prolactin-secreting adenoma in a young woman, which became progressively aggressive and refractory to usual treatment modalities, but responded to treatment with the chemotherapeutic agent temozolomide. In addition, we review the literature for treatment of refractory adenomas with temozolomide. The clinical and pathologic characteristics of aggressive prolactin-secreting adenomas are reviewed, as well as their response to dopamine agonists, surgery, radiotherapy, and chemotherapy. PMID:27489751

  2. Treatment of Aggressive Prolactin-Secreting Pituitary Adenomas with Adjuvant Temozolomide Chemotherapy: A Review

    PubMed Central

    Cruz, Aurora S; Benkers, Tara; Rostad, Steven; Broyles, Frances Broyles; Yuen, Kevin; Mayberg, Marc

    2016-01-01

    Most prolactin-secreting pituitary adenomas demonstrate slow growth and are effectively managed with medical/surgical therapy. Rarely, these tumors can behave aggressively with rapid growth and invasion of local tissues, and are refractory to medical, surgical, or radio-surgical therapies. We report a case of a prolactin-secreting adenoma in a young woman, which became progressively aggressive and refractory to usual treatment modalities, but responded to treatment with the chemotherapeutic agent temozolomide. In addition, we review the literature for treatment of refractory adenomas with temozolomide. The clinical and pathologic characteristics of aggressive prolactin-secreting adenomas are reviewed, as well as their response to dopamine agonists, surgery, radiotherapy, and chemotherapy. PMID:27489751

  3. Protective effect of rPb40 as an adjuvant for chemotherapy in experimental paracoccidioidomycosis.

    PubMed

    Fernandes, V C; Martins, E M N; Boeloni, J N; Serakides, R; Goes, A M

    2012-08-01

    The conventional treatment for the most prevalent mycosis in Latin America, paracoccidioidomycosis (PCM), involves long periods of therapy that results in side effects and a high frequency of relapses. The search for a new, alternative treatment is necessary. Pb40 is an antigenic protein from P. brasiliensis fraction F0. This fraction has already been shown to have significant protective activity when used as a PCM vaccine in experimental models. The complete cDNA sequence corresponding to Pb40 was cloned into a pET-21a plasmid, expressed in E. coli with a his-tag and purified by affinity chromatography. The predicted protein sequence exhibited nearly 100% homology to a fragment of the hypothetical EF-hand domain containing protein of P. brasiliensis. Immunization with this recombinant protein was used together with chemotherapy in an attempt to improve PCM treatment. The combined drug/rPb40 treatment exhibited long-lasting control of PCM in the liver and spleen and largely preserved the tissue structures of these organs. Despite the lack of a reduction in CFUs in the group that received the combined treatment, there was a significant reduction in the size of the lesions in the lungs after 70 days of infection. At the same time, the IL-10 levels were higher in the treated mice than in the infected-only mice. Moreover, significant levels of rPb40-specific IgG antibodies were detected in the sera of immunized mice. Thus, the treatment protocol consisting of rPb40 immunization in addition to fluconazole chemotherapy showed an additive protective effect after intratracheal challenge, preventing fungal dissemination to other sites of infection and preventing relapses. These results provide new prospects for PCM immunotherapy. PMID:22391822

  4. Additional Therapy with a Mistletoe Product during Adjuvant Chemotherapy of Breast Cancer Patients Improves Quality of Life: An Open Randomized Clinical Pilot Trial.

    PubMed

    Tröger, Wilfried; Zdrale, Zdravko; Tišma, Nevena; Matijašević, Miodrag

    2014-01-01

    Background. Breast cancer patients receiving adjuvant chemotherapy often experience a loss of quality of life. Moreover chemotherapy may induce neutropenia. Patients report a better quality of life when additionally treated with mistletoe products during chemotherapy. Methods. In this prospective randomized open-label pilot study 95 patients were randomized into three groups. All patients were treated with an adjuvant chemotherapy. The primary objective of the study was quality of life, the secondary objective was neutropenia. Here we report the comparison of HxA (n = 34) versus untreated control (n = 31). Results. In the explorative analysis ten of 15 scores of the EORTC QLQ-C30 showed a better quality of life in the HxA group compared to the control group (P < 0.001 to P = 0.038 in Dunnett-T3 test). The difference was clinically relevant (difference of at least 5 points, range 5.4-12.2) in eight of the ten scores. Neutropenia occurred in 7/34 HxA patients and in 8/31 control patients (P = 0.628). Conclusions. This pilot study showed an improvement of quality of life by treating breast cancer patients with HxA additionally to CAF. Although the open design may be a limitation, the findings show the feasibility of a confirmatory study using the methods described here. PMID:24701238

  5. Therapeutic Usefulness of Postoperative Adjuvant Chemotherapy with Tegafur–Uracil (UFT) in Patients with Breast Cancer: Focus on the Results of Clinical Studies in Japan

    PubMed Central

    Noguchi, Shinzaburo

    2010-01-01

    In Japan, the history of postoperative chemotherapy for breast cancer started with 5-fluorouracil (5-FU), launched in the 1980s. Currently, oral fluoropyrimidine–based regimens indicated for the treatment of breast cancer in Japan include tegafur plus uracil (UFT); tegafur, gimeracil, and oteracil (TS-1); doxifluridine; and capecitabine. In particular, UFT represents an important option for long-term treatment because of minimal adverse events and the potential for long-term maintenance of effective plasma concentrations of 5-FU to inhibit micrometastasis after surgery. Therefore, various clinical studies of postoperative adjuvant chemotherapy with UFT have been conducted in patients with completely resected tumors. Recent studies have shown that UFT prolongs survival after tumor resection in patients with gastric cancer, colorectal cancer, and lung cancer. In patients with breast cancer, large clinical trials of UFT-based postoperative chemotherapy conducted in Japan have shown that UFT is useful for the treatment of intermediate-risk patients with no lymph node metastasis. This paper reviews the results of clinical studies of UFT conducted in Japan to assess the therapeutic usefulness of this oral 5-FU. The types of patients most likely to benefit from UFT are discussed on the basis of currently available evidence and a global consensus of treatment recommendations. The optimal timing of endocrine therapy and strategies for postoperative adjuvant chemotherapy with UFT in patients with breast cancer are also discussed. PMID:20080863

  6. Additional Therapy with a Mistletoe Product during Adjuvant Chemotherapy of Breast Cancer Patients Improves Quality of Life: An Open Randomized Clinical Pilot Trial

    PubMed Central

    Tröger, Wilfried; Ždrale, Zdravko; Tišma, Nevena; Matijašević, Miodrag

    2014-01-01

    Background. Breast cancer patients receiving adjuvant chemotherapy often experience a loss of quality of life. Moreover chemotherapy may induce neutropenia. Patients report a better quality of life when additionally treated with mistletoe products during chemotherapy. Methods. In this prospective randomized open-label pilot study 95 patients were randomized into three groups. All patients were treated with an adjuvant chemotherapy. The primary objective of the study was quality of life, the secondary objective was neutropenia. Here we report the comparison of HxA (n = 34) versus untreated control (n = 31). Results. In the explorative analysis ten of 15 scores of the EORTC QLQ-C30 showed a better quality of life in the HxA group compared to the control group (P < 0.001 to P = 0.038 in Dunnett-T3 test). The difference was clinically relevant (difference of at least 5 points, range 5.4–12.2) in eight of the ten scores. Neutropenia occurred in 7/34 HxA patients and in 8/31 control patients (P = 0.628). Conclusions. This pilot study showed an improvement of quality of life by treating breast cancer patients with HxA additionally to CAF. Although the open design may be a limitation, the findings show the feasibility of a confirmatory study using the methods described here. PMID:24701238

  7. Patterns of Care in the Administration of Neo-adjuvant Chemotherapy for Breast Cancer. A Population-Based Study.

    PubMed

    Vugts, Guusje; Maaskant-Braat, Adriana J G; Nieuwenhuijzen, Grard A P; Roumen, Rudi M H; Luiten, Ernest J T; Voogd, Adri C

    2016-05-01

    Neo-adjuvant chemotherapy (NAC) is used to facilitate radical surgery for initially irresectable or locally advanced breast cancer. The indication for NAC has been extended to clinically node negative (cN0) patients in whom adjuvant systemic therapy is foreseen. A population-based study was conducted to evaluate the increasing use of NAC, breast conserving surgery (BCS) after NAC and timing of the sentinel node biopsy (SNB). All female breast cancer patients, treated in 10 hospitals in the Eindhoven Cancer Registry area in the Netherlands between January 2003 and June 2012 were included (N = 18,427). In total, 1,402 patients (7.6%) received NAC. The administration increased from 2.5% in 2003 to 13.0% in 2011 (p < 0.001). Use of NAC increased from 0.5% to 2.3% for cT1 tumors, from 2.8% to 27.0% for cT2, from 30.6% to 70.9% for cT3, and from 40.5% to 58.1% for cT4 tumors (p < 0.001). In cN0 patients, use of NAC increased from 1.0% to 4.4% and in clinically node positive patients from 12.0% to 57.5% (p < 0.001). Downsizing of the tumor and BCS are achieved increasingly. In 2011, in three hospitals NAC was administered in <10% of patients, in five hospitals in 10-15% and in two hospitals the proportion of patients receiving NAC was >20% (p < 0.001). Of the 1,402 patients with NAC, 495 patients underwent SNB, 91.5% of whom prior to NAC. In the Netherlands up to one in eight patients receive NAC. The administration of NAC and the percentage of BCS increased over the past decade, especially in cT2 tumors. Considerable hospital variation in the administration of NAC exists. PMID:26945566

  8. Goserelin, as an ovarian protector during (neo)adjuvant breast cancer chemotherapy, prevents long term altered bone turnover

    PubMed Central

    Wilson, Caroline; Gossiel, Fatma; Leonard, Robert; Anderson, Richard A; Adamson, Douglas J A; Thomas, Geraldine; Coleman, Robert E

    2016-01-01

    Background The Ovarian Protection Trial In Premenopausal Breast Cancer Patients “OPTION” trial (NCT00427245) was a prospective, multicenter, randomised, open label study evaluating the frequency of primary ovarian insufficiency (POI) at 12 months in women randomised to 6–8 cycles of (neo)adjuvant chemotherapy (CT) +/− goserelin (G). Here we report the results of a secondary endpoint analysis of the effects of CT+/-G on markers of bone turnover. Methods Serum for bone alkaline phosphatase (BALP) and urine for N-terminal telopeptide (NTX) were collected at baseline, 6, 12, 18, 24 and 36 months. Changes in median levels of bone turnover markers were evaluated for the overall population, according to age stratification at randomisation (≤40 vs >40 years) and with exploratory analysis according to POI rates at 12 months. Results In the overall population, there was a significant increase in NTX at 6 months compared to baseline in patients treated with CT+G (40.81 vs 57.82 p=0.0074) with normalisation of levels thereafter. BALP was significantly increased compared to baseline at 6 months and 12 months in those receiving CT+G, but normalised thereafter. BALP remained significantly higher compared to baseline at 12, 24 and 36 months in patients receiving CT, resulting in a significant difference between treatment groups at 36 months (CT+G 5.845 vs CT 8.5 p=0.0006). These changes were predominantly seen in women >40 years. Women with POI at 12 months showed altered bone formation compared to baseline levels for a longer duration than women who maintained menses. Conclusion Addition of G to CT increases bone turnover during treatment with normalisation after cessation of treatment suggesting G may offer sufficient ovarian protection against CT induced POI to negate longstanding altered bone turnover associated with POI. PMID:26998426

  9. Cardiac Tolerability of Concurrent Administration of Trastuzumab and Anthracycline-Based Regimen as Adjuvant Chemotherapy for Breast Cancer

    PubMed Central

    Watanabe, Naoki; Otsuka, Shoko; Sasaki, Yoko; Shimojima, Reiko; Wani, Yoji; Uchino, Kaori

    2014-01-01

    Summary Background Retrospective analysis suggests that anthracycline-containing regimens may be superior to non-anthracycline-containing regimens in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, both trastuzumab and anthracycline have cardiotoxicity, and it remains unclear how to use trastuzumab in combination with an anthracycline to curtail their cardiotoxicity. Patients and Methods From 2010 to 2013, we administered weekly (q1w) paclitaxel (wP) followed by 75 mg/m2 epirubicin, fluorouracil, and cyclophosphamide (FEC) every third week (q3w) and concurrent q1w trastuzumab (H) to 41 patients with HER2-positive breast cancer (H+ group), and wP followed by FEC100 without trastuzumab to 57 patients who were HER2-negative (H– group). We routinely assessed the left ventricular ejection fraction (LVEF) by echocardiography, at the time of initiation, after wP, and after FEC, and compared them between these 2 groups. Results LVEF decreased from 63.2 to 60.9% (p = 0.030) in the H+ group and from 63.9 to 61.9% (p = 0.009) in the H– group. These 2 groups showed no significant difference in the reduction rate of LVEF over the period of chemotherapy (0.968 vs. 0.978: NS, p = 0.6457). There was no severe cardiotoxicity or congestive heart failure in either group. Conclusion Concurrent administration of epirubicin (q3w, 75 mg/m2) and trastuzumab showed no less cardiac tolerability in an adjuvant setting. PMID:24803887

  10. A randomized phase III trial comparing S-1 versus UFT as adjuvant chemotherapy for stage II/III rectal cancer (JFMC35-C1: ACTS-RC)

    PubMed Central

    Oki, E.; Murata, A.; Yoshida, K.; Maeda, K.; Ikejiri, K.; Munemoto, Y.; Sasaki, K.; Matsuda, C.; Kotake, M.; Suenaga, T.; Matsuda, H.; Emi, Y.; Kakeji, Y.; Baba, H.; Hamada, C.; Saji, S.; Maehara, Y.

    2016-01-01

    Backgrounds Preventing distant recurrence and achieving local control are important challenges in rectal cancer treatment, and use of adjuvant chemotherapy has been studied. However, no phase III study comparing adjuvant chemotherapy regimens for rectal cancer has demonstrated superiority of a specific regimen. We therefore conducted a phase III study to evaluate the superiority of S-1 to tegafur–uracil (UFT), a standard adjuvant chemotherapy regimen for curatively resected stage II/III rectal cancer in Japan, in the adjuvant setting for rectal cancer. Patients and methods The ACTS-RC trial was an open-label, randomized, phase III superiority trial conducted at 222 sites in Japan. Patients aged 20–80 with stage II/III rectal cancer undergoing curative surgery without preoperative therapy were randomly assigned to receive UFT (500–600 mg/day on days 1–5, followed by 2 days rest) or S-1 (80–120 mg/day on days 1–28, followed by 14 days rest) for 1 year. The primary end point was relapse-free survival (RFS), and the secondary end points were overall survival and adverse events. Results In total, 961 patients were enrolled from April 2006 to March 2009. The primary analysis was conducted in 480 assigned to receive UFT and 479 assigned to receive S-1. Five-year RFS was 61.7% [95% confidence interval (CI) 57.1% to 65.9%] for UFT and 66.4% (95% CI 61.9% to 70.5%) for S-1 [P = 0.0165, hazard ratio (HR): 0.77, 95% CI 0.63–0.96]. Five-year survival was 80.2% (95% CI 76.3% to 83.5%) for UFT and 82.0% (95% CI 78.3% to 85.2%) for S-1. The main grade 3 or higher adverse events were increased alanine aminotransferase and diarrhea (each 2.3%) in the UFT arm and anorexia, diarrhea (each 2.6%), and fatigue (2.1%) in the S-1 arm. Conclusion One-year S-1 treatment is superior to UFT with respect to RFS and has therefore become a standard adjuvant chemotherapy regimen for stage II/III rectal cancer following curative resection. PMID:27056996

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

    PubMed

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

    2002-01-01

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

  12. [Adjuvant Systemic Chemotherapy with S-1/Oxaliplatin or mFOLFOX6 after Curative Resection of Distant Metastases in Patients with Colorectal Cancer].

    PubMed

    Miyata, Ryohei; Kameyama, Noriaki; Tomita, Masato; Mitsuhashi, Hiroaki; Baba, Shigeaki; Amada, En

    2016-03-01

    This study was aimed to assess the feasibility and short-term outcomes of adjuvant systemic chemotherapy with either S-1/oxaliplatin (SOX) or mFOLFOX6 (FOLFOX)after curative resection of distant metastases from colorectal cancer. We retrospectively examined 16 patients who underwent R0 resection of colorectal metastases, including the liver (n=6), lung (n=5), lymph node (n=3), and peritoneum (n=2), followed by chemotherapy with SOX (n=7) or FOLFOX (n=9) until disease progression. The mean recurrence-free survival was 13.2 months in the SOX group and 16.9 months in the FOLFOX group. The mean overall survival was 17.9 and 22.9 months, respectively. The number of given courses were 6.5 and 11.0, respectively. Although sensory neuropathy was observed in 38% of the patients, relative dose intensity was higher than 80%. Adjuvant chemotherapy with SOX or FOLFOX was feasible and effective. Further randomized prospective trials are warranted to confirm these results. PMID:27067848

  13. A prospective phase II study of chemoradiation followed by adjuvant chemotherapy for FIGO stage I-IIIa (1988) uterine papillary serous carcinoma of the endometrium

    PubMed Central

    Jhingran, Anuja; Ramondetta, Lois M.; Bodurka, Diane C.; Slomovitz, Brian M.; Brown, Jubilee; Levy, Lawrence B.; Garcia, Michael E.; Eifel, Patricia J.; Lu, Karen H.; Burke, Thomas W.

    2015-01-01

    Objective To prospectively evaluate tumor control, survival, and toxic effects in patients with International Federation of Gynecology and Obstetrics (1988) stage I-IIIA papillary serous carcinoma of the endometrium treated with concurrent chemoradiation and adjuvant chemotherapy. Methods Thirty-two patients were enrolled from October 2001 through July 2009. Patients underwent full surgical disease staging and postoperative concurrent weekly paclitaxel (50 mg/m2) and pelvic RT to 45 Gy plus a vaginal cuff boost followed by 4 cycles of adjuvant paclitaxel (135 mg/m2). Results Thirty patients (94%) were evaluable (3 with stage IA disease, 11 IB, 3 IC, 1 IIB, and 12 IIIA). Eighteen patients (60%) received all 5 planned courses of concurrent chemotherapy, 10 (33%) received 4 courses, and 2 (7%) received 3 courses. All 30 patients received RT; 27 (90%) received the full dose, 2 received 43.2 Gy, and 1 received 39.6 Gy owing to toxic effects. Twenty-three patients (77%) completed all 4 cycles of adjuvant paclitaxel, 3 (10%) completed 3 cycles, 2 (7%) completed 2 cycles, and 2 received no adjuvant therapy. Overall survival (OS), progression-free survival (PFS), and local control rates for all patients were 93%, 87%, and 87%, respectively, at 2 years and 85%, 83%, and 87%, respectively, at 5 years. Six patients developed (20%) grade 3/4 toxcities from the treatment. Four patients (13%) had grade 3 or more severe bowel complications and two patients developed symptomatic pelvic fractures. Conclusions Treatment with concurrent paclitaxel and pelvic RT followed by 4 courses of systemic paclitaxel produced favorable results in patients with surgically staged I-III UPSC. PMID:23385150

  14. Prospective evaluation of concurrent paclitaxel and radiation therapy after adjuvant doxorubicin and cyclophosphamide chemotherapy for Stage II or III breast cancer

    SciTech Connect

    Burstein, Harold J. . E-mail: hburstein@partners.org; Bellon, Jennifer R.; Galper, Sharon; Lu, H.-M.; Kuter, Irene; Wong, Julia; Gelman, Rebecca; Bunnell, Craig A.; Parker, Leroy M.; Garber, Judy E.; Winer, Eric P.; Harris, Jay R.; Powell, Simon N.

    2006-02-01

    Purpose: To evaluate the safety and feasibility of concurrent radiation therapy and paclitaxel-based adjuvant chemotherapy, given either weekly or every 3 weeks, after adjuvant doxorubicin and cyclophosphamide (AC). Methods and Materials: After definitive breast surgery and AC chemotherapy, 40 patients with operable Stage II or III breast cancer received protocol-based treatment with concurrent paclitaxel and radiation therapy. Paclitaxel was evaluated on 2 schedules, with treatment given either weekly x 12 weeks (60 mg/m{sup 2}), or every 3 weeks x 4 cycles (135-175 mg/m{sup 2}). Radiation fields and schedules were determined by the patient's surgery and pathology. The tolerability of concurrent therapy was evaluated in cohorts of 8 patients as a phase I study. Results: Weekly paclitaxel treatment at 60 mg/m{sup 2} per week with concurrent radiation led to dose-limiting toxicity in 4 of 16 patients (25%), including 3 who developed pneumonitis (either Grade 2 [1 patient] or Grade 3 [2 patients]) requiring steroids. Efforts to eliminate this toxicity in combination with weekly paclitaxel through treatment scheduling and CT-based radiotherapy simulation were not successful. By contrast, dose-limiting toxicity was not encountered among patients receiving concurrent radiation with paclitaxel given every 3 weeks at 135-175 mg/m{sup 2}. However, Grade 2 radiation pneumonitis not requiring steroid therapy was seen in 2 of 24 patients (8%) treated in such a fashion. Excessive radiation dermatitis was not observed with either paclitaxel schedule. Conclusions: Concurrent treatment with weekly paclitaxel and radiation therapy is not feasible after adjuvant AC chemotherapy for early-stage breast cancer. Concurrent treatment using a less frequent paclitaxel dosing schedule may be possible, but caution is warranted in light of the apparent possibility of pulmonary injury.

  15. A clinical prognostic scoring system for resectable gastric cancer to predict survival and benefit from paclitaxel- or oxaliplatin-based adjuvant chemotherapy

    PubMed Central

    Qian, Jing; Qian, Yingying; Wang, Jian; Gu, Bing; Pei, Dong; He, Shaohua; Zhu, Fang; Røe, Oluf Dimitri; Xu, Jin; Liu, Lianke; Gu, Yanhong; Guo, Renhua; Yin, Yongmei; Shu, Yongqian; Chen, Xiaofeng

    2016-01-01

    Background Gastrectomy with D2 lymphadenectomy is a standard procedure of curative resection for gastric cancer (GC). The aim of this study was to develop a simple and reliable prognostic scoring system for GC treated with D2 gastrectomy combined with adjuvant chemotherapy. Methods A prognostic scoring system was established based on clinical and laboratory data from 579 patients with localized GC without distant metastasis treated with D2 gastrectomy and adjuvant chemotherapy. Results From the multivariate model for overall survival (OS), five factors were selected for the scoring system: ≥50% metastatic lymph node rate, positive lymphovascular invasion, pathologic TNM Stage II or III, ≥5 ng/mL preoperative carcinoembryonic antigen level, and <110 g/L preoperative hemoglobin. Two models were derived using different methods. Model A identified low- and high-risk patients for OS (P<0.001), while Model B differentiated low-, intermediate-, and high-risk patients for OS (P<0.001). Stage III patients in the low-risk group had higher survival probabilities than Stage II patients. Both Model A (area under the curve [AUC]: 0.74, 95% confidence interval [CI]: 0.69–0.78) and Model B (AUC: 0.79, 95% CI: 0.72–0.83) were better predictors compared with the pathologic TNM classification (AUC: 0.62, 95% CI: 0.59–0.71, P<0.001). Adjuvant paclitaxel- or oxaliplatin-based or triple chemotherapy showed significantly better outcomes in patients classified as high risk, but not in those with low and intermediate risk. Conclusion A clinical three-tier prognostic risk scoring system was established to predict OS of GC treated with D2 gastrectomy and adjuvant chemotherapy. The potential advantage of this scoring system is that it can identify high-risk patients in Stage II or III who may benefit from paclitaxel- or oxaliplatin-based regimens. Prospective studies are needed to confirm these results before they are applied clinically. PMID:26966350

  16. Adjuvant Chemotherapy With or Without Pelvic Radiotherapy After Simultaneous Surgical Resection of Rectal Cancer With Liver Metastases: Analysis of Prognosis and Patterns of Recurrence

    SciTech Connect

    An, Ho Jung; Yu, Chang Sik; Yun, Sung-Cheol; Kang, Byung Woog; Hong, Yong Sang; Lee, Jae-Lyun; Ryu, Min-Hee; Chang, Heung Moon; Park, Jin Hong; Kim, Jong Hoon; Kang, Yoon-Koo; Kim, Jin Cheon; Kim, Tae Won

    2012-09-01

    Purpose: To investigate the outcomes of adjuvant chemotherapy (CT) or chemoradiotherapy (CRT) after simultaneous surgical resection in rectal cancer patients with liver metastases (LM). Materials and Methods: One hundred and eight patients receiving total mesorectal excision for rectal cancer and surgical resection for LM were reviewed. Forty-eight patients received adjuvant CRT, and 60 were administered CT alone. Recurrence patterns and prognosis were analyzed. Disease-free survival (DFS) and overall survival (OS) rates were compared between the CRT and CT groups. The inverse probability of the treatment-weighted (IPTW) method based on the propensity score was used to adjust for selection bias between the two groups. Results: At a median follow-up period of 47.7 months, 77 (71.3%) patients had developed recurrences. The majority of recurrences (68.8%) occurred in distant organs. By contrast, the local recurrence rate was only 4.7%. Median DFS and OS were not significantly different between the CRT and CT groups. After applying the IPTW method, we observed no significant differences in terms of DFS (hazard ratio [HR], 1.347; 95% confidence interval [CI], 0.759-2.392; p = 0.309) and OS (HR, 1.413; CI, 0.752-2.653; p = 0.282). Multivariate analyses showed that unilobar distribution of LM and normal preoperative carcinoembryonic antigen level (<6 mg/mL) were significantly associated with longer DFS and OS. Conclusions: The local recurrence rate after simultaneous resection of rectal cancer with LM was relatively low. DFS and OS rates were not different between the adjuvant CRT and CT groups. Adjuvant CRT may have a limited role in this setting. Further prospective randomized studies are required to evaluate optimal adjuvant treatment in these patients.

  17. Adjuvant chemotherapy for early female breast cancer: a systematic review of the evidence for the 2014 Cancer Care Ontario systemic therapy guideline

    PubMed Central

    Gandhi, S.; Fletcher, G.G.; Eisen, A.; Mates, M.; Freedman, O.C.; Dent, S.F.; Trudeau, M.E.

    2015-01-01

    Background The Program in Evidence-Based Care (pebc) of Cancer Care Ontario recently created an evidence-based consensus guideline on the systemic treatment of early breast cancer. The evidence for the guideline was compiled using a systematic review to answer the question “What is the optimal systemic therapy for patients with early-stage, operable breast cancer, when patient and disease factors are considered?” The question was addressed in three parts: cytotoxic chemotherapy, endocrine treatment, and human epidermal growth factor receptor 2 (her2)–directed therapy. Methods For the systematic review, the medline and embase databases were searched for the period January 2008 to May 2014. The Standards and Guidelines Evidence directory of cancer guidelines and the Web sites of major oncology guideline organizations were also searched. The basic search terms were “breast cancer” and “systemic therapy” (chemotherapy, endocrine therapy, targeted agents, ovarian suppression), and results were limited to randomized controlled trials (rcts), guidelines, systematic reviews, and meta-analyses. Results Several hundred documents that met the inclusion criteria were retrieved. The Early Breast Cancer Trialists’ Collaborative Group meta-analyses encompassed many of the rcts found. Several additional studies that met the inclusion criteria were retained, as were other guidelines and systematic reviews. Chemotherapy was reviewed mainly in three classes: anti-metabolite–based regimens (for example, cyclophosphamide–methotrexate–5-fluorouracil), anthracyclines, and taxane-based regimens. In general, single-agent chemotherapy is not recommended for the adjuvant treatment of breast cancer in any patient population. Anthracycline–taxane-based polychemotherapy regimens are, overall, considered superior to earlier-generation regimens and have the most significant impact on patient survival outcomes. Regimens with varying anthracycline and taxane doses and

  18. Cost-effectiveness of adjuvant chemotherapy with uracil–tegafur for curatively resected stage III rectal cancer

    PubMed Central

    Hisashige, A; Yoshida, S; Kodaira, S

    2008-01-01

    Recently, the National Surgical Adjuvant Study of Colorectal Cancer in Japan, a randomised controlled trial of oral uracil–tegafur (UFT) adjuvant therapy for stage III rectal cancer, showed remarkable survival gains, compared with surgery alone. To evaluate value for money of adjuvant UFT therapy, cost-effective analysis was carried out. Cost-effectiveness analysis of adjuvant UFT therapy was carried out from a payer's perspective, compared with surgery alone. Overall survival and relapse-free survival were estimated by Kaplan–Meier method, up to 5.6 years from randomisation. Costs were estimated from trial data during observation. Quality-adjusted life-years (QALYs) were calculated using utility score from literature. Beyond observation period, they were simulated by the Boag model combined with the competing risk model. For 5.6-year observation, 10-year follow-up and over lifetime, adjuvant UFT therapy gained 0.50, 0.96 and 2.28 QALYs, and reduced costs by $2457, $1771 and $1843 per person compared with surgery alone, respectively (3% discount rate for both effect and costs). Cost-effectiveness acceptability and net monetary benefit analyses showed the robustness of these results. Economic evaluation of adjuvant UFT therapy showed that this therapy is cost saving and can be considered as a cost-effective treatment universally accepted for wide use in Japan. PMID:18797469

  19. Loss of ataxia-telangiectasia-mutated protein expression correlates with poor prognosis but benefits from anthracycline-containing adjuvant chemotherapy in breast cancer.

    PubMed

    Suh, Koung Jin; Ryu, Han Suk; Lee, Kyung-Hun; Kim, Hyojin; Min, Ahrum; Kim, Tae-Yong; Yang, Yaewon; Moon, Hyeong-Gon; Han, Sae-Won; Oh, Do-Youn; Han, Wonshik; Park, In Ae; Noh, Dong-Young; Im, Seock-Ah

    2016-07-01

    We investigated the correlation of ataxia-telangiectasia-mutated (ATM) protein expression with clinicopathological features and prognosis in patients with breast cancer. ATM expression was determined by immunohistochemistry in 420 surgically resected breast tumors. ATM loss was observed in 126/407 evaluable cases (31.0 %), and was significantly associated with larger tumor size, lymph node metastasis, higher tumor grade, and ER- and/or PR-negative status. ATM loss was also associated with significantly lower disease-free survival rates than those in patients with intact ATM (5-year disease-free survival rate 81.2 vs. 90.7 %, p = 0.015). In multivariate analysis, ATM loss combined with abnormal p53 expression was an independent predictor of shorter disease-free survival [hazard ratio (HR) 3.48; 95 % confidence interval (CI), 1.48-8.17, p = 0.004]. A tendency towards a poorer prognosis was observed for tumoral ATM loss alone, although statistical significance was not reached (HR 1.74; 95 % CI 0.95-3.20; p = 0.075). In subgroup analysis, ATM loss was associated with shorter disease-free survival in patients who did not receive adjuvant anthracycline chemotherapy (5-year disease-free survival rate 92.7 % in intact ATM group vs. 68.1 % in ATM loss group, p = 0.002), but this poor prognosis was overcome in patients who did (5-year disease-free survival rate 89.8 vs. 84.4 %, p = 0.243), suggesting more benefit from anthracycline-based chemotherapy. Tumors with loss of ATM expression have a poor prognosis and their prognoses are dependent on the use of adjuvant anthracycline. ATM loss might be a practical tool for predicting benefits from anthracycline-based adjuvant therapy. PMID:27329169

  20. MGMT Promoter Methylation Is Prognostic but Not Predictive for Outcome to Adjuvant PCV Chemotherapy in Anaplastic Oligodendroglial Tumors: A Report From EORTC Brain Tumor Group Study 26951

    PubMed Central

    van den Bent, Martin J.; Dubbink, Hendrikus J.; Sanson, Marc; van der Lee-Haarloo, Cathleen R.; Hegi, Monika; Jeuken, Judith W.M.; Ibdaih, Ahmed; Brandes, Alba A.; Taphoorn, Martin J.B.; Frenay, Marc; Lacombe, Denis; Gorlia, Thierry; Dinjens, Winand N.M.; Kros, Johan M.

    2009-01-01

    Purpose O6-methylguanine-methyltransferase (MGMT) promoter methylation has been shown to predict survival of patients with glioblastomas if temozolomide is added to radiotherapy (RT). It is unknown if MGMT promoter methylation is also predictive to outcome to RT followed by adjuvant procarbazine, lomustine, and vincristine (PCV) chemotherapy in patients with anaplastic oligodendroglial tumors (AOT). Patients and Methods In the European Organisation for the Research and Treatment of Cancer study 26951, 368 patients with AOT were randomly assigned to either RT alone or to RT followed by adjuvant PCV. From 165 patients of this study, formalin-fixed, paraffin-embedded tumor tissue was available for MGMT promoter methylation analysis. This was investigated with methylation specific multiplex ligation-dependent probe amplification. Results In 152 cases, an MGMT result was obtained, in 121 (80%) cases MGMT promoter methylation was observed. Methylation strongly correlated with combined loss of chromosome 1p and 19q loss (P = .00043). In multivariate analysis, MGMT promoter methylation, 1p/19q codeletion, tumor necrosis, and extent of resection were independent prognostic factors. The prognostic significance of MGMT promoter methylation was equally strong in the RT arm and the RT/PCV arm for both progression-free survival and overall survival. In tumors diagnosed at central pathology review as glioblastoma, no prognostic effect of MGMT promoter methylation was observed. Conclusion In this study, on patients with AOT MGMT promoter methylation was of prognostic significance and did not have predictive significance for outcome to adjuvant PCV chemotherapy. The biologic effect of MGMT promoter methylation or pathogenetic features associated with MGMT promoter methylation may be different for AOT compared with glioblastoma. PMID:19901104

  1. Impact of resistance and aerobic exercise on sarcopenia and dynapenia in breast cancer patients receiving adjuvant chemotherapy: a multicenter randomized controlled trial.

    PubMed

    Adams, Scott C; Segal, Roanne J; McKenzie, Donald C; Vallerand, James R; Morielli, Andria R; Mackey, John R; Gelmon, Karen; Friedenreich, Christine M; Reid, Robert D; Courneya, Kerry S

    2016-08-01

    The purpose of this study was to conduct an exploratory analysis of the START examining the effects of resistance exercise training (RET) and aerobic exercise training (AET) on sarcopenia, dynapenia, and associated quality of life (QoL) changes in breast cancer (BC) patients receiving adjuvant chemotherapy. Participants were randomized to usual care (UC) (n = 70), AET (n = 64), or RET (n = 66) for the duration of chemotherapy. Measures of sarcopenia [skeletal muscle index (SMI)] and dynapenia [upper extremity (UE) and lower extremity (LE) muscle dysfunction (MD)] were normalized relative to age-/sex-based clinical cut-points. QoL was assessed by the Functional Assessment of Cancer Therapy-Anemia (FACT-An) scales. At baseline, 25.5 % of BC patients were sarcopenic and 54.5 % were dynapenic with both conditions associated with poorer QoL. ANCOVAs showed significant differences favoring RET over UC for SMI (0.32 kg/m(2); p = 0.017), UE-MD (0.12 kg/kg; p < 0.001), and LE-MD (0.27 kg/kg; p < 0.001). Chi-square analyses revealed significant effects of RET, compared to UC/AET combined, on reversing sarcopenia (p = 0.039) and dynapenia (p = 0.019). The reversal of sarcopenia was associated with clinically relevant improvements in the FACT-An (11.7 points [95 % confidence interval (CI) -4.2 to 27.6]), the Trial Outcome Index-Anemia (10.0 points [95 % CI -4.0 to 24.1]), and fatigue (5.3 points [95 % CI -1.5 to 12.1]). Early-stage BC patients initiating adjuvant chemotherapy have higher than expected rates of sarcopenia and dynapenia which are associated with poorer QoL. RET during adjuvant chemotherapy resulted in the reversal of both sarcopenia and dynapenia; however, only the reversal of sarcopenia was associated with clinically meaningful improvements in QoL. PMID:27394134

  2. Adjuvant treatment

    PubMed Central

    Sultana, Asma; Neoptolemos, John

    2006-01-01

    Exocrine pancreatic cancer (pancreatic ductal adenocarcinoma) is one of the leading causes of cancer deaths in the western world, accounting for 5% of all cancer-related deaths. Only a small percentage of patients with pancreatic cancer are able to undergo potentially curative resection, even in specialized centres, and prognosis remains poor after successful surgery. Over the last few years efforts have been directed towards the development of adjuvant therapies in attempts to improve outcome. The main trials of adjuvant chemotherapy, chemoradiotherapy and chemoradiotherapy with follow-on chemotherapy are described in this paper, followed by the results of the ESPAC-1 trial and the status of ESPAC-2 and -3 trials. PMID:18333088

  3. A Phase II Clinical Trial of Concurrent Helical Tomotherapy plus Cetuximab Followed by Adjuvant Chemotherapy with Cisplatin and Docetaxel for Locally Advanced Nasopharyngeal Carcinoma

    PubMed Central

    Zhang, Xinxin; Du, Lei; Zhao, Feifang; Wang, Qiuju; Yang, Shiming; Ma, Lin

    2016-01-01

    Purpose: The present clinical trial was designed to evaluate the efficacy and safety of concurrent helical tomotherapy (HT) with cetuximab followed by adjuvant chemotherapy with docetaxel and cisplatin (TP) in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma. Materials and Methods: This phase II clinical trial included 43 patients with Stage III/IV LANC (33 Stage III and 10 Stage IV). The treatment consisted of concurrent HT with cetuximab (400 mg/m2 loading dose and weekly 250mg/m2), followed by four cycles of chemotherapy [docetaxel (70 mg/m2 on Day 1) and cisplatin (40 mg/m2 on Days 1 and 2 every 3 weeks). Side effects were evaluated with CTCAE criteria (Common Terminology Criteria for Adverse Events 3.0). Results: The median follow-up duration was 48.0 months [95% confidence interval (CI) 41.7-58.0 months], the 2-year locoregional failure-free rate (LFFR), progression-free survival (PFS), distant failure-free rate (DFFR) and overall survival (OS) were 95.2%, 79.1%, 88.1% and 93.0% respectively; the 3-year LFFR, DFFR, PFS and OS were 92.7%, 85.6%, 72.0% and 85.7% respectively. The most common grade 3 toxicities were oropharyngeal mucositis (81.4%) and RT-related dermatitis (7.0%). No patients had more than grade 3 radiation related toxicities and no patients required nasogastric feeding. One patient experienced grade 3 osteonecrosis at 18 months after treatment. Conclusions: Concurrent HT with cetuximab followed by adjuvant chemotherapy with TP is an effective strategy for the treatment of LANC with encouraging survival rates and minimal side effects. PMID:27019628

  4. Randomized Trial of Postoperative Adjuvant Therapy in Stage II and III Rectal Cancer to Define the Optimal Sequence of Chemotherapy and Radiotherapy: 10-Year Follow-Up

    SciTech Connect

    Kim, Tae-Won; Lee, Je-Hwan; Lee, Jung-Hee; Ahn, Jin-Hee; Kang, Yoon-Koo; Lee, Kyoo-Hyung; Yu, Chang-Sik; Kim, Jong-Hoon; Ahn, Seung-Do; Kim, Woo-Kun; Kim, Jin-Cheon; Lee, Jung-Shin

    2011-11-15

    Purpose: To determine the optimal sequence of postoperative adjuvant chemotherapy and radiotherapy in patients with Stage II or III rectal cancer. Methods and Materials: A total of 308 patients were randomized to early (n = 155) or late (n = 153) radiotherapy (RT). Treatment included eight cycles of chemotherapy, consisting of fluorouracil 375 mg/m{sup 2}/day and leucovorin 20 mg/m{sup 2}/day, at 4-week intervals, and pelvic radiotherapy of 45 Gy in 25 fractions. Radiotherapy started on Day 1 of the first chemotherapy cycle in the early RT arm and on Day 1 of the third chemotherapy cycle in the late RT arm. Results: At a median follow-up of 121 months for surviving patients, disease-free survival (DFS) at 10 years was not statistically significantly different between the early and late RT arms (71% vs. 63%; p = 0.162). A total of 36 patients (26.7%) in the early RT arm and 49 (35.3%) in the late RT arm experienced recurrence (p = 0.151). Overall survival did not differ significantly between the two treatment groups. However, in patients who underwent abdominoperineal resection, the DFS rate at 10 years was significantly greater in the early RT arm than in the late RT arm (63% vs. 40%; p = 0.043). Conclusions: After the long-term follow-up duration, this study failed to show a statistically significant DFS advantage for early radiotherapy with concurrent chemotherapy after resection of Stage II and III rectal cancer. Our results, however, suggest that if neoadjuvant chemoradiation is not given before surgery, then early postoperative chemoradiation should be considered for patients requiring an abdominoperineal resection.

  5. Changes over time in the impact of gene-expression profiles on the administration of adjuvant chemotherapy in estrogen receptor positive early stage breast cancer patients: A nationwide study.

    PubMed

    Kuijer, A; Drukker, C A; Elias, S G; Smorenburg, C H; Th Rutgers, E J; Siesling, S; van Dalen, Th

    2016-08-15

    Ten years ago gene-expression profiles were introduced to aid adjuvant chemotherapy decision making in breast cancer. Since then subsequent national guidelines gradually expanded the indication area for adjuvant chemotherapy. In this nation-wide study the evolution of the proportion of patients with estrogen-receptor positive (ER+) tumors receiving adjuvant chemotherapy in relation to gene-expression profile use in patient groups that became newly eligible for chemotherapy according to national guideline changes over time is assessed. Data on all surgically treated early breast cancer patients diagnosed between 2004-2006 and 2012-2014 were obtained from the Netherlands Cancer Registry. ER+/Her2- patients with tumor-characteristics making them eligible for gene-expression testing in both cohorts and a discordant chemotherapy recommendation over time (2004 guideline not recommending and 2012 guideline recommending chemotherapy) were identified. We identified 3,864 patients eligible for gene-expression profile use during both periods. Gene-expression profiles were deployed in 5% and 35% of the patients in the respective periods. In both periods the majority of patients was assigned to a low genomic risk-profile (67% and 69%, respectively) and high adherence rates to the test result were observed (86% and 91%, respectively). Without deploying a gene-expression profile 8% and 52% (p <0.001) of the respective cohorts received chemotherapy while 21% and 28% of these patients received chemotherapy when a gene-expression profile was used (p 0.191). In conclusion, in ER+/Her2- early stage breast cancer patients gene-expression profile use was associated with a consistent proportion of patients receiving chemotherapy despite an adjusted guideline-based recommendation to administer chemotherapy. PMID:27062369

  6. The Benefit of Adjuvant Chemotherapy in Elderly Patients with Stage III Colorectal Cancer is Independent of Age and Comorbidity

    PubMed Central

    Wildes, Tanya M.; Kallogjeri, Dorina; Powers, Brian; Vlahiotis, Anna; Mutch, Matthew; Spitznagel, Edward L.; Tan, Benjamin; Piccirillo, Jay F.

    2010-01-01

    Objectives To determine the combined effect of age and comorbidity on receipt of chemotherapy and its impact on survival in elderly patients with stage III colorectal cancer (CRC). Materials and methods All patients over age 65 with Stage III CRC diagnosed 1996–2006 were identified from the Barnes-Jewish Hospital Oncology Data Services registry. An age/comorbidity staging system was created using the ACE-27 comorbidity index and data from both Stage II and III CRC. The staging system was then applied to patients with Stage III CRC. Odds of receiving chemotherapy were calculated, and survival analyses determined the impact of chemotherapy on overall survival in each age/comorbidity stage. Results 435 patients with Stage III CRC were evaluated [median age 75 years (range 65–99)]. Advancing age/comorbidity stage (Alpha, Beta, Gamma) was associated with decreasing odds of receiving chemotherapy for Stage III CRC [Odds Ratio 0.83 (95% CI, 0.51–1.35) for Beta and 0.14 (95% CI, 0.08–0.24) for Gamma, compared to Alpha]. Chemotherapy was associated with lower risk of death in each of the age/comorbidity stages, compared to those who underwent surgery only. The hazard ratio for death in patients who did not receive chemotherapy, relative to those who did, within each age/comorbidity stage was 1.8 [95%CI 1.06–3.06] for Alpha, 2.24 [95%CI 1.38–3.63] for Beta and 2.10 [95% CI 1.23–3.57] for Gamma. Conclusion While stage III CRC patients with increasing age and comorbidity are less likely to receive chemotherapy, receipt of chemotherapy is associated with a lower risk of death. PMID:21113435

  7. Feasibility Of Administering Adjuvant Chemotherapy Of Pemetrexed Followed By Pemetrexed/oxaliplatin Immediately Post-VATS In Patients With Completely Resected NSCLC

    PubMed Central

    He, Jianxing; Shao, Wenlong; Li, Shuben; Chen, Manyin; Chen, Hanzhang; Liu, Jun; Wang, Wei; Qiu, Yuan; Wang, Daoyuan

    2009-01-01

    Non-small cell lung cancer (NSCLC) accounts for the largest number of cancer deaths annually, worldwide. It seems reasonable to test a less toxic regimen also in early stages after complete (R0) resection of the tumor, where reduced toxicities might improve the feasibility of drug delivery, compliance and the convenience of treatment for the patient and hence perhaps improve survival. The main purpose of this phase II trial is to evaluate the clinical feasibility-in terms of patients without dose limiting toxicities or premature treatment withdrawal or death-of administering adjuvant chemotherapy of pemetrexed followed by pemetrexed/oxaliplatin immediately post-VATS (video-assisted thoracic surgery) in patients with completely resected NSCLC. PMID:22263005

  8. Trial on Refinement of Early stage non-small cell lung cancer. Adjuvant chemotherapy with pemetrexed and cisplatin versus vinorelbine and cisplatin: The TREAT protocol

    PubMed Central

    Kreuter, Michael; Vansteenkiste, Johan; Griesinger, Frank; Hoffmann, Hans; Dienemann, Hendrik; De Leyn, Paul; Thomas, Michael

    2007-01-01

    Background Adjuvant chemotherapy has been proven to be beneficial for patients with early stage non-small cell lung cancer. However, toxicity and insufficient dose delivery have been critical issues with the chemotherapy used. Doublet regimens with pemetrexed, a multi-target folate inhibitor, and platin show clear activity in non-small cell lung cancer and are well tolerated with low toxicity rates and excellent delivery. Methods/Design In this prospective, multi-center, open label randomized phase II study, patients with pathologically confirmed non-small cell lung cancer, stage IB, IIA, IIB, T3N1 will be randomized after complete tumor resection either to 4 cycles of the standard adjuvant vinorelbine and cisplatin regimen from the published phase III data, or to 4 cycles of pemetrexed 500 mg/m2 d1 and cisplatin 75 mg/m2 d1, q 3 weeks. Primary objective is to compare the clinical feasibility of these cisplatin doublets defined as non-occurrence of grade 4 neutropenia and/or thrombocytopenia > 7 days or bleeding, grade 3/4 febrile neutropenia and/or infection, grade 3/4 non-hematological toxicity, non-acceptance leading to premature withdrawal and no cancer or therapy related death. Secondary parameters are efficacy (time to relapse, overall survival) and drug delivery. Parameters of safety are hematologic and non-hematologic toxicity of both arms. Discussion The TREAT trial was designed to evaluate the clinical feasibility, i.e. rate of patients without dose limiting toxicities or premature treatment withdrawal or death of the combination of cisplatin and pemetrexed as well as the published phase III regimen of cisplatin and vinorelbine. Hypothesis of the study is that reduced toxicities might improve the feasibility of drug delivery, compliance and the convenience of treatment for the patient and perhaps survival. Trial Registration Clinicaltrials.gov NCT00349089 PMID:17488518

  9. A seven-gene signature can predict distant recurrence in patients with triple-negative breast cancers who receive adjuvant chemotherapy following surgery.

    PubMed

    Park, Yeon Hee; Jung, Hae Hyun; Do, In-Gu; Cho, Eun Yoon; Sohn, Insuk; Jung, Sin-Ho; Kil, Won Ho; Kim, Seok Won; Lee, Jeong Eon; Nam, Seok Jin; Ahn, Jin Seok; Im, Young-Hyuck

    2015-04-15

    The aim of this study was to investigate candidate genes that might function as biomarkers to differentiate triple negative breast cancers (TNBCs) among patients, who received adjuvant chemotherapy after curative surgery. We tested whether the results of a NanoString expression assay that targeted 250 prospectively selected genes and used mRNA extracted from formalin-fixed, paraffin-embedded would predict distant recurrence in patients with TNBC. The levels of expression of seven genes were used in a prospectively defined algorithm to allocate each patient to a risk group (low or high). NanoString expression profiles were obtained for 203 tumor tissue blocks. Increased expressions of the five genes (SMAD2, HRAS, KRT6A, TP63 and ETV6) and decreased expression of the two genes (NFKB1 and MDM4) were associated favorable prognosis and were validated with cross-validation. The Kaplan-Meier estimates of the rates of distant recurrence at 10 years in the low- and high-risk groups according to gene expression signature were 62% [95% confidence interval (CI), 48.6-78.9%] and 85% (95% CI, 79.2-90.7%), respectively. When adjusting for TNM stage, the distant recurrence-free survival (DRFS)s in the low-risk group was significantly longer than that in the high-risk group (p <0.001) for early stage (I and II) and advanced stage (III) tumors. In a multivariate Cox regression model, the gene expression signature provided significant predictive power jointly with the TNM staging system. A seven-gene signature could be used as a prognostic model to predict DRFS in patients with TNBC who received curative surgery followed by adjuvant chemotherapy. PMID:25537444

  10. Long-term quality of life after intensified multi-modality treatment of oral cancer including intra-arterial induction chemotherapy and adjuvant chemoradiation

    PubMed Central

    Kovács, Adorján F.; Stefenelli, Ulrich; Thorn, Gerrit

    2015-01-01

    Background: Quality of life (QoL) studies are well established when accompanying trials in head and neck cancer, but studies on long-term survivors are rare. Aims: The aim was to evaluate long-term follow-up patients treated with an intensified multi-modality therapy. Setting and Design: Cross-sectional study, tertiary care center. Patients and Methods: A total of 135 oral/oropharyngeal cancer survivors having been treated with an effective four modality treatment (intra-arterial induction chemotherapy, radical surgery, adjuvant radiation, concurrent systemic chemotherapy) filled European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and HN35 questionnaires. Mean distance to treatment was 6.1 (1.3–16.6) years. Results were compared with a reference patient population (EORTC reference manual). In-study group comparison was also carried out. Statistical Analysis: One-sample t-test, Mann–Whitney-test, Kruskal–Wallis analysis. Results: QoL scores of both populations were well comparable. Global health status, cognitive and social functioning, fatigue, social eating, status of teeth, mouth opening and dryness, and sticky saliva were significantly worse in the study population; pain and need for pain killers, cough, need for nutritional support, problems with weight loss and gain were judged to be significantly less. Patients 1-year posttreatment had generally worse scores as compared to patients with two or more years distance to treatment. Complex reconstructive measures and adjuvant (chemo) radiation were main reasons for significant impairment of QoL. Conclusion Subjective disease status of patients following a maximized multi-modality treatment showed an expectable high degree of limitations, but was generally comparable to a reference group treated less intensively, suggesting that the administration of an intensified multi-modality treatment is feasible in terms of QoL/effectivity ratio. PMID:26389030

  11. Adjuvant chemotherapy for ypT0N0M0 rectal cancer following chemoradiotherapy and total mesorectal excision.

    PubMed

    Kainthla, Radhika; Huerta, Sergio

    2016-10-01

    The management of adenocarcinoma of the rectum is a dynamic field in oncology. The multidisciplinary approach to the management of this disease continues to evolve in each segment of its trimodality treatment. New scheduling regimens and radiosensitizing agents continue to emerge. Although total mesorectal excision continues to be the operation of choice for rectal cancers, what is done before and after surgery continues to evolve to maximize an ideal oncologic outcome with minimal morbidity. The achievement of a pathological complete response [pCR (i.e. ypT0N0)] in a fraction of patients undergoing neoadjuvant chemoradiation poses an interesting management dilemma. The cohort of patients who can achieve a pCR have superior oncologic outcomes compared to nonresponders. The present review addresses the need for adjuvant therapy in patients with a pCR. We discuss the evolution of the role of adjuvant therapy in patients with rectal cancer and the studies addressing the elimination of this strategy in all patients with rectal cancer with a goal of determining the current evidence that might result in the omission of adjuvant therapy for patients with ypT0N0 rectal cancer after chemoradiation and total mesorectal excision. PMID:27387144

  12. Prognostic Effects of Adjuvant Chemotherapy-Induced Amenorrhea and Subsequent Resumption of Menstruation for Premenopausal Breast Cancer Patients.

    PubMed

    Jeon, Se Jeong; Lee, Jae Il; Jeon, Myung Jae; Lee, Maria

    2016-04-01

    Chemotherapy-induced amenorrhea (CIA) is a side effect that occurs in patients with breast cancer (BC) as a result of chemotherapy. These patients require special treatments to avoid infertility and menopause. However, the factors controlling CIA, resumption of menstruation (RM), and persistence of menstruation after chemotherapy are unknown. The long-term prognosis for premenopausal patients with BC and the prognostic factors associated with CIA and RM are subject to debate. We performed a retrospective study by reviewing the medical records of 249 patients with BC (stage I to stage III) who were treated with cytotoxic chemotherapy. The median patient age was 43 (range, 26-55 years) and the median duration of follow-up was 64 months (range, 28-100 months). The medical records indicated that 219 patients (88.0%) scored as positive for the hormone receptor (HR); the majority of these patients completed chemotherapy and then received additional therapy of tamoxifen. Our analyses revealed that 88.0% (n = 219) of patients experienced CIA, and the percentage of RM during follow-up was 48.6% (n = 121). A total of 30 patients (12.0%) did not experience CIA. Disease-free survival (DFS) was affected by several factors, including tumour size ≥2 cm, node positivity, HR negative status, and body mass index ≥23 kg/m. Multivariate analysis indicated that tumour size ≥2 cm remained as a significant factor for DFS (hazard ratio = 3.3, P = 0.034). In summary, this study finds that the majority of premenopausal patients with BC (stage I to stage III) who receive chemotherapy experience CIA and subsequent RM. Although tumour size ≥2 cm is negatively associated with DFS, RM after CIA is not associated with poor prognosis. PMID:27057900

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

    PubMed Central

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

    2015-01-01

    Background Methylation levels of long interspersed nucleotide elements (LINE-1) are representative of genome-wide methylation status and crucial in maintaining genomic stability and expression. Their prognostic impact on colon cancer patients receiving adjuvant chemotherapy has not been well established. We evaluated the association between LINE-1 methylation status and clinicopathologic features and postoperative oncological outcomes in stage III colon cancer patients. Materials and Methods 129 UICC stage III colon cancer patients who had received radical resection and FOLFOX adjuvant chemotherapy were enrolled. Global methylation was estimated by analyzing tumor LINE-1 methylation status using bisulfite-polymerase chain reaction (PCR) and pyrosequencing assay. Demographics, clinicopathological data, and postoperative outcomes were recorded by trained abstractors. Outcome measurements included postoperative recurrence and disease-free survival. Univariate, multivariate, and survival analyses were conducted to identify prognostic factors of oncological outcomes. Results The LINE-1 methylation of all 129 patients was measured on a 0–100 scale (mean 63.3; median 63.7, standard deviation 7.1), LINE-1 hypomethylation was more common in patients aged 65 years and above (61.7%±7.6% vs. 64.6±6.4, p=0.019) and those with post-therapeutic recurrence (61.7±7.4 vs 64.3±6.7, p=0.041). Considering risk adjustment, LINE-1 hypomethylation was found to be an independent risk factor of post-therapeutic recurrence (Adjusted OR=14.1, p=0.012). Kaplan-Meier analysis indicated that patients in the low methylation group had shorter period of disease free survival (p=0.01). In a stratified analysis that included 48 patients with post-therapeutic recurrence, it was found that those who experienced shorter period of disease free survival (≦6 months) appeared to have lower LINE-1 methylation levels than patients who reported of recurrence after 6 months (56.68±15.75 vs. 63.55±7

  14. Sprouty2 protein in prediction of post-treatment ascites in epithelial ovarian cancer treated with adjuvant carbotaxol chemotherapy

    PubMed Central

    Masoumi-Moghaddam, Samar; Amini, Afshin; Wei, Ai-Qun; Robertson, Gregory; Morris, David L

    2015-01-01

    Ascites development and resistance to chemotherapy with carbotaxol are common clinical problems in epithelial ovarian cancer, partly due to the activation of MAPK/ERK signaling. Sprouty proteins are negative modulators of MAPK/ERK pathway, but their role in predicting resistance to carbotaxol chemotherapy and ascites development is unknown. In this study, we evaluated the expression of Sprouty protein isoforms by immunohistochemistry. The associations between the Sprouty expression and the clinicopathological features, including chemoresistance and the presence of ascites, were then explored. We found that the decreased expression of Spry2 was correlated with the post-treatment development of ascites and represented an independent predictor of this condition in carbotaxol-treated patients. However, no association was observed between the Sprouty expression and chemoresistance. In conclusion, our results suggest that Spry2 may be useful for patient follow-up and monitoring as it predicts the development of ascites in epithelial ovarian cancer cases treated with carbotaxol. PMID:26396926

  15. Prolactin-induced protein as a potential therapy response marker of adjuvant chemotherapy in breast cancer patients

    PubMed Central

    Jablonska, Karolina; Grzegrzolka, Jedrzej; Podhorska-Okolow, Marzenna; Stasiolek, Mariusz; Pula, Bartosz; Olbromski, Mateusz; Gomulkiewicz, Agnieszka; Piotrowska, Aleksandra; Rys, Janusz; Ambicka, Aleksandra; Ong, Siew Hwa; Zabel, Maciej; Dziegiel, Piotr

    2016-01-01

    Many studies are dedicated to exploring the molecular mechanisms of chemotherapy-resistance in breast cancer (BC). Some of them are focused on searching for candidate genes responsible for this process. The aim of this study was typing the candidate genes associated with the response to standard chemotherapy in the case of invasive ductal carcinoma. Frozen material from 28 biopsies obtained from IDC patients with different responses to chemotherapy were examined using gene expression microarray, Real-Time PCR (RT-PCR) and Western blot (WB). Based on the microarray results, further analysis of candidate gene expression was evaluated in 120 IDC cases by RT-PCR and in 224 IDC cases by immunohistochemistry (IHC). The results were correlated with clinical outcome and molecular subtype of the BC. Gene expression microarray revealed Prolactin-Induced Peptide (PIP) as a single gene differentially expressed in BC therapy responder or non-responder patients (p <0.05). The level of PIP expression was significantly higher in the BC therapy responder group than in the non-responder group at mRNA (p=0.0092) and protein level (p=0.0256). Expression of PIP mRNA was the highest in estrogen receptor positive (ER+) BC cases (p=0.0254) and it was the lowest in triple negative breast cancer (TNBC) (p=0.0336). Higher PIP mRNA expression was characterized by significantly longer disease free survival (DFS, p=0.0093), as well as metastasis free survival (MFS, p=0.0144). Additionally, PIP mRNA and PIP protein expression levels were significantly higher in luminal A than in other molecular subtypes and TNBC. Moreover significantly higher PIP expression was observed in G1, G2 vs. G3 cases (p=0.0027 and p=0.0013, respectively). Microarray analysis characterized PIP gene as a candidate for BC standard chemotherapy response marker. Analysis of clinical data suggests that PIP may be a good prognostic and predictive marker in IDC patients. Higher levels of PIP were related to longer DFS and MFS

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

    PubMed Central

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

    2015-01-01

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

  17. Radiofrequency Ablation–Induced Upregulation of Hypoxia-Inducible Factor-1α Can Be Suppressed with Adjuvant Bortezomib or Liposomal Chemotherapy

    PubMed Central

    Moussa, Marwan; Goldberg, S. Nahum; Kumar, Gaurav; Sawant, Rupa R.; Levchenko, Tatyana; Torchilin, Vladimir; Ahmed, Muneeb

    2014-01-01

    successfully suppressed with an adjuvant HIF-1α-specific inhibitor, bortezomib, or non–HIF-1α-specific liposomal chemotherapy. PMID:25439675

  18. The role of induction and adjuvant chemotherapy in combination with concurrent chemoradiotherapy for nasopharyngeal cancer: a Bayesian network meta-analysis of published randomized controlled trials

    PubMed Central

    Yu, Hongliang; Gu, Dayong; He, Xia; Gao, Xianshu; Bian, Xiuhua

    2016-01-01

    Whether the addition of induction chemotherapy (IC) or adjuvant chemotherapy (AC) to concurrent chemoradiotherapy (CCRT) is superior to CCRT alone for locally advanced nasopharyngeal cancer is unknown. A Bayesian network meta-analysis was performed to investigate the efficacy of CCRT, IC + CCRT, and CCRT + AC on locally advanced nasopharyngeal cancer. The overall survival (OS) with hazard ratios (HRs) and locoregional recurrence rates (LRRs) and distant metastasis rates (DMRs) with risk ratios (RRs) were investigated. After a comprehensive database search, eleven studies involving 2,626 assigned patients were included in this network meta-analysis. Compared with CCRT alone, IC + CCRT resulted in no significant improvement in OS or LRR and a marginal improvement in DMR (OS: HR =0.67, 95% credible interval (CrI) 0.32–1.18; LRR: RR =1.79, 95% CrI 0.80–3.51; DMR: RR =1.79, 95% CrI 0.24–1.04) and CCRT + AC exhibited no beneficial effects on any of the endpoints of OS, LRR, or DMR (OS: HR =0.99, 95% CrI 0.64–1.43; LRR: RR =0.78, 95% CrI 0.43–1.32; DMR: RR =0.85, 95% CrI 0.57–1.24). As a conclusion, for locally advanced nasopharyngeal cancer, no significant differences in the treatment efficacies of CCRT, IC + CCRT, and CCRT + AC were found, with the exception of a marginally significant improvement in distant control observed following IC + CCRT compared with CCRT alone. PMID:26793000

  19. A study of donepezil in female breast cancer survivors with self-reported cognitive dysfunction 1 to 5 years following adjuvant chemotherapy

    PubMed Central

    Griffin, L.; Balcueva, E. P.; Groteluschen, D. L.; Samuel, T. A.; Lesser, G. J.; Naughton, M. J.; Case, L. D.; Shaw, E. G.; Rapp, S. R.

    2016-01-01

    Purpose Some breast cancer survivors report cognitive difficulties greater than 1 year after chemotherapy. Acetylcholinesterase inhibitors (AChEI) may improve cognitive impairment. We conducted a randomized, placebo-controlled, pilot study to assess the feasibility of using the AChEI, donepezil, to improve subjective and objective measures of cognitive function in breast cancer survivors. Methods Women who received adjuvant chemotherapy 1–5 years prior with current cognitive dysfunction symptoms were randomized to 5 mg of donepezil/day vs placebo for 6 weeks and if tolerated 10 mg/day for 18 weeks for a total of 24 weeks. A battery of validated measures of attention, memory, language, visuomotor skills, processing speed, executive function, and motor dexterity and speed was administered at baseline and at 24 and 36 weeks. Subjective cognitive function, fatigue, sleep, mood, and health-related quality of life were evaluated at baseline and at 12, 24, and 36 weeks. Results Sixty-two patients were enrolled, 76 % completed the study, self-reported compliance was 98 %, and toxicities were minimal. At the end of treatment, the donepezil group performed significantly better than the control group on two parameters of memory—the Hopkins Verbal Learning Test -Revised (HVLT-R) Total Recall (p=0.033) and HVLT-R Discrimination (p=0.036). There were no significant differences on other cognitive variables or in subjective cognitive function or quality of life. Conclusion Accrual to this feasibility trial was robust, retention was good, compliance was excellent, and toxicities were minimal. Implications for Cancer Survivors Randomized clinical trials in breast cancer survivors to improve cognitive dysfunction are feasible. A phase III trial testing the efficacy of donepezil is warranted given these pilot results. PMID:26130292

  20. Feasibility of adjuvant chemotherapy with S-1 consisting of a 4-week administration and a two-week rest period in patients with completely resected non-small cell lung cancer

    PubMed Central

    OKUMURA, SHUNSUKE; SASAKI, TAKAAKI; SATOH, KAZUHIRO; KITADA, MASAHIRO; NAGASE, ATSUSHI; YATSUYANAGI, EIJI; OHSAKI, YOSHINOBU

    2013-01-01

    The efficacy of adjuvant chemotherapy with S-1 in patients with completely resected non-small cell lung cancer (NSCLC) has yet to be clarified, and the appropriate schedule for the adjuvant chemotherapy with S-1 remains unknown. A phase II study was conducted to evaluate the feasibility and efficacy of adjuvant chemotherapy with S-1. Patients enrolled in this study were 20–75 years old, had pathological stage IB-IIIA NSCLC, and had received complete resection of NSCLC. S-1 (80 mg/m2) was administered orally to the patients for four weeks followed by a two-week rest period (conventional schedule), for a maximum of eight cycles. The primary endpoint was relative dose intensity (RDI), while the secondary endpoints were safety and 1 year of disease-free survival (1y-DFS). Between May 2007 and October 2009, 28 patients were enrolled. The RDI was 63.1% (95% CI, 48.6–77.7). No grade 3 or worse hematological toxicity was observed. Grade 3 non-hematological toxicities were observed in four patients. No grade 4 or worse hematological toxicity was detected. The probability of 1y-DFS was 85.7% (95% CI, 72.8–98.6). In the subgroup analysis, the median RDI of patients over 65 years old was lower compared to the other patients (44.8 vs. 100%; P=0.013; Mann-Whitney U test). Creatinine clearance (CCr) was lower in the older group, with more grade 2 or 3 non-hematological toxicities in the elderly patients. These results suggest that the conventional schedule of adjuvant chemotherapy with S-1 is not likely to be feasible in older patients with completely resected NSCLC. PMID:24649134

  1. Feasibility and toxicity of adjuvant chemotherapy using S-1 granules for local advanced squamous cell carcinoma of the head and neck.

    PubMed

    Suzuki, Shinsuke; Honda, Kohei; Sato, Teruyuki; Yamazaki, Kazuharu; Ishikawa, Kazuo

    2015-10-01

    S-1 granulated powder has recently been released to the market as an additional format to that of the capsule. Patients who previously found it difficult to swallow the capsules are now able to take S-1 in powder form. This study evaluated the feasibility of S-1 granulated powder as adjuvant chemotherapy for advanced head and neck cancer. S-1 was orally administered for 2  weeks, followed by 1  week of rest (one course) for 12  months (16 courses). Twenty-four stage III and IV head and neck cancer patients were enrolled in this study. In total, 10 (47.6%) of the patients follow the planned schedule and dose. Severe adverse events were observed in 22 patients (91.7%), whereas no grade 4 adverse events were observed. S-1 granulated powder should be presented as an additional option for the treatment of head and neck cancer, especially for patients experiencing difficulty in swallowing oral medications. PMID:25971448

  2. Feasibility of oral administration of S-1 as adjuvant chemotherapy in gastric cancer: 4-week S-1 administration followed by 2-week rest vs. 2-week administration followed by 1-week rest

    PubMed Central

    YAMATSUJI, TOMOKI; FUJIWARA, YASUHIRO; MATSUMOTO, HIDEO; HATO, SHINJI; NAMIKAWA, TSUTOMU; HANAZAKI, KAZUHIRO; TAKAOKA, MUNENORI; HAYASHI, JIRO; SHIGEMITSU, KAORI; YOSHIDA, KAZUHIRO; URAKAMI, ATSUSHI; UNO, FUTOSHI; NISHIZAKI, MASAHIKO; KAGAWA, SHUNSUKE; NINOMIYA, MOTOKI; FUJIWARA, TOSHIYOSHI; HIRAI, TOSHIHIRO; NAKAMURA, MASAFUMI; HAISA, MINORU; NAOMOTO, YOSHIO

    2015-01-01

    In 2006, the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer (ACTS-GC) demonstrated that S-1 is an effective adjuvant therapy for gastric cancer. Following that study, S-1 has been used as the standard adjuvant therapy for gastric cancer in Japan. However, the 1-year completion rate was only 65.8% in the ACTS-GC study and feasibility remains a critical issue. We conducted a study to evaluate the feasibility of 2 weekly administration regimens of S-1 as adjuvant chemotherapy in gastric cancer. The criteria for eligibility included histologically proven stage II (excluding T1), IIIA or IIIB gastric cancer with D2 lymph-node dissection. The patients were randomly assigned to either arm A (S-1 administration for 4 weeks followed by 2 weeks of rest) or arm B (S-1 administration for 2 weeks followed by 1 week of rest). In each arm, treatment was continued for 12 months unless recurrence or severe adverse events were observed. The primary endpoint was feasibility (protocol treatment completion rate). The secondary endpoints were safety, relapse-free survival and overall survival. A total of 47 patients were assigned to arms A or B between May, 2008 and February, 2010. During the first interim analysis, the protocol treatment completion rates in arms A and B were 83 and 100%, respectively at 6 months and 49 and 89%, respectively, at 12 months (P=0.0046). Therefore, S-1 administration for 2 weeks followed by 1 week rest was more feasible as adjuvant chemotherapy in gastric cancer. Grade 3 adverse events in arm A included fatigue (8.0%), anorexia (8.0%), nausea (4.0%), vomiting (4.0%) and hand-foot syndrome (4.0%), whereas none were observed in arm B. There were no reported grade 4 adverse events in either arm. In conclusion, the 2-week S-1 administration followed by 1-week rest regimen appears to be a more feasible oral administration regimen for S-1 as adjuvant chemotherapy in gastric cancer. PMID:26137261

  3. 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. PMID:27138804

  4. Gemcitabine and cisplatin as neo-adjuvant chemotherapy for non-small cell lung cancer: a phase II study.

    PubMed

    Aydiner, Adnan; Kiyik, Murat; Cikrikcioglu, Saadettin; Kosar, Filiz; Gurses, Atilla; Turna, Akif; Yazar, Aziz; Dilege, Sukru; Goksel, Tuncay; Cakan, Alpaslan

    2007-11-01

    The combination of gemcitabine and cisplatin is one of the most active chemotherapy regimens against non-small cell lung cancer (NSCLC). This study was designed to evaluate the efficacy and safety of gemcitabine combined with cisplatin in a 3-week cycle regimen for patients with operable, early stage NSCLC. Gemcitabine at a dose of 1000 mg/m(2) on days 1 and 8 of each 21-day cycle for 3 cycles, followed by cisplatin at a dose of 75 mg/m(2) on day 1 was administered to patients with previously untreated, operable, early stage (IB-IIIA) NSCLC. A total of 47 patients (46 male, mean age 56.0+/-8.0 years) who met the eligibility criteria were enrolled. The pathological complete response rate was 5.3% of operated patients and 4.3% of total patients. At visit 4, 57.1% of the patients had partial response, 38.1%, stable disease and 4.8%, progressive disease. The main toxicities - leukopenia, neutropenia and thrombocytopenia - were usually clinically asymptomatic and did not require hospitalization. Non-hematological toxicities were minimal and manageable. Disease free and 12-month overall survival rates were over 70% and 80%, respectively. This study demonstrates that the administration of gemcitabine and cisplatin combination for 3 cycles is effective and tolerable for patients with operable, early stage NSCLC. Low toxicity profile and promising survival outcome suggest that this regimen has an encouraging activity in this subset of patients. PMID:17683827

  5. Fibroblastic growth factor receptor 1 amplification in osteosarcoma is associated with poor response to neo-adjuvant chemotherapy.

    PubMed

    Fernanda Amary, M; Ye, Hongtao; Berisha, Fitim; Khatri, Bhavisha; Forbes, Georgina; Lehovsky, Katie; Frezza, Anna M; Behjati, Sam; Tarpey, Patrick; Pillay, Nischalan; Campbell, Peter J; Tirabosco, Roberto; Presneau, Nadège; Strauss, Sandra J; Flanagan, Adrienne M

    2014-08-01

    Osteosarcoma, the most common primary bone sarcoma, is a genetically complex disease with no widely accepted biomarker to allow stratification of patients for treatment. After a recent report of one osteosarcoma cell line and one tumor exhibiting fibroblastic growth factor receptor 1 (FGFR1) gene amplification, the aim of this work was to assess the frequency of FGFR1 amplification in a larger cohort of osteosarcoma and to determine if this biomarker could be used for stratification of patients for treatment. About 352 osteosarcoma samples from 288 patients were analyzed for FGFR1 amplification by interphase fluorescence in situ hybridization. FGFR1 amplification was detected in 18.5% of patients whose tumors revealed a poor response to chemotherapy, and no patients whose tumors responded well to therapy harbored this genetic alteration. FGFR1 amplification is present disproportionately in the rarer histological variants of osteosarcoma. This study provides a rationale for inclusion of patients with osteosarcoma in clinical trials using FGFR kinase inhibitors. PMID:24861215

  6. Fibroblastic growth factor receptor 1 amplification in osteosarcoma is associated with poor response to neo-adjuvant chemotherapy

    PubMed Central

    Fernanda Amary, M; Ye, Hongtao; Berisha, Fitim; Khatri, Bhavisha; Forbes, Georgina; Lehovsky, Katie; Frezza, Anna M; Behjati, Sam; Tarpey, Patrick; Pillay, Nischalan; Campbell, Peter J; Tirabosco, Roberto; Presneau, Nadège; Strauss, Sandra J; Flanagan, Adrienne M

    2014-01-01

    Osteosarcoma, the most common primary bone sarcoma, is a genetically complex disease with no widely accepted biomarker to allow stratification of patients for treatment. After a recent report of one osteosarcoma cell line and one tumor exhibiting fibroblastic growth factor receptor 1 (FGFR1) gene amplification, the aim of this work was to assess the frequency of FGFR1 amplification in a larger cohort of osteosarcoma and to determine if this biomarker could be used for stratification of patients for treatment. About 352 osteosarcoma samples from 288 patients were analyzed for FGFR1 amplification by interphase fluorescence in situ hybridization. FGFR1 amplification was detected in 18.5% of patients whose tumors revealed a poor response to chemotherapy, and no patients whose tumors responded well to therapy harbored this genetic alteration. FGFR1 amplification is present disproportionately in the rarer histological variants of osteosarcoma. This study provides a rationale for inclusion of patients with osteosarcoma in clinical trials using FGFR kinase inhibitors. PMID:24861215

  7. Supratentorial primitive neuroectodermal tumors (S-PNET) in children: A prospective experience with adjuvant intensive chemotherapy and hyperfractionated accelerated radiotherapy

    SciTech Connect

    Massimino, Maura . E-mail: maura.massimino@istitutotumori.mi.it; Gandola, Lorenza; Spreafico, Filippo; Luksch, Roberto; Collini, Paola; Giangaspero, Felice; Simonetti, Fabio; Casanova, Michela; Cefalo, Graziella; Pignoli, Emanuele; Ferrari, Andrea; Terenziani, Monica; Podda, Marta; Meazza, Cristina; Polastri, Daniela; Poggi, Geraldina; Ravagnani, Fernando; Fossati-Bellani, Franca

    2006-03-15

    Purpose: Supratentorial primitive neuroectodermal tumors (S-PNET) are rare and have a grim prognosis, frequently taking an aggressive course with local relapse and metastatic spread. We report the results of a mono-institutional therapeutic trial. Methods and Materials: We enrolled 15 consecutive patients to preradiation chemotherapy (CT) consisting of high-dose methotrexate, high-dose etoposide, high-dose cyclophosphamide, and high-dose carboplatin, craniospinal irradiation (CSI) with hyperfractionated accelerated radiotherapy (HART) plus focal boost, maintenance with vincristine/lomustine or consolidation with high-dose thiotepa followed by autologous stem-cell rescue. Results: Median age was 9 years; 7 were male, 8 female. Site of disease was pineal in 3, elsewhere in 12. Six patients were had no evidence of disease after surgery (NED). Of those with evidence of disease after surgery (ED), 2 had central nervous system spread. Of the 9 ED patients, 2 had complete response (CR) and 2 partial response (PR) after CT, 4 stable disease, and 1 progressive disease. Of the 7 ED patients before radiotherapy, 1 had CR, 4 PR, and 2 minor response, thus obtaining a 44% CR + PR after CT and 71% after HART. Because of rapid progression in 2 of the first 5 patients, high-dose thiotepa was systematically adopted after HART in the subsequent 10 patients. Six of 15 patients relapsed (4 locally, 1 locally with dissemination, 1 with dissemination) a mean of 6 months after starting CT, 2 developed second tumors; 5 of 6 relapsers died at a median of 13 months. Three-year progression-free survival, event-free survival, and overall survival were 54%, 34%, and 61%, respectively. Conclusion: Hyperfractionated accelerated RT was the main tool in obtaining responses in S-PNET; introducing the myeloablative phase improved the prognosis (3/10 vs. 3/5 relapses), though the outcome remained unsatisfactory despite the adoption of this intensive treatment.

  8. Design of the Physical exercise during Adjuvant Chemotherapy Effectiveness Study (PACES):A randomized controlled trial to evaluate effectiveness and cost-effectiveness of physical exercise in improving physical fitness and reducing fatigue

    PubMed Central

    2010-01-01

    Background Cancer chemotherapy is frequently associated with a decline in general physical condition, exercise tolerance, and muscle strength and with an increase in fatigue. While accumulating evidence suggests that physical activity and exercise interventions during chemotherapy treatment may contribute to maintaining cardiorespiratory fitness and strength, the results of studies conducted to date have not been consistent. Additional research is needed to determine the optimal intensity of exercise training programs in general and in particular the relative effectiveness of supervised, outpatient (hospital- or physical therapy practice-based) versus home-based programs. Methods This multicenter, prospective, randomized trial will evaluate the effectiveness of a low to moderate intensity, home-based, self-management physical activity program, and a high intensity, structured, supervised exercise program, in maintaining or enhancing physical fitness (cardiorespiratory fitness and muscle strength), in minimizing fatigue and in enhancing the health-related quality of life (HRQoL). Patients receiving adjuvant chemotherapy for breast or colon cancer (n = 360) are being recruited from twelve hospitals in the Netherlands, and randomly allocated to one of the two treatment groups or to a 'usual care' control group. Performance-based and self-reported outcomes are assessed at baseline, at the end of chemotherapy and at six month follow-up. Discussion This large, multicenter, randomized clinical trial will provide additional empirical evidence regarding the effectiveness of physical exercise during adjuvant chemotherapy in enhancing physical fitness, minimizing fatigue, and maintaining or enhancing patients' quality of life. If demonstrated to be effective, exercise intervention programs will be a welcome addition to the standard program of care offered to patients with cancer receiving chemotherapy. Trial registration This study is registered at the Netherlands Trial

  9. Definitive Results of a Phase III Adjuvant Trial Comparing Three Chemotherapy Regimens in Women With Operable, Node-Positive Breast Cancer: The NSABP B-38 Trial

    PubMed Central

    Swain, Sandra M.; Tang, Gong; Geyer, Charles E.; Rastogi, Priya; Atkins, James N.; Donnellan, Paul P.; Fehrenbacher, Louis; Azar, Catherine A.; Robidoux, André; Polikoff, Jonathan A.; Brufsky, Adam M.; Biggs, David D.; Levine, Edward A.; Zapas, John L.; Provencher, Louise; Northfelt, Donald W.; Paik, Soonmyung; Costantino, Joseph P.; Mamounas, Eleftherios P.; Wolmark, Norman

    2013-01-01

    Purpose Anthracycline- and taxane-based three-drug chemotherapy regimens have proven benefit as adjuvant therapy for early-stage breast cancer. This trial (NSABP B-38; Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Positive Breast Cancer) asked whether the incorporation of a fourth drug could improve outcomes relative to two standard regimens and provided a direct comparison of those two regimens. Patients and Methods We randomly assigned 4,894 women with node-positive early-stage breast cancer to six cycles of docetaxel, doxorubicin, and cyclophosphamide (TAC), four cycles of dose-dense (DD) doxorubicin and cyclophosphamide followed by four cycles of DD paclitaxel (P; DD AC→P), or DD AC→P with four cycles of gemcitabine (G) added to the DD paclitaxel (DD AC→PG). Primary granulocyte colony-stimulating factor support was required; erythropoiesis-stimulating agents (ESAs) were used at the investigator's discretion. Results There were no significant differences in 5-year disease-free survival (DFS) between DD AC→PG and DD AC→P (80.6% v 82.2%; HR, 1.07; P = .41), between DD AC→PG and TAC (80.6% v 80.1%; HR, 0.93; P = .39), in 5-year overall survival (OS) between DD AC→PG and DD AC→P (90.8% v 89.1%; HR, 0.85; P = .13), between DD AC→PG and TAC (90.8% v 89.6%; HR, 0.86; P = .17), or between DD AC→P versus TAC for DFS (HR, 0.87; P = .07) and OS (HR, 1.01; P = .96). Grade 3 to 4 toxicities for TAC, DD AC→P, and DD AC→PG, respectively, were febrile neutropenia (9%, 3%, 3%; P < .001), sensory neuropathy (< 1%, 7%, 6%; P < .001), and diarrhea (7%, 2%, 2%; P < .001). Exploratory analyses for ESAs showed no association with DFS events (HR, 1.02; P = .95). Conclusion Adding G to DD AC→P did not improve outcomes. No significant differences in efficacy were identified between DD AC→P and TAC, although toxicity profiles differed. PMID:23940225

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

    PubMed

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

    2015-10-01

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

  11. Benefit of Adjuvant Chemotherapy and Pelvic Lymph Node Dissection in pT3 and Node Positive Bladder Cancer Patients Treated with Radical Cystectomy

    PubMed Central

    Boström, Peter J.; Mirtti, Tuomas; van Rhijn, Bas; Fleshner, Neil E.; Finelli, Antonio; Laato, Matti; Jewett, Michael A.; Moore, Malcom J.; Sridhar, Srikala; Nurmi, Martti; Tannock, Ian F.; Zlotta, Alexandre R.

    2016-01-01

    Background: Benefits of adjuvant chemotherapy (AC) and extent of pelvic lymph node dissection (PLND) in radical cystectomy (RC) are debated. Results from randomized trials are still expected. Objective: To analyze the effects of AC and PLND in two academic centers with opposite policies regarding their use. Methods: 581 bladder cancer patients who underwent RC without neoadjuvant chemotherapy, from Toronto (University Health Network), Canada, and Turku University Hospital, Finland were included. Disease specific survival (DSS) and failure patterns were assessed. Results: Centers differed in PLND rate (93% and 36% in Toronto and Turku respectively, p <  0.001), PLND extent (≥10 removed nodes, 58% vs. 8%, p <  0.001) and AC rate (21% vs. 2%, p <  0.001). Survival between centers among pT≤1 or pT4 patients was similar. pT3 patients in Toronto had an improved 10 year DSS (43% vs. 22%, p = 0.025). Distant failures were less common after AC (HR 0.56, 95%  CI 0.33–0.98, p <  0.042). In node positive (N+) patients, mortality was significantly higher in Turku (HR 2.19, 95%  CI 1.44–3.34, p <  0.001) and lower in patients receiving AC (HR 0.60, 95%  CI 0.37–0.99, p = 0.044). 41% DSS at 10 years was observed in N+ Toronto patients. Limitations included the non-randomized retrospective design and absence of propensity score analysis. Conclusion: Combining AC and PLND to RC is associated with improved survival in pT3 and N+ patients. PLND did not affect survival independently but helps in selecting patients for AC. Our data adds to the growing body of evidence supporting the usefulness of AC in addition to PLND in high risk patients operated by cystectomy. PMID:27376145

  12. Is TIMP-1 immunoreactivity alone or in combination with other markers a predictor of benefit from anthracyclines in the BR9601 adjuvant breast cancer chemotherapy trial?

    PubMed Central

    2013-01-01

    Introduction Predictive cancer biomarkers to guide the right treatment to the right patient at the right time are strongly needed. The purpose of the present study was to validate prior results that tissue inhibitor of metalloproteinase 1 (TIMP-1) alone or in combination with either HER2 or TOP2A copy number can be used to predict benefit from epirubicin (E) containing chemotherapy compared with cyclophosphamide, methotrexate and fluorouracil (CMF) treatment. Methods For the purpose of this study, formalin fixed paraffin embedded tumor tissue from women recruited into the BR9601 clinical trial, which randomized patients to E-CMF versus CMF, were analyzed for TIMP-1 immunoreactivity. Using previously collected data for HER2 amplification and TOP2A gene aberrations, we defined patients as "anthracycline non-responsive", that is, 2T (TIMP-1 immunoreactive and TOP2A normal) and HT (TIMP-1 immunoreactive and HER2 negative) and anthracycline responsive (all other cases). Results In total, 288 tumors were available for TIMP-1 analysis with (183/274) 66.8%, and (181/274) 66.0% being classed as 2T and HT responsive, respectively. TIMP-1 was neither associated with patient prognosis (relapse free survival or overall survival) nor with a differential effect of E-CMF and CMF. Also, TIMP-1 did not add to the predictive value of HER2, TOP2A gene aberrations, or to Ki67 immunoreactivity. Conclusion This study could not confirm the predictive value of TIMP-1 immunoreactivity in patients randomized to receive E-CMF versus CMF as adjuvant treatment for primary breast cancer. PMID:23570501

  13. Expression of Folate Pathway Genes in Stage III Colorectal Cancer Correlates with Recurrence Status Following Adjuvant Bolus 5-FU-Based Chemotherapy

    PubMed Central

    Odin, Elisabeth; Sondén, Arvid; Gustavsson, Bengt; Carlsson, Göran; Wettergren, Yvonne

    2015-01-01

    Colorectal cancer is commonly treated with 5-fluorouracil and 5-formyltetrahydrofolate (leucovorin). Metabolic action of leucovorin requires several enzymatic steps that are dependent on expression of corresponding coding genes. To identify folate pathway genes with possible impact on leucovorin metabolism, a retrospective study was performed on 193 patients with stage III colorectal cancer. Relative expression of 22 genes putatively involved in leucovorin transport, polyglutamation and metabolism was determined in tumor and mucosa samples using quantitative real-time polymerase chain reaction. After surgery, patients received adjuvant 5-fluorouracil-based bolus chemotherapy with leucovorin during six months, and were followed for 3 to 5 years. Cox regression analysis showed that high tumoral expression of the genes SLC46A1/PCFT (proton-coupled folate transporter) and SLC19A1/RFC-1 (reduced folate carrier 1) correlated significantly (p < 0.001 and p < 0.01, respectively) with a decreased risk of recurrent disease, measured as disease-free survival (DFS). These two genes are involved in the transport of folates into the cells and each functions optimally at a different pH. We conclude that SLC46A1/PCFT and SLC19A1/RFC-1 are associated with DFS of patients with colorectal cancer and hypothesize that poor response to 5-fluorouracil plus leucovorin therapy in some patients may be linked to low expression of these genes. Such patients might need a more intensified therapeutic approach than those with high gene expression. Future prospective studies will determine if the expression of any of these genes can be used to predict response to leucovorin. PMID:26193446

  14. Concurrent administration of adjuvant chemotherapy and radiotherapy after breast-conserving surgery enhances late toxicities: Long-term results of the ARCOSEIN multicenter randomized study

    SciTech Connect

    Toledano, Alain . E-mail: alain.toledano@gmail.com; Garaud, Pascal; Serin, Daniel; Fourquet, Alain; Bosset, Jean-Francois; Breteau, Noel; Body, Gilles; Azria, David; Le Floch, Olivier; Calais, Gilles

    2006-06-01

    Purpose: In 1996, a multicenter randomized study was initiated that compared sequential vs. concurrent adjuvant chemotherapy (CT) with radiation therapy (RT) after breast-conserving surgery (ARCOSEIN study). After a median follow-up of 6.7 years (range, 4.3-9 years), we decided to prospectively evaluate the late effects of these 2 strategies. Methods and Materials: A total of 297 patients from the 5 larger participating institutions were asked to report for a follow-up examination. Seventy-two percent (214 patients) were eligible for evaluation of late toxicity. After breast-conserving surgery, patients were treated either with sequential treatment with CT first followed by RT (Arm A) or CT administered concurrently with RT (Arm B). In all patients, CT regimen consisted of mitoxantrone (12 mg/m{sup 2}), 5-FU (500 mg/m{sup 2}), and cyclophosphamide (500 mg/m{sup 2}), 6 cycles (Day 1 to Day 21). Conventional RT was delivered to the whole breast by administration of a 2 Gy per fraction protocol to a total dose of 50 Gy ({+-} boost to the primary tumor bed). The assessment of toxicity was blinded to treatment and was graded by the radiation oncologist, according to the LENT/SOMA scale. Skin pigmentation was also evaluated according to a personal 5-points scoring system (excellent, good, moderate, poor, very poor). Results: Among the 214 evaluable patients, 107 were treated in each arm. The 2 populations were homogeneous for patient, tumor, and treatment characteristics. Subcutaneous fibrosis (SF), telangectasia (T), skin pigmentation (SP), and breast atrophy (BA) were significantly increased in Arm B. No statistical difference was observed between the 2 arms of the study concerning Grade 2 or higher pain, breast edema, or lymphedema. No deaths were caused by late toxicity. Conclusion: After breast-conserving surgery, the concurrent use of CT with RT is significantly associated with an increase incidence of Grade 2 or greater late side effects.

  15. Expression of Folate Pathway Genes in Stage III Colorectal Cancer Correlates with Recurrence Status Following Adjuvant Bolus 5-FU-Based Chemotherapy.

    PubMed

    Odin, Elisabeth; Sondén, Arvid; Gustavsson, Bengt; Carlsson, Göran; Wettergren, Yvonne

    2015-01-01

    Colorectal cancer is commonly treated with 5-fluorouracil and 5-formyltetrahydrofolate (leucovorin). Metabolic action of leucovorin requires several enzymatic steps that are dependent on expression of corresponding coding genes. To identify folate pathway genes with possible impact on leucovorin metabolism, a retrospective study was performed on 193 patients with stage III colorectal cancer. Relative expression of 22 genes putatively involved in leucovorin transport, polyglutamation and metabolism was determined in tumor and mucosa samples using quantitative real-time polymerase chain reaction. After surgery, patients received adjuvant 5-fluorouracil-based bolus chemotherapy with leucovorin during six months, and were followed for 3 to 5 years. Cox regression analysis showed that high tumoral expression of the genes SLC46A1/PCFT (proton-coupled folate transporter) and SLC19A1/RFC-1 (reduced folate carrier 1) correlated significantly (p < 0.001 and p < 0.01, respectively) with a decreased risk of recurrent disease, measured as disease-free survival (DFS). These two genes are involved in the transport of folates into the cells and each functions optimally at a different pH. We conclude that SLC46A1/PCFT and SLC19A1/RFC-1 are associated with DFS of patients with colorectal cancer and hypothesize that poor response to 5-fluorouracil plus leucovorin therapy in some patients may be linked to low expression of these genes. Such patients might need a more intensified therapeutic approach than those with high gene expression. Future prospective studies will determine if the expression of any of these genes can be used to predict response to leucovorin. PMID:26193446

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

    PubMed

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

    2014-04-01

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

  17. Prognostic significance of S100A4 expression in stage II and III colorectal cancer: results from a population-based series and a randomized phase III study on adjuvant chemotherapy.

    PubMed

    Boye, Kjetil; Jacob, Havjin; Frikstad, Kari-Anne M; Nesland, Jahn M; Maelandsmo, Gunhild M; Dahl, Olav; Nesbakken, Arild; Flatmark, Kjersti

    2016-08-01

    Current clinical algorithms are unable to precisely predict which colorectal cancer patients would benefit from adjuvant chemotherapy, and there is a need for novel biomarkers to improve the selection of patients. The metastasis-promoting protein S100A4 predicts poor outcome in colorectal cancer, but whether it could be used to guide clinical decision making remains to be resolved. S100A4 expression was analyzed by immunohistochemistry in primary colorectal carcinomas from a consecutively collected, population-representative cohort and a randomized phase III study on adjuvant 5-fluorouracil/levamisole. Sensitivity to treatment with 5-fluorouracil in S100A4 knockdown cells was investigated using 2D and 3D cell culture assays. Strong nuclear expression of S100A4 was detected in 19% and 23% of the tumors in the two study cohorts, respectively. In both cohorts, nuclear immunoreactivity was associated with reduced relapse-free (P < 0.001 and P = 0.010) and overall survival (P = 0.046 and P = 0.006) in univariate analysis. In multivariate analysis, nuclear S100A4 was a predictor of poor relapse-free survival in the consecutive series (P = 0.002; HR 1.9), but not in the randomized study. Sensitivity to treatment with 5-fluorouracil was not affected by S100A4 expression in in vitro cell culture assays, and there was no indication from subgroup analyses in the randomized study that S100A4 expression was associated with increased benefit of adjuvant treatment with 5-fluorouracil/levamisole. The present study confirms that nuclear S100A4 expression is a negative prognostic biomarker in colorectal cancer, but the clinical utility in selection of patients for adjuvant fluoropyrimidine-based chemotherapy is limited. PMID:27273130

  18. Randomized phase III trial of treatment duration for oral uracil and tegafur plus leucovorin as adjuvant chemotherapy for patients with stage IIB/III colon cancer: final results of JFMC33-0502

    PubMed Central

    Sadahiro, S.; Tsuchiya, T.; Sasaki, K.; Kondo, K.; Katsumata, K.; Nishimura, G.; Kakeji, Y.; Baba, H.; Sato, S.; Koda, K.; Yamaguchi, Y.; Morita, T.; Matsuoka, J.; Usuki, H.; Hamada, C.; Kodaira, S.

    2015-01-01

    Background While adjuvant chemotherapy is preferable for high-risk colon cancer, treatment duration is controversial. Oral uracil and tegafur (UFT)/leucovorin (LV) is widely used as a standard adjuvant chemotherapy for colon cancer in Japan. We conducted a phase III trial to investigate the optimal duration of adjuvant chemotherapy for stage IIB/III colon cancer. Patients and methods Patients with curatively resected stage IIB/III colon cancer were eligible for enrollment in this trial. Patients were registered within 6 weeks after surgery and were randomly assigned to receive UFT/LV for 28 of 35 days for 6 months in the control group or for 5 consecutive days per week for 18 months in the study group. The primary end point was the disease-free survival (DFS), and the secondary end points were overall survival (OS) and safety. Result A total of 1071 patients were registered from 233 centers. A statistically significant difference in DFS was not observed between the study group and the control group; the 5-year DFS was 69% in the study group and 69% in the control group. The 5-year OS was 85% in the study group and 85% in the control group. Conclusion Eighteen-month treatment with UFT/LV did not improve DFS or OS compared with 6-month UFT/LV treatment in patients with stage IIB/III colon cancer. The important finding from this study is that not 18 months but 6 months of treatment is enough for postoperative UFT/LV for stage IIB/III colon cancer. Clinical trial number UMIN-CTR C000000245. PMID:26347106

  19. Comparison of the effectiveness and toxicity of neoadjuvant chemotherapy regimens, capecitabine/epirubicin/cyclophosphamide vs 5-fluorouracil/epirubicin/cyclophosphamide, followed by adjuvant, capecitabine/docetaxel vs docetaxel, in patients with operable breast cancer

    PubMed Central

    Zhang, Minmin; Wei, Wei; Liu, Jianlun; Yang, Huawei; Jiang, Yi; Tang, Wei; Li, Qiuyun; Liao, Xiaoming

    2016-01-01

    The aim of this study was to compare the effectiveness and toxicity of neoadjuvant chemotherapy regimens, xeloda/epirubicin/cyclophosphamide (XEC) vs 5-fluorouracil/epirubicin/cyclophosphamide (FEC), followed by adjuvant chemotherapy regimens, capecitabine/taxotere (XT) vs taxotere (T), in axillary lymph node (LN)-positive early-stage breast cancer. In this randomized, Phase III trial, 137 patients with operable primary breast cancer (T2-0, N0-1) who were tested axillary LN positive through aspiration biopsy of axillary LNs were randomized (1:1) to four 3-weekly cycles of XEC or FEC. Patients underwent surgery within 4–6 weeks after the fourth cycle, followed by four adjuvant cycles of 3-weekly XT or T. The primary end point was tumor pathological complete response. Toxicity profiles were secondary objectives. In total, 131 patients had clinical and radiological evaluation of response and underwent surgery. Treatment with XEC led to an increased rate of pathological complete response in primary tumor (18% vs 6%, respectively, P=0.027) and objective remission rate (87% vs 73%, P=0.048) compared to FEC. Clinical complete response occurred in 20% and 7% for XEC and FEC, respectively. Compared to FEC, XEC was associated with more hand-foot syndrome (57% vs 11%, P<0.001) and 3/4 grade nausea/vomiting/diarrhea (30% vs 14%, P=0.034) but less phlebitis (3% vs 14%, P=0.035). XT and T adjuvant chemotherapy regimens were well tolerated: treatment-related 3/4 grade adverse events occurred in 28% and 17% of patients receiving XT and T, respectively. PMID:27354816

  20. Comparison of the effectiveness and toxicity of neoadjuvant chemotherapy regimens, capecitabine/epirubicin/cyclophosphamide vs 5-fluorouracil/epirubicin/cyclophosphamide, followed by adjuvant, capecitabine/docetaxel vs docetaxel, in patients with operable breast cancer.

    PubMed

    Zhang, Minmin; Wei, Wei; Liu, Jianlun; Yang, Huawei; Jiang, Yi; Tang, Wei; Li, Qiuyun; Liao, Xiaoming

    2016-01-01

    The aim of this study was to compare the effectiveness and toxicity of neoadjuvant chemotherapy regimens, xeloda/epirubicin/cyclophosphamide (XEC) vs 5-fluorouracil/epirubicin/cyclophosphamide (FEC), followed by adjuvant chemotherapy regimens, capecitabine/taxotere (XT) vs taxotere (T), in axillary lymph node (LN)-positive early-stage breast cancer. In this randomized, Phase III trial, 137 patients with operable primary breast cancer (T2-0, N0-1) who were tested axillary LN positive through aspiration biopsy of axillary LNs were randomized (1:1) to four 3-weekly cycles of XEC or FEC. Patients underwent surgery within 4-6 weeks after the fourth cycle, followed by four adjuvant cycles of 3-weekly XT or T. The primary end point was tumor pathological complete response. Toxicity profiles were secondary objectives. In total, 131 patients had clinical and radiological evaluation of response and underwent surgery. Treatment with XEC led to an increased rate of pathological complete response in primary tumor (18% vs 6%, respectively, P=0.027) and objective remission rate (87% vs 73%, P=0.048) compared to FEC. Clinical complete response occurred in 20% and 7% for XEC and FEC, respectively. Compared to FEC, XEC was associated with more hand-foot syndrome (57% vs 11%, P<0.001) and 3/4 grade nausea/vomiting/diarrhea (30% vs 14%, P=0.034) but less phlebitis (3% vs 14%, P=0.035). XT and T adjuvant chemotherapy regimens were well tolerated: treatment-related 3/4 grade adverse events occurred in 28% and 17% of patients receiving XT and T, respectively. PMID:27354816

  1. CT-Guided Wire Localization for Involved Axillary Lymph Nodes After Neo-adjuvant Chemotherapy in Patients With Initially Node-Positive Breast Cancer.

    PubMed

    Trinh, Long; Miyake, Kanae K; Dirbas, Frederick M; Kothary, Nishita; Horst, Kathleen C; Lipson, Jafi A; Carpenter, Catherine; Thompson, Atalie C; Ikeda, Debra M

    2016-07-01

    Resection of biopsy-proven involved axillary lymph nodes (iALNs) is important to reduce the false-negative rates of sentinel lymph node (SLN) biopsy after neo-adjuvant chemotherapy (NAC) in patients with initially node-positive breast cancer. Preoperative wire localization for iALNs marked with clips placed during biopsy is a technique that may help the removal of iALNs after NAC. However, ultrasound (US)-guided localization is often difficult because the clips cannot always be reliably visible on US. Computed tomography (CT)-guided wire localization can be used; however, to date there have been no reports on CT-guided wire localization for iALNs. The aim of this study was to describe a series of patients who received CT-guided wire localization for iALN removal after NAC and to evaluate the feasibility of this technique. We retrospectively analyzed five women with initially node-positive breast cancer (age, 41-52 years) who were scheduled for SLN biopsy after NAC and received preoperative CT-guided wire localization for iALNs. CT visualized all the clips that were not identified on post-NAC US. The wire tip was deployed beyond or at the target, with the shortest distance between the wire and the index clip ranging from 0 to 2.5 mm. The total procedure time was 21-38 minutes with good patient tolerance and no complications. In four of five cases, CT wire localization aided in identification and resection of iALNs that were not identified with lymphatic mapping. Residual nodal disease was confirmed in two cases: both had residual disease in wire-localized lymph nodes in addition to SLNs. Although further studies with more cases are required, our results suggest that CT-guided wire localization for iALNs is a feasible technique that facilitates identification and removal of the iALNs as part of SLN biopsy after NAC in situations where US localization is unsuccessful. PMID:27061012

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

    PubMed

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

    2016-07-01

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

  3. Tissue and Serum miRNA Profile in Locally Advanced Breast Cancer (LABC) in Response to Neo-Adjuvant Chemotherapy (NAC) Treatment

    PubMed Central

    Al-Khanbashi, Manal; Caramuta, Stefano; Alajmi, Adil M.; Al-Haddabi, Ibrahim; Al-Riyami, Marwa; Lui, Weng-Onn; Al-Moundhri, Mansour S.

    2016-01-01

    Introduction MicroRNAs (miRNAs) are small non-coding RNA that plays a vital role in cancer progression. Neo-adjuvant chemotherapy (NAC) has become the standard of care for locally advanced breast cancer. The aim of this study was to evaluate miRNA alterations during NAC using multiple samples of tissue and serum to correlate miRNA expression with clinico-pathological features and patient outcomes. Methods Tissue and serum samples were collected from patients with locally advanced breast cancer undergoing NAC at four time points: time of diagnosis, after the first and fourth cycle of doxorubicin/cyclophosphamide treatment, and after the fourth cycle of docetaxel administration. First, we evaluated the miRNA expression profiles in tissue and correlated expression with clinico-pathological features. Then, a panel of four miRNAs (miR-451, miR-3200, miR-21, and miR-205) in serum samples was further validated using quantitative reverse-transcription polymerase chain reaction (RT-qPCR). The alterations in serum levels of miRNA, associations with clinical and pathological responses, correlation with clinico-pathological features, and survival outcomes were studied using Friedman, Mann-Whitney U, and Spearman, Wilcoxon signed-ranks tests. P≤0.05 was considered statistically significant. Results We analyzed 72 tissue samples and 108 serum samples from 9 patients and 27 patients, respectively. MicroRNA expression profiling of tumor versus normal tissue revealed more than 100 differentially expressed miRNAs. Serum miR-451 levels were significantly decreased during treatment, and higher serum levels were associated with improved clinical and pathological responses and disease-free survival. This is one of the early reports on miR-3200 in response to treatment in breast cancer, as serum levels of miR-3200 found to decline during NAC, and higher serum levels were associated with lower residual breast cancer burden and relapse rates at time of diagnosis. Conclusion Variations in

  4. West Midlands Oncology Association trials of adjuvant chemotherapy in operable breast cancer: results after a median follow-up of 7 years. I. Patients with involved axillary lymph nodes.

    PubMed Central

    Morrison, J. M.; Howell, A.; Kelly, K. A.; Grieve, R. J.; Monypenny, I. J.; Walker, R. A.; Waterhouse, J. A.

    1989-01-01

    The aim of this study was to test the effectiveness of a regimen of combination chemotherapy known to be active in advanced breast cancer when given as an adjuvant treatment after mastectomy. A total of 569 patients with cancer of the breast and involvement of axillary lymph nodes were randomised, after simple mastectomy with axillary sampling, to receive either no adjuvant treatment or intravenous adriamycin 50 mg, vincristine 1 mg, cyclophosphamide 250 mg, methotrexate 150 mg and fluorouracil 250 mg (AVCMF) every 21 days for eight cycles. Randomisation was stratified according to menopausal status and tumour size. Treatment was started within 14 days of surgery in 94% of patients. Eighty-eight per cent of patients received at least seven cycles of chemotherapy with no dose reduction. The median relapse-free survival was prolonged by 14 months in patients treated with AVCMF (chi2 1 = 11.7; P = 0.0006). In the premenopausal group this period was 17 months (chi2 1 = 8.8; P = 0.003) compared with 8 months in the post-menopausal group (chi2 1 = 3.3; P = 0.07). Neither overall survival nor survival in these subgroups was significantly influenced by treatment. PMID:2690913

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

    PubMed

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

    2014-02-01

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

  6. Five-Year Results From a Scandinavian Sarcoma Group Study (SSG XIII) of Adjuvant Chemotherapy Combined With Accelerated Radiotherapy in High-Risk Soft Tissue Sarcoma of Extremities and Trunk Wall

    SciTech Connect

    Jebsen, Nina L.; Bruland, Oyvind S.; Eriksson, Mikael; Engellau, Jacob; Turesson, Ingela; Folin, Annika; Trovik, Clement S.; Hall, Kirsten Sundby

    2011-12-01

    Purpose: To evaluate adjuvant chemotherapy and interpolated accelerated radiotherapy (RT) for adult patients with high-risk soft tissue sarcoma in the extremities or trunk wall. Methods and Materials: High-risk soft tissue sarcoma was defined as high-grade malignancy and at least two of the following criteria: size {>=}8 cm, vascular invasion, or necrosis. Six cycles of doxorubicin and ifosfamide were prescribed for all patients. RT to a total dose of 36 Gy (1.8 Gy twice daily) was inserted between two chemotherapy cycles after marginal margin resection regardless of tumor depth or after wide-margin resection for deep-seated tumors. RT was boosted to 45 Gy in a split-course design in the case of intralesional margin resection. Results: A total of 119 patients were eligible, with a median follow-up of 5 years. The 5-year estimate of the local recurrence, metastasis-free survival, and overall survival rate was 12%, 59%, and 68%, respectively. The group receiving RT to 36 Gy had a local recurrence rate of 10%. In contrast, the local recurrence rate was 29% in the group treated with RT to 45 Gy. The presence of vascular invasion and low chemotherapy dose intensity had a negative effect on metastasis-free and overall survival. Toxicity was moderate after both the chemotherapy and the RT. Conclusions: Accelerated RT interposed between chemotherapy cycles in a selected population of patients with high-risk soft tissue sarcoma resulted in good local and distant disease control, with acceptable treatment-related morbidity. The greater radiation dose administered after intralesional surgery was not sufficient to compensate for the poorer surgical margin. Vascular invasion was the most important prognostic factor for metastasis-free and overall survival.

  7. The treatment of soft-tissue sarcomas of the extremities - prospective randomized evaluations of (1) limb-sparing surgery plus radiation therapy compared with amputation and (2) the role of adjuvant chemotherapy

    SciTech Connect

    Rosenberg, S.A.; Tepper, J.; Glatstein, E.

    1982-09-01

    Between May 1975 and April 1981, 43 adult patients with high-grade soft tissue sarcomas of the extremities were prospectively randomized to receive either amputation at or above the joint proximal to the tumor, including all involved muscle groups, or to receive a limb-sparing resection plus adjuvant radiation therapy. The limb-sparing resection group received wide local excision followed by 5000 rads to the entire anatomic area at risk for local spread and 6000 to 7000 rads to the tumor bed. Both randomization groups received postoperative chemotherapy with doxorubicin (maximum cumulative dose 550 mg/m/sup 2/), cyclophosphamide, and high-dose methotrexate. Twenty-seven patients randomized to receive limb-sparing resection and radiotherapy, and 16 received amputation (randomization was 2:1). There were four local recurrences in the limb-sparing group and none in the amputation group (p/sub 1/ = 0.06 generalized Wilcoxon test). However, there were no differences in disease-free survival rates (83% and 88% at five years; p/sub 2/ = 0.99) between the limb-sparing group and the amputation treatment groups. Multivariate analysis indicated that the only correlate of local recurrence was the final margin of resection. Patients with positive margins of resection had a higher likelihood of local recurrence compared with those with negative margins (p/sub 1/ < 0.00001) even when postoperative radiotherapy was used. A simultaneous prospective randomized study of postoperative chemotherapy in 65 patients with high-grade soft-tissue sarcomas of the extremities revealed a marked advantage in patients receiving chemotherapy compared with those without chemotherapy in three-year continuous disease-free (92% vs. 60%; p/sub 1/ = 0.00008) and overall survival (95% vs. 74%; p/sub 1/ = 0.04).

  8. Exploration of optimal time for initiating adjuvant chemotherapy after surgical resection: A retrospective study in Chinese patients with stage IIIA non‐small cell lung cancer in a single center

    PubMed Central

    Zhu, Yixiang; Zhai, Xiaoyu; Chen, Sipeng

    2016-01-01

    Abstract Background Adjuvant chemotherapy (ACT) can reduce the risk of recurrence and improve survival after surgical resection in non‐small cell lung cancer (NSCLC) patients. We explore the optimal time from surgery to initiation of ACT in Chinese patients with stage IIIA NSCLC. Methods Patients pathologically diagnosed with IIIA NSCLC who underwent radical surgery were included in this study. The cut‐off point of time to initiation of adjuvant chemotherapy (TTAC) was determined by maximally selected log‐rank statistics. Patients were divided into two groups according to the TTAC cut‐off point. Propensity score matching (PSM) was used to eliminate confounding variables, and Kaplan–Meier analysis was used to analyze the impact of TTAC on disease‐free survival (DFS). Results The cut‐off time was 46 days from surgery to the first ACT. Prior to PSM, baseline characteristic variables were balanced with no statistical difference between the groups, except for pathologic subtype and smoking history. No difference in DFS was found between the two groups prior to PSM (P = 0.529); after PSM, the median DFS was consistent between the two (P = 0.822). N2 lymph node station involvement was an independent factor associated with poor survival compared with patients with N0 lymph node involvement. Moderate differentiation and postoperative radiotherapy could improve survival; however, TTAC was not significantly correlated with DFS. Subgroup analyses showed no significant correlation between DFS and different TTAC programs. Conclusion No survival difference was obtained as to when ACT was initiated for patients with stage IIIA NSCLC.

  9. Is epirubicin effective in first-line chemotherapy of metastatic breast cancer (MBC) after an epirubicin-containing adjuvant treatment? A single centre phase III trial

    PubMed Central

    Pacilio, C; Morabito, A; Nuzzo, F; Gravina, A; Labonia, V; Landi, G; Rossi, E; De Maio, E; Di Maio, M; D'aiuto, G; Botti, G; Normanno, N; Chiodini, P; Gallo, C; Perrone, F; de Matteis, A

    2006-01-01

    The aim of the study was to demonstrate the superiority of docetaxel and epirubicin vs docetaxel alone as first-line therapy in metastatic breast cancer patients pretreated with adjuvant or neoadjuvant epirubicin. We compared single agent docetaxel 100 mg m−2 (D) with the combination of docetaxel 80 mg m−2 and epirubicin 75 mg m−2 (ED). The response rate (72 vs 79%), the progression-free survival (median 9 vs 11 months) and the overall survival (median 18 vs 21 months) were not significantly different between the ED (n=26) and D arms (n=25), respectively. Leucopaenia, nausea and stomatitis were significantly worse with ED. In conclusion, epirubicin should not be administered in combination with taxanes in metastatic breast cancer patients relapsed after an anthracycline-based adjuvant or neoadjuvant therapy. PMID:16622454

  10. Effects of resistance exercise on fatigue and quality of life in breast cancer patients undergoing adjuvant chemotherapy: A randomized controlled trial.

    PubMed

    Schmidt, Martina E; Wiskemann, Joachim; Armbrust, Petra; Schneeweiss, Andreas; Ulrich, Cornelia M; Steindorf, Karen

    2015-07-15

    Multiple exercise interventions have shown beneficial effects on fatigue and quality of life (QoL) in cancer patients, but various psychosocial interventions as well. It is unclear to what extent the observed effects of exercise interventions are based on physical adaptations or rather on psychosocial factors associated with supervised, group-based programs. It needs to be determined which aspects of exercise programs are truly effective. Therefore, we aimed to investigate whether resistance exercise during chemotherapy provides benefits on fatigue and QoL beyond potential psychosocial effects of group-based interventions. One-hundred-one breast cancer patients starting chemotherapy were randomly assigned to resistance exercise (EX) or a relaxation control (RC) group. Both interventions were supervised, group-based, 2/week over 12 weeks. The primary endpoint fatigue was assessed with a 20-item multidimensional questionnaire, QoL with the EORTC QLQ-C30/BR23. Analyses of covariance for individual changes from baseline to Week 13 were calculated. In RC, total and physical fatigue worsened during chemotherapy, whereas EX showed no such impairments (between-group p = 0.098 and 0.052 overall, and p = 0.038 and 0.034 among patients without severe baseline depression). Differences regarding affective or cognitive fatigue were not significant. Benefits of EX were also seen to affect role and social function. Effect sizes were between 0.43 and 0.48. Explorative analyses indicated significant effect modification by thyroxin use (p-interaction = 0.044). In conclusion, resistance exercise appeared to mitigate physical fatigue and maintain QoL during chemotherapy beyond psychosocial effects inherent to supervised group-based settings. Thus, resistance exercise could be an integral part of supportive care for breast cancer patients undergoing chemotherapy. PMID:25484317

  11. The role of surgical margins in treatment of Ewing's sarcoma family tumors: Experience of a single institution with 512 patients treated with adjuvant and neoadjuvant chemotherapy

    SciTech Connect

    Bacci, Gaetano . E-mail: gaetano.bacci@ior.it; Longhi, Alessandra; Briccoli, Antonio; Bertoni, Franco; Versari, Michela; Picci, Piero

    2006-07-01

    Purpose: To evaluate the importance of surgical margins for local and systemic control of Ewing's sarcoma family tumors (ESFT). Methods and Materials: Between 1979 and 1999, 512 patients with ESFTs entered 4 different adjuvant and neoadjuvant studies performed at a single institution. Of these patients, 335 were treated with surgery alone (196) or surgery followed by radiotherapy at doses of 44.8 Gy (139). We compared their outcome with that of the 177 patients who were locally treated by radiotherapy at 60 Gy. Results: Local control (88.8% vs. 80.2%, p < 0.009) and 5-year disease-free survival (63.8% vs. 47.6%, p < 0.0007) were significantly better in patients treated with surgery and, among them, in those with adequate surgical margins (96.6% vs. 71,7%, p < 0.0008, and 69.6% vs. 46.3%, p < 0.0002). Nonetheless, better results were observed only in extremity tumors. Conclusions: Surgery is better than radiotherapy in cases of extremity ESFT with achievable adequate surgical margins, and in cases of inadequate surgical margins, adjuvant reduced-dose radiotherapy is ineffective. Therefore, when inadequate margins are expected, patients are better treated with full-dose radiotherapy from the start.

  12. Esophageal Metastasis to the Iris Effectively Palliated Using Stereotactic Body Radiation Therapy and Adjuvant Intravitreal Chemotherapy: Case Report and Literature Review

    PubMed Central

    Dhakal, Sughosh; Lema, Gareth M.C.; DiLoreto, David A.; Katz, Alan W.

    2012-01-01

    We report a case of isolated iris metastasis from esophageal adenocarcinoma that was successfully managed with local application of stereotactic body radiation therapy (SBRT) and adjunctive intravitreal therapy. A 53-year-old man with locally advanced esophageal adenocarcinoma achieved a complete clinical and radiographic response after surgery and chemotherapy. Four months later, he developed headache and decreased vision and was diagnosed with metastasis to the iris by slit-lamp examination. The decrease in vision was secondary to cystoid macular edema. The metastatic tumor and the patient's symptoms resolved after treatment with SBRT and intravitreal injections of bevacizumab and triamcinolone. We conclude that SBRT combined with intravitreal chemotherapy is an effective and well-tolerated palliative treatment for metastasis of esophageal adenocarcinoma to the iris. PMID:23275779

  13. Regorafenib as a potential adjuvant chemotherapy agent in disseminated small colon cancer: Drug selection outcome of a novel screening system using nanoimprinting 3-dimensional culture with HCT116-RFP cells.

    PubMed

    Yoshii, Yukie; Furukawa, Takako; Aoyama, Hironori; Adachi, Naoya; Zhang, Ming-Rong; Wakizaka, Hidekatsu; Fujibayashi, Yasuhisa; Saga, Tsuneo

    2016-04-01

    Colon cancer is one of the leading causes of cancer death worldwide. Adjuvant chemotherapy following primary surgical treatment is suggested to be beneficial in eradicating invisible disseminated small tumors in colon cancer; however, an effective drug remains to be developed. Recently, we reported a novel drug screening system using a nanoimprinting 3-dimensional (3D) culture that creates multicellular spheroids, which simulate in vivo conditions and, thereby, predict effective drugs in vivo. This study aimed to perform drug selection using our recently developed 3D culture system in a human colon cancer HCT116 cell line stably expressing red fluorescent protein (HCT116-RFP), to determine the most effective agent in a selection of clinically used antitumor agents for colon cancer. In addition, we confirmed the efficacy of the selected drug regorafenib, in vivo using a mouse model of disseminated small tumors. HCT116-RFP cells were cultured using a nanoimprinting 3D culture and in vitro drug selection was performed with 8 clinically used drugs [bevacizumab, capecitabine, cetuximab, 5-fluorouracil (5-FU), irinotecan, oxaliplatin, panitumumab and regorafenib]. An in vivo study was performed in mice bearing HCT116-RFP intraperitoneally disseminated small tumors using 3'-[18F]-fluoro-3'-deoxythymidine-positron emission tomography and fluorescence microscopy imaging to evaluate the therapeutic effects. Regorafenib was determined to be the most effective drug in the 3D culture, and significantly inhibited tumor growth in vivo, compared to the untreated control and 5-FU-treated group. The drug 5-FU is commonly used in colon cancer treatment and was used as a reference. Our results demonstrate that regorafenib is a potentially efficacious adjuvant chemotherapeutic agent for the treatment of disseminated small colon cancer and, therefore, warrants further preclinical and clinical studies. PMID:26820693

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

    PubMed

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

    2016-03-01

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

  15. Synergistic effects of laser and adjuvant therapies for cancer: progress in the development of novel cancer treatment methods using combinations of photothermal, photochemical, immunotherapy, and chemotherapy

    NASA Astrophysics Data System (ADS)

    Chen, Wei R.; Bartels, Kenneth E.; Korbelik, Mladen; Liu, Hong; Nordquist, Robert E.

    2005-04-01

    Combination therapy has been commonly used in chemotherapy, taking advantage of different effects of different chemotherapeutic agents. The treatment effects are often synergistic. The same approach has been investigated in laser phototherapy. Specifically, different combinations of laser photothermal interaction, laser photochemical interaction, immunotherapy and chemotherapy have been used in the treatment of tumors. These novel approaches showed promise in cancer treatment, particularly against metastatic tumors. The recent development in this area is discussed in this paper. Furthermore, a specific combination of photodynamic therapy (PDT) with a novel immunoadjuvant, glycated chitosan (GC), has shown to be effective in the treatment mammary tumors and lung tumors in mice. In the treatment of EMT6 tumor-bearing mice, the Photofrin-based PDT and GC has significantly increased the survival rates from 37.5% with PDT alone to 62.5% when a 0.1-ml 0.5% GC was peritumoral injected immediately after PDT treatment. The survival rate was further increased to 75.0% when GC of higher concentration was used. In comparison, the individual components of the PDT-GC treatment showed either no effect or very limited effects. In the treatment of a poorly immunogenic tumor model, Line 1 lung tumors in mice, the combination of PDT and GC resulted in a 37.5% survival rate, while no survival mice were observed with PDT alone.

  16. Sequencing postoperative radiotherapy and adjuvant chemotherapy in non-small cell lung cancer: unanswered questions on the not evidence-based approach.

    PubMed

    Kepka, Lucyna; Socha, Joanna; Rucinska, Monika; Wasilewska-Tesluk, Ewa; Komosinska, Katarzyna

    2016-07-01

    This editorial comments on the study by Lee et al. which reported on the use of postoperative radiotherapy (PORT) as first strategy after resection of stage IIIA-pN2 non-small cell lung cancer (NSCLC). After completion of PORT, 41% of patients received postoperative chemotherapy (POCT). The five-year overall survival (OS) was significantly higher in patients treated with PORT and POCT than in patients treated with PORT alone. Authors concluded that PORT used as first postoperative strategy does not compromise a benefit of POCT and its implementation should be further studied. We discuss the pros and cons of using PORT before POCT for stage IIIA-pN2 NSCLC. Some radiobiological data support earlier use of PORT, however, caution should be paid to not to unnecessarily delay or omit POCT because of its demonstrated survival benefit. Concurrent postoperative radio-chemotherapy could be an attractive approach, but we still have very limited clinical data on its use in this indication. PMID:27501290

  17. Sequencing postoperative radiotherapy and adjuvant chemotherapy in non-small cell lung cancer: unanswered questions on the not evidence-based approach

    PubMed Central

    Socha, Joanna; Rucinska, Monika; Wasilewska-Tesluk, Ewa; Komosinska, Katarzyna

    2016-01-01

    This editorial comments on the study by Lee et al. which reported on the use of postoperative radiotherapy (PORT) as first strategy after resection of stage IIIA-pN2 non-small cell lung cancer (NSCLC). After completion of PORT, 41% of patients received postoperative chemotherapy (POCT). The five-year overall survival (OS) was significantly higher in patients treated with PORT and POCT than in patients treated with PORT alone. Authors concluded that PORT used as first postoperative strategy does not compromise a benefit of POCT and its implementation should be further studied. We discuss the pros and cons of using PORT before POCT for stage IIIA-pN2 NSCLC. Some radiobiological data support earlier use of PORT, however, caution should be paid to not to unnecessarily delay or omit POCT because of its demonstrated survival benefit. Concurrent postoperative radio-chemotherapy could be an attractive approach, but we still have very limited clinical data on its use in this indication. PMID:27501290

  18. A Model to Estimate the Risk of Breast Cancer-Related Lymphedema: Combinations of Treatment-Related Factors of the Number of Dissected Axillary Nodes, Adjuvant Chemotherapy, and Radiation Therapy

    SciTech Connect

    Kim, Myungsoo; Kim, Seok Won; Lee, Sung Uk; Lee, Nam Kwon; Jung, So-Youn; Kim, Tae Hyun; Lee, Eun Sook; Kang, Han-Sung; Shin, Kyung Hwan

    2013-07-01

    Purpose: The development of breast cancer-related lymphedema (LE) is closely related to the number of dissected axillary lymph nodes (N-ALNs), chemotherapy, and radiation therapy. In this study, we attempted to estimate the risk of LE based on combinations of these treatment-related factors. Methods and Materials: A total of 772 patients with breast cancer, who underwent primary surgery with axillary lymph node dissection from 2004 to 2009, were retrospectively analyzed. Adjuvant chemotherapy (ACT) was performed in 677 patients (88%). Among patients who received radiation therapy (n=675), 274 (35%) received supraclavicular radiation therapy (SCRT). Results: At a median follow-up of 5.1 years (range, 3.0-8.3 years), 127 patients had developed LE. The overall 5-year cumulative incidence of LE was 17%. Among the 127 affected patients, LE occurred within 2 years after surgery in 97 (76%) and within 3 years in 115 (91%) patients. Multivariate analysis showed that N-ALN (hazard ratio [HR], 2.81; P<.001), ACT (HR, 4.14; P=.048), and SCRT (HR, 3.24; P<.001) were independent risk factors for LE. The total number of risk factors correlated well with the incidence of LE. Patients with no risk or 1 risk factor showed a significantly lower 5-year probability of LE (3%) than patients with 2 (19%) or 3 risk factors (38%) (P<.001). Conclusions: The risk factors associated with LE were N-ALN, ACT, and SCRT. A simple model using combinations of these factors may help clinicians predict the risk of LE.

  19. Thymidine phosphorylase mRNA expression may be a predictor of response to post-operative adjuvant chemotherapy with S-1 in patients with stage III colorectal cancer.

    PubMed

    Ogawa, Masaichi; Watanabe, Michiaki; Mitsuyama, Yoshinobu; Anan, Tadashi; Ohkuma, Masahisa; Kobayashi, Tetsuya; Eto, Ken; Yanaga, Katsuhiko

    2014-12-01

    The aim of the present study was to investigate markers in surgically resected specimens of colorectal cancer that can be used to predict the response to chemotherapy. The mRNA expression levels of enzymes involved in 5-fluorouracil (5-FU) metabolism and folate metabolism were measured in formalin-fixed, paraffin-embedded tumor sections obtained from the primary tumors of 54 patients with resected stage II or III colorectal cancer who received S-1 for one year. The 5-FU metabolizing enzymes studied were thymidylate synthase, dihydropyrimidine dehydrogenase and thymidine phosphorylase (TP). The folate metabolizing enzymes studied were folypolyglutamate synthetase, γ-glutamyl hydrolase and dihydrofolate reductase. The associations between the mRNA expression levels of these enzymes and clinical variables were investigated. Tumors were classified as exhibiting high or low expression as compared with the median mRNA expression level of each metabolizing enzyme defined as the cutoff value. The associations between the high and low expression levels of each enzyme and disease-free survival (DFS) were analyzed with the use of Kaplan-Meier curves and the log-rank test. DFS was not significantly associated with the relative mRNA expression level of any metabolizing enzyme in the study group as a whole, but there was a trend toward longer DFS in patients with high TP expression (P=0.066). In patients with stage III colorectal cancer, high TP expression was associated with significantly improved outcomes compared with low TP expression (P=0.039). These results indicate that the mRNA expression of TP, a metabolizing enzyme of 5-FU, is a significant predictor of response to post-operative chemotherapy with S-1 in patients with stage III colorectal cancer. PMID:25364408

  20. Id-1, Id-2, and Id-3 co-expression correlates with prognosis in stage I and II lung adenocarcinoma patients treated with surgery and adjuvant chemotherapy.

    PubMed

    Antonângelo, Leila; Tuma, Taila; Fabro, Alexandre; Acencio, Milena; Terra, Ricardo; Parra, Edwin; Vargas, Francisco; Takagaki, Teresa; Capelozzi, Vera

    2016-06-01

    Inhibitors of DNA binding/inhibitors of differentiation (Id) protein family have been shown to be involved in carcinogenesis. However, the roles of Id during lung adenocarcinoma (ADC) progression remain unclear. Eighty-eight ADC samples were evaluated for Id-1,2,3 level and angiogenesis (CD 34 and VEGF microvessel density) by immunohistochemistry and morphometry. The impact of these markers was tested on follow-up until death or recurrence. A significant difference between tumor and normal tissue was found for Id-1,2,3 expression (P < 0.01). In addition, high levels of nuclear Id-1 were associated with higher angiogenesis in the tumor stroma (P < 0.01). Equally significant was the association between patients in T1-stage and low cytoplasmic Id-2, as well as patients in stage-IIb and low Id-3. High cytoplasm Id-3 expression was also directly associated to lymph nodes metastasis (P = 0.05). Patients at stages I to III, with low Id-1 and Id-3 cytoplasm histoscores showed significant long metastasis-free survival time than those with high Id-1 or Id-3 expression (P = 0.04). Furthermore, high MVD-CD34 and MVD-VEGF expression were associated with short recurrence-free survival compared to low MVD-CD34 and MVD-VEGF expressions (P = 0.04). Cox model analyses controlled for age, lymph node metastasis, and adjuvant treatments showed that nuclear Id-1, cytoplasmic Id-3, and MVD-CD34 were significantly associated with survival time. Median score for nuclear Id-1 and cytoplasmic Id-3 divided patients in two groups, being that those with increased Id-1 and Id-3 presented higher risk of death. Ids showed an independent prognostic value in patients with lung ADC, regardless of disease stage. Id-1 and Id-3 should be considered new target candidates in the development of personalized therapy in lung ADC. PMID:26869608

  1. Aprepitant as prophylaxis of chemotherapy-induced nausea and vomiting in anthracyclines and cyclophosphamide-based regimen for adjuvant breast cancer.

    PubMed

    Meattini, Icro; Francolini, Giulio; Scotti, Vieri; De Luca Cardillo, Carla; Cappelli, Sabrina; Meacci, Fiammetta; Furfaro, Ilaria Francesca; Muntoni, Cristina; Scoccianti, Silvia; Detti, Beatrice; Mangoni, Monica; Nori, Jacopo; Orzalesi, Lorenzo; Fambrini, Massimiliano; Bianchi, Simonetta; Livi, Lorenzo

    2015-03-01

    The aim of our study was to evaluate the efficacy and safety of a three-drug antiemetic prophylaxis in a single-center series treated with anthracyclines and cyclophosphamide-based regimen for BC. We collected data from 92 consecutive patients treated with routine antiemetic prophylaxis consisted of aprepitant (oral 125 mg, on day 1; oral 80 mg, on days 2 and 3), a 5-HT3 receptor antagonist (palonosetron iv 0.25 mg, on day 1), and dexamethasone (iv 12 mg, on day 1). Acute and delayed phases were defined as the first 24 h and days 2-5 after treatment, respectively. Therapy outcomes were defined as complete response (CR), in case of no vomiting, no rescue treatment; complete protection (CP), in case of no vomiting, no rescue treatment, no significant nausea; and total control (TC), in case of no vomiting, no rescue treatment, no nausea. Overall, 89.1 and 81.5% of patients showed CR in acute and delayed phase, respectively; 67.4 and 62% showed CP in acute and delayed phase, respectively; and 52.2 and 48.9% of patients showed TC in acute and delayed phase, respectively. 4.3% complained an episode of emesis during the first 24 h from treatment, while in delayed phase, only 2.2% of patients had vomiting. Our analysis confirmed that a three-drug prophylaxis is safe, effective, and consequently highly recommended in patients who undergo anthracyclines and cyclophosphamide-based regimens, though still not classified as highly emetogenic chemotherapy by all the international guidelines. PMID:25698536

  2. Adjuvant treatment for pancreatic cancer.

    PubMed

    Daoud, Vladimir; Saif, Muhammad Wasif; Goodman, Martin

    2014-07-01

    Pancreatic cancer is the fourth leading cause of cancer deaths in both men and women. Surgical resection has been shown to be the only curable treatment available. Unfortunately only 20% of all patients diagnosed with pancreatic cancer are surgical candidates due to the aggressive biology of this disease. There is no clear consensus on what type of adjuvant therapy should be used for patients with pancreatic cancer. Chemoradiation is the favored treatment modality by many in the United States while gemcitabine based chemotherapy is favored in Europe. Both of these approaches have been shown by large prospective, randomized trials to improve disease free intervals and in some studies overall survival. The survival of these patients, even status post resection and adjuvant therapy, remains poor and therefore the need for alternative adjuvant therapies is needed. We will therefore discuss Abstracts #4124, #TPS4162, #4120 and #E15191 in this paper which are relevant to the issues described above. PMID:25076340

  3. Failure to Adhere to Protocol Specified Radiation Therapy Guidelines Was Associated With Decreased Survival in RTOG 9704-A Phase III Trial of Adjuvant Chemotherapy and Chemoradiotherapy for Patients With Resected Adenocarcinoma of the Pancreas

    SciTech Connect

    Abrams, Ross A.; Winter, Kathryn A.; Regine, William F.; Safran, Howard; Hoffman, John P.; Lustig, Robert; Konski, Andre A.; Benson, Al B.; Macdonald, John S.; Rich, Tyvin A.; Willett, Christopher G.

    2012-02-01

    Purpose: In Radiation Therapy Oncology Group 9704, as previously published, patients with resected pancreatic adenocarcinoma received continuous infusion 5-FU and concurrent radiotherapy (5FU-RT). 5FU-RT treatment was preceded and followed by randomly assigned chemotherapy, either 5-FU or gemcitabine. This analysis explored whether failure to adhere to specified RT guidelines influenced survival and/or toxicity. Methods and Materials: RT requirements were protocol specified. Adherence was scored as per protocol (PP) or less than per protocol (adjuvant protocol for pancreatic adenocarcinoma to evaluate the impact of adherence to specified RT protocol guidelines on protocol outcomes. Failure to adhere to specified RT guidelines was associated with reduced survival and, for patients receiving gemcitabine, trend toward increased nonhematologic toxicity.

  4. Impact of Lymph Node Ratio on Oncologic Outcomes in ypStage III Rectal Cancer Patients Treated with Neoadjuvant Chemoradiotherapy followed by Total Mesorectal Excision, and Postoperative Adjuvant Chemotherapy

    PubMed Central

    Kim, Jae-Sung; Kim, Kyubo; Chie, Eui Kyu; Kang, Sung-Bum; Lee, Keun-Wook; Kim, Jee Hyun; Jeong, Seung-Yong; Kim, Tae-You

    2015-01-01

    Purpose To evaluate the prognostic impact of the lymph node ratio (LNR) in ypStage III rectal cancer patients who were treated with neoadjuvant chemoradiotherapy (NCRT). Materials and Methods We retrospectively reviewed the data of 638 consecutive patients who underwent NCRT followed by total mesorectal excision, and postoperative adjuvant chemotherapy for rectal cancer from 2004 to 2011. Of these, 125 patients were positive for lymph node (LN) metastasis and were analyzed in this study. Results The median numbers of examined and metastatic LNs were 17 and 2, respectively, and the median LNR was 0.143 (range, 0.02–1). Median follow-up time was 55 months. In multivariate analyses, LNR was an independent prognostic factor for overall survival (OS) (hazard ratio [HR] 2.17, p = 0.041), disease-free survival (DFS) (HR 2.28, p = 0.005), and distant metastasis-free survival (DMFS) (HR 2.30, p = 0.010). When ypN1 patients were divided into low (low LNR ypN1 group) and high LNR (high LNR ypN1 group) according to a cut-off value of 0.152, the high LNR ypN1 group had poorer OS (p = 0.043) and DFS (p = 0.056) compared with the low LNR ypN1 group. And there were no differences between the high LNR ypN1 group and the ypN2 group in terms of the OS (p = 0.703) and DFS (p = 0.831). Conclusions For ypN-positive rectal cancer patients, the LNR was a more effective prognostic marker than the ypN stage, circumferential resection margin, or tumor regression grade after NCRT, and could be used to discern the high-risk group among ypN1 patients. PMID:26381522

  5. Chemotherapy in metastatic retinoblastoma.

    PubMed

    Kingston, J E; Hungerford, J L; Plowman, P N

    1987-03-01

    Eleven children with metastatic retinoblastoma diagnosed during the period 1970-1984 were treated with chemotherapy. Short-term complete responses were observed in three children treated with a four-drug combination which included cisplatinum, and in one child treated with vincristine and cyclophosphamide. The median duration of survival of the 11 children receiving chemotherapy was nine months, whilst the median survival of 13 children with metastatic retinoblastoma who were not given chemotherapy was only 2.3 months (p = 0.06). This suggests that retinoblastoma is a chemosensitive tumour and therefore adjuvant chemotherapy may have a role in children with retinoblastoma who at diagnosis are thought to be at high risk of developing metastatic disease. PMID:3587892

  6. Chemotherapy for Stage II Colon Cancer.

    PubMed

    Varghese, Anna

    2015-12-01

    The adjuvant treatment of patients with stage II colon cancer is an area of controversy in medical oncology. Adjuvant chemotherapy aims to eradicate micrometastatic disease present at the time of surgery, preventing the development of distant metastatic disease and thereby curing those patients of their cancer. National and international guidelines for the adjuvant treatment of stage II colon cancer recommend a range of treatment options from observation to chemotherapy with single-agent or combination regimens, depending on the presence or absence of high-risk features (poorly differentiated histology, presence of lymphovascular invasion, presence of perineural invasion, report of < 12 lymph nodes, bowel obstruction, localized perforation, or positive margins). In the one prospective study designed to address the role of adjuvant chemotherapy in stage II colon cancer, a small but statistically significant benefit in overall survival was seen for those patients who received adjuvant chemotherapy; however, multiple meta-analyses and retrospective subgroup analyses have called these findings into question. Though there may be a role for adjuvant chemotherapy in the treatment of patients with stage II colon cancer, its incremental benefit is small, at best, and comes with the risks of real and rarely fatal complications of chemotherapy. PMID:26648796

  7. Pooled Analysis of the Prognostic and Predictive Effects of KRAS Mutation Status and KRAS Mutation Subtype in Early-Stage Resected Non–Small-Cell Lung Cancer in Four Trials of Adjuvant Chemotherapy

    PubMed Central

    Shepherd, Frances A.; Domerg, Caroline; Hainaut, Pierre; Jänne, Pasi A.; Pignon, Jean-Pierre; Graziano, Stephen; Douillard, Jean-Yves; Brambilla, Elizabeth; Le Chevalier, Thierry; Seymour, Lesley; Bourredjem, Abderrahmane; Teuff, Gwénaël Le; Pirker, Robert; Filipits, Martin; Rosell, Rafael; Kratzke, Robert; Bandarchi, Bizhan; Ma, Xiaoli; Capelletti, Marzia; Soria, Jean-Charles; Tsao, Ming-Sound

    2013-01-01

    Purpose We undertook this analysis of KRAS mutation in four trials of adjuvant chemotherapy (ACT) versus observation (OBS) to clarify the prognostic/predictive roles of KRAS in non–small-cell lung cancer (NSCLC). Methods KRAS mutation was determined in blinded fashion. Exploratory analyses were performed to characterize relationships between mutation status and subtype and survival outcomes using a multivariable Cox model. Results Among 1,543 patients (763 OBS, 780 ACT), 300 had KRAS mutations (codon 12, n = 275; codon 13, n = 24; codon 14, n = 1). In OBS patients, there was no prognostic difference for overall survival for codon-12 (mutation v wild type [WT] hazard ratio [HR] = 1.04; 95% CI, 0.77 to 1.40) or codon-13 (HR = 1.01; 95% CI, 0.47 to 2.17) mutations. No significant benefit from ACT was observed for WT-KRAS (ACT v OBS HR = 0.89; 95% CI, 0.76 to 1.04; P = .15) or codon-12 mutations (HR = 0.95; 95% CI, 0.67 to 1.35; P = .77); with codon-13 mutations, ACT was deleterious (HR = 5.78; 95% CI, 2.06 to 16.2; P < .001; interaction P = .002). There was no prognostic effect for specific codon-12 amino acid substitution. The effect of ACT was variable among patients with codon-12 mutations: G12A or G12R (HR = 0.66; P = .48), G12C or G12V (HR = 0.94; P = .77) and G12D or G12S (HR = 1.39; P = .48; comparison of four HRs, including WT, interaction P = .76). OBS patients with KRAS-mutated tumors were more likely to develop second primary cancers (HR = 2.76, 95% CI, 1.34 to 5.70; P = .005) but not ACT patients (HR = 0.66; 95% CI, 0.25 to 1.75; P = .40; interaction, P = .02). Conclusion KRAS mutation status is not significantly prognostic. The potential interaction in patients with codon-13 mutations requires validation. At this time, KRAS status cannot be recommended to select patients with NSCLC for ACT. PMID:23630215

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

    PubMed Central

    2014-01-01

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

  9. Current adjuvant treatment modalities for gastric cancer: From history to the future.

    PubMed

    Kilic, Leyla; Ordu, Cetin; Yildiz, Ibrahim; Sen, Fatma; Keskin, Serkan; Ciftci, Rumeysa; Pilanci, Kezban Nur

    2016-05-15

    The discrepancy between the surgical technique and the type of adjuvant chemotherapy used in clinical trials and patient outcomes in terms of overall survival rates has led to the generation of different adjuvant treatment protocols in distinct parts of the world. The adjuvant treatment recommendation is generally chemoradiotherapy in the United States, perioperative chemotherapy in the United Kingdom and parts of Europe, and chemotherapy in Asia. These options mainly rely on the United States Intergroup-0116, United Kingdom British Medical Research Council Adjuvant Gastric Infusional Chemotherapy, and the Asian Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer and Capecitabine and Oxaliplatin Adjuvant Study in Stomach Cancer trials. However, the benefits were evident for only certain patients, which were not very homogeneous regarding the type of surgery, chemotherapy regimens, and stage of disease. Whether the dissimilarities in survival are attributable to surgical technique or intrinsic biological differences is a subject of debate. Regardless of the extent of surgery, multimodal therapy may offer modest survival advantage at least for diseases with lymph node involvement. Moreover, in the era of individualized treatment for most of the other cancer types, identification of special subgroups comprising those who will derive more or no benefit from adjuvant therapy merits further investigation. The aim of this review is to reveal the historical evolution and future reflections of adjuvant treatment modalities for resected gastric cancer patients. PMID:27190583

  10. Current adjuvant treatment modalities for gastric cancer: From history to the future

    PubMed Central

    Kilic, Leyla; Ordu, Cetin; Yildiz, Ibrahim; Sen, Fatma; Keskin, Serkan; Ciftci, Rumeysa; Pilanci, Kezban Nur

    2016-01-01

    The discrepancy between the surgical technique and the type of adjuvant chemotherapy used in clinical trials and patient outcomes in terms of overall survival rates has led to the generation of different adjuvant treatment protocols in distinct parts of the world. The adjuvant treatment recommendation is generally chemoradiotherapy in the United States, perioperative chemotherapy in the United Kingdom and parts of Europe, and chemotherapy in Asia. These options mainly rely on the United States Intergroup-0116, United Kingdom British Medical Research Council Adjuvant Gastric Infusional Chemotherapy, and the Asian Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer and Capecitabine and Oxaliplatin Adjuvant Study in Stomach Cancer trials. However, the benefits were evident for only certain patients, which were not very homogeneous regarding the type of surgery, chemotherapy regimens, and stage of disease. Whether the dissimilarities in survival are attributable to surgical technique or intrinsic biological differences is a subject of debate. Regardless of the extent of surgery, multimodal therapy may offer modest survival advantage at least for diseases with lymph node involvement. Moreover, in the era of individualized treatment for most of the other cancer types, identification of special subgroups comprising those who will derive more or no benefit from adjuvant therapy merits further investigation. The aim of this review is to reveal the historical evolution and future reflections of adjuvant treatment modalities for resected gastric cancer patients. PMID:27190583

  11. Adjuvant therapy for ampullary carcinomas: The Mayo Clinic experience

    SciTech Connect

    Bhatia, Sumita; Miller, Robert C. . E-mail: miller.robert@mayo.edu; Haddock, Michael G.; Donohue, John H.; Krishnan, Sunil

    2006-10-01

    Purpose: To determine the effects of adjuvant radiotherapy and chemotherapy for carcinoma of the ampulla of Vater. Methods and Materials: We retrospectively reviewed the records of 125 patients who underwent definitive surgery for carcinomas involving the ampulla of Vater between April 1977 and February 2005 and who survived more than 50 days after surgery. Twenty-nine of the patients also received adjuvant radiotherapy (median dose, 50.4 Gy in 28 fractions) with concurrent 5-fluorouracil chemotherapy. Adverse prognostic factors were investigated, and overall survival (OS) and local and distant failure were estimated. Results: Adverse prognostic factors for decreased OS by univariate analysis included lymph node (LN) involvement, locally advanced tumors (T3/T4), and poor histologic grade. By multivariate analysis, positive LN status (p = 0.02) alone was associated with decreased OS. The addition of adjuvant radiotherapy and chemotherapy improved OS for patients with positive LN (p = 0.01). Median survival for positive LN patients receiving adjuvant therapy was 3.4 years, vs. 1.6 years for those with surgery alone. Conclusions: The addition of adjuvant radiotherapy and 5-fluorouracil chemotherapy may improve OS in patients with LN involvement. The effect of adjuvant therapy on outcomes for patients with poor histologic grade or T3/T4 tumors without LN involvement could not be assessed.

  12. FAM20A binds to and regulates FAM20C localization

    PubMed Central

    Ohyama, Yoshio; Lin, Ju-Hsien; Govitvattana, Nattanan; Lin, I-Ping; Venkitapathi, Sundharamani; Alamoudi, Ahmed; Husein, Dina; An, Chunying; Hotta, Hak; Kaku, Masaru; Mochida, Yoshiyuki

    2016-01-01

    Mutations in the Family with sequence similarity (FAM) 20 gene family are associated with mineralized tissue phenotypes in humans. Among these genes, FAM20A mutations are associated with Amelogenesis Imperfecta (AI) with gingival hyperplasia and nephrocalcinosis, while FAM20C mutations cause Raine syndrome, exhibiting bone and craniofacial/dental abnormalities. Although it has been demonstrated that Raine syndrome associated-FAM20C mutants prevented FAM20C kinase activity and secretion, overexpression of the catalytically inactive D478A FAM20C mutant was detected in both cell extracts and the media. This suggests that FAM20C secretion doesn’t require its kinase activity, and that another molecule(s) may control the secretion. In this study, we found that extracellular FAM20C localization was increased when wild-type (WT), but not AI-forms of FAM20A was co-transfected. On the other hand, extracellular FAM20C was absent in the conditioned media of mouse embryonic fibroblasts (MEFs) derived from Fam20a knock-out (KO) mouse, while it was detected in the media from WT MEFs. We also showed that cells with the conditioned media of Fam20a WT MEFs mineralized, but those with the conditioned media of KO MEFs failed to mineralize in vitro. Our data thus demonstrate that FAM20A controls FAM20C localization that may assist in the extracellular function of FAM20C in mineralized tissues. PMID:27292199

  13. Adjuvant therapy for gastric cancer: Current and future directions

    PubMed Central

    Foo, Marcus; Leong, Trevor

    2014-01-01

    The management of gastric cancer continues to evolve. Whilst surgery alone is effective when tumours present early, a large proportion of patients are diagnosed with loco-regionally advanced disease, resulting in high loco-regional and distant relapse rates, with subsequent poor survival. Early attempts at improving outcomes following resection were disappointing; however, randomized trials have now established either post-operative chemoradiotherapy (INT0116) or peri-operative chemotherapy as standard adjuvant therapies in the Western world. There remain, however, significant differences in the approach to management between the West and East. In Asia, where there is the highest incidence of gastric cancer, extended resection followed by adjuvant chemotherapy represents the standard of care. This review discusses current standard adjuvant therapy in gastric adenocarcinoma, as well as recent and ongoing trials investigating novel (neo)adjuvant approaches, which hope to build on the successes of previous studies. PMID:25320509

  14. Is adjuvant chemotherapy of benefit for postmenopausal women who receive endocrine treatment for highly endocrine-responsive, node-positive breast cancer? International Breast Cancer Study Group Trials VII and 12-93.

    PubMed

    Pagani, Olivia; Gelber, Shari; Simoncini, Edda; Castiglione-Gertsch, Monica; Price, Karen N; Gelber, Richard D; Holmberg, Stig B; Crivellari, Diana; Collins, John; Lindtner, Jurij; Thürlimann, Beat; Fey, Martin F; Murray, Elizabeth; Forbes, John F; Coates, Alan S; Goldhirsch, Aron

    2009-08-01

    To compare the efficacy of chemoendocrine treatment with that of endocrine treatment (ET) alone for postmenopausal women with highly endocrine responsive breast cancer. In the International Breast Cancer Study Group (IBCSG) Trials VII and 12-93, postmenopausal women with node-positive, estrogen receptor (ER)-positive or ER-negative, operable breast cancer were randomized to receive either chemotherapy or endocrine therapy or combined chemoendocrine treatment. Results were analyzed overall in the cohort of 893 patients with endocrine-responsive disease, and according to prospectively defined categories of ER, age and nodal status. STEPP analyses assessed chemotherapy effect. The median follow-up was 13 years. Adding chemotherapy reduced the relative risk of a disease-free survival event by 19% (P = 0.02) compared with ET alone. STEPP analyses showed little effect of chemotherapy for tumors with high levels of ER expression (P = 0.07), or for the cohort with one positive node (P = 0.03). Chemotherapy significantly improves disease-free survival for postmenopausal women with endocrine-responsive breast cancer, but the magnitude of the effect is substantially attenuated if ER levels are high. PMID:18953651

  15. Adjuvant and neoadjuvant treatment in pancreatic cancer

    PubMed Central

    Herreros-Villanueva, Marta; Hijona, Elizabeth; Cosme, Angel; Bujanda, Luis

    2012-01-01

    Pancreatic adenocarcinoma is one of the most aggressive human malignancies, ranking 4th among causes for cancer-related death in the Western world including the United States. Surgical resection offers the only chance of cure, but only 15 to 20 percent of cases are potentially resectable at presentation. Different studies demonstrate and confirm that advanced pancreatic cancer is among the most complex cancers to treat and that these tumors are relatively resistant to chemotherapy and radiotherapy. Currently there is no consensus around the world on what constitutes “standard” adjuvant therapy for pancreatic cancer. This controversy derives from several studies, each fraught with its own limitations. Standards of care also vary somewhat with regard to geography and economy, for instance chemo-radiotherapy followed by chemotherapy or vice versa is considered the optimal therapy in North America while chemotherapy alone is the current standard in Europe. Regardless of the efforts in adjuvant and neoadjuvant improved therapy, the major goal to combat pancreatic cancer is to find diagnostic markers, identifying the disease in a pre-metastatic stage and making a curative treatment accessible to more patients. In this review, authors examined the different therapy options for advanced pancreatic patients in recent years and the future directions in adjuvant and neoadjuvant treatments for these patients. PMID:22529684

  16. Cancer Chemotherapy

    MedlinePlus

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

  17. Cancer Chemotherapy

    MedlinePlus

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

  18. Systemic adjuvant therapies in renal cell carcinoma.

    PubMed

    Buti, Sebastiano; Bersanelli, Melissa; Donini, Maddalena; Ardizzoni, Andrea

    2012-10-01

    Renal cell carcinoma (RCC) is one of the ten most frequent solid tumors worldwide. Recent innovations in the treatment of metastatic disease have led to new therapeutic approaches being investigated in the adjuvant setting. Observation is the only current standard of care after radical nephrectomy, although there is evidence of efficacy of adjuvant use of vaccine among all the strategies used. This article aims to collect published experiences with systemic adjuvant approaches in RCC and to describe the results of past and ongoing phase III clinical trials in this field. We explored all the systemic treatments, including chemotherapy, immunotherapy and targeted drugs while alternative approaches have also been described. Appropriate selection of patients who would benefit from adjuvant therapies remains a crucial dilemma. Although the international guidelines do not actually recommend any adjuvant treatment after radical surgery for RCC, no conclusions have yet been drawn pending the results of the promising ongoing clinical trials with the target therapies. The significant changes that these new drugs have made on advanced disease outcome could represent the key to innovation in terms of preventing recurrence, delaying relapse and prolonging survival after radical surgery for RCC. PMID:25992216

  19. Neo-adjuvant capecitabine chemotherapy in women with newly diagnosed locally advanced breast cancer in a resource-poor setting (Nigeria): efficacy and safety in a phase II feasibility study.

    PubMed

    Arowolo, Olukayode A; Njiaju, Uchenna O; Ogundiran, Temidayo O; Abidoye, Oyewale; Lawal, Olukayode O; Obajimi, Millicent; Adetiloye, Adebayo V; Im, Hae K; Akinkuolie, Akinbolaji A; Oluwasola, Abideen; Adelusola, Kayode; Kayode, Adesunkanmi A; Agbakwuru, Augustine E; Oduntan, Helen; Babalola, Chinedum P; Fleming, Gini; Olopade, Olusola C; Falusi, Adeyinka Gladys; Durosinmi, Muheez A; Olopade, Olufunmilayo I

    2013-01-01

    The majority of clinical trials of neo-adjuvant therapy for breast cancer have been conducted in resource-rich countries. We chose Nigeria, a resource-poor country, as the major site for a phase II feasibility open-label multicenter clinical trial designed to evaluate the efficacy, safety, and tolerability of neo-adjuvant capecitabine in locally advanced breast cancer (LABC). Planned treatment consisted of 24 weeks of capecitabine at a dose of 1,000 mg/m(2) twice daily (2,000 mg/m(2) total per day). The primary endpoints were overall, partial, complete clinical response rate (OCR, PCR, CCR) and complete pathologic response (cPR). A total of 16 patients were recruited from August 2007 to April 2010. The study was terminated early as a result of slow accrual. After the first three cycles of therapy, PCR were seen in five of 16 patients (31%; 95% CI 11-59%). Of the remaining 11 patients, eight had no response (NR) or stable disease (SD), and three had progressive disease (PD). Seven patients proceeded with further therapy of which had SD. OCR at the end of eight cycles was 44% (95% CI 20-70%). Clinical response and radiologic response by ultrasonomammography were highly concordant (spearman correlation 0.70). The most common adverse effect was Grade 1 hand-foot syndrome, which was seen in 75% of patients. Despite several limitations, we successfully carried out this phase II feasibility study of neo-adjuvant capecitabine for LABC in Nigeria. Capecitabine monotherapy showed good overall response rates with minimal toxicity and further studies are warranted. PMID:23865786

  20. Neo-adjuvant Capecitabine Chemotherapy in Women with Newly Diagnosed Locally Advanced Breast Cancer in a Resource-poor Setting (Nigeria): Efficacy and Safety in a Phase II Feasibility Study

    PubMed Central

    Arowolo, Olukayode A; Njiaju, Uchenna O; Ogundiran, Temidayo O; Abidoye, Oyewale; Lawal, Olukayode O; Obajimi, Millicent; Adetiloye, Adebayo V; Im, Hae K; Akinkuolie, Akinbolaji A; Oluwasola, Abideen; Adelusola, Kayode; Kayode, Adesunkanmi A; Agbakwuru, Augustine E; Oduntan, Helen; Babalola, Chinedum P; Fleming, Gini; Olopade, Olusola C; Falusi, Adeyinka Gladys; Durosinmi, Muheez A; Olopade, Olufunmilayo I

    2013-01-01

    The majority of clinical trials of neo-adjuvant therapy for breast cancer have been conducted in resource-rich countries. We chose Nigeria, a resource-poor country, as the major site for a phase II feasibility open-label multicenter clinical trial designed to evaluate the efficacy, safety, and tolerability of neo-adjuvant capecitabine in locally advanced breast cancer (LABC). Planned treatment consisted of 24 weeks of capecitabine at a dose of 1,000 mg/m2 twice daily (2,000 mg/m2 total per day). The primary endpoints were overall, partial, complete clinical response rate (OCR, PCR, CCR) and complete pathologic response (cPR). A total of 16 patients were recruited from August 2007 to April 2010. The study was terminated early as a result of slow accrual. After the first three cycles of therapy, PCR were seen in five of 16 patients (31%; 95% CI 11–59%). Of the remaining 11 patients, eight had no response (NR) or stable disease (SD), and three had progressive disease (PD). Seven patients proceeded with further therapy of which had SD. OCR at the end of eight cycles was 44% (95% CI 20–70%). Clinical response and radiologic response by ultrasonomammography were highly concordant (spearman correlation 0.70). The most common adverse effect was Grade 1 hand–foot syndrome, which was seen in 75% of patients. Despite several limitations, we successfully carried out this phase II feasibility study of neo-adjuvant capecitabine for LABC in Nigeria. Capecitabine monotherapy showed good overall response rates with minimal toxicity and further studies are warranted. PMID:23865786

  1. [Prostate cancer and chemotherapy].

    PubMed

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

    2007-07-01

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

  2. Pathological complete response after neoadjuvant therapy for rectal cancer and the role of adjuvant therapy.

    PubMed

    Nelson, Valerie M; Benson, Al B

    2013-04-01

    Both the addition of neoadjuvant chemoradiation therapy and improvements in surgical techniques have improved local control and overall survival for locally advanced rectal cancer patients over the past few decades. The addition of adjuvant chemotherapy has likely improved outcomes as well, though the contribution has been more difficult to quantify. At present, the majority of resected locally advanced rectal cancer patients receive adjuvant chemotherapy, though there is great variability in this practice based on both patient and institution characteristics. Recently, questions have been raised regarding which sub-groups of patients benefit most from adjuvant chemotherapy. As pathologic complete response (pCR) is increasingly found to be a reasonable surrogate for long-term favorable outcomes, some have questioned the need for adjuvant therapy in this select group of patients. Multiple retrospective analyses have shown minimal to no benefit for adjuvant chemotherapy in this group. Indeed, the patients most consistently shown to benefit from adjuvant therapy both in terms of disease free survival (DFS) and overall survival (OS) are those who achieve an intermediate pathologic response to neoadjuvant treatment. Tumors that have high expression of thymidylate synthetase have also shown to benefit from adjuvant therapy. More study is needed into clinical and molecular features that predict patient benefit from adjuvant therapy. PMID:23381584

  3. Uncaria tomentosa-Adjuvant Treatment for Breast Cancer: Clinical Trial.

    PubMed

    Santos Araújo, Maria do Carmo; Farias, Iria Luiza; Gutierres, Jessie; Dalmora, Sergio L; Flores, Nélia; Farias, Julia; de Cruz, Ivana; Chiesa, Juarez; Morsch, Vera Maria; Chitolina Schetinger, Maria Rosa

    2012-01-01

    Breast cancer is the most frequent neoplasm affecting women worldwide. Some of the recommended treatments involve chemotherapy whose toxic effects include leukopenia and neutropenia. This study assessed the effectiveness of Uncaria tomentosa (Ut) in reducing the adverse effects of chemotherapy through a randomized clinical trial. Patients with Invasive Ductal Carcinoma-Stage II, who underwent a treatment regimen known as FAC (Fluorouracil, Doxorubicin, Cyclophosphamide), were divided into two groups: the UtCa received chemotherapy plus 300 mg dry Ut extract per day and the Ca group that only received chemotherapy and served as the control experiment. Blood samples were collected before each one of the six chemotherapy cycles and blood counts, immunological parameters, antioxidant enzymes, and oxidative stress were analyzed. Uncaria tomentosa reduced the neutropenia caused by chemotherapy and was also able to restore cellular DNA damage. We concluded that Ut is an effective adjuvant treatment for breast cancer. PMID:22811748

  4. Uncaria tomentosa—Adjuvant Treatment for Breast Cancer: Clinical Trial

    PubMed Central

    Santos Araújo, Maria do Carmo; Farias, Iria Luiza; Gutierres, Jessie; Dalmora, Sergio L.; Flores, Nélia; Farias, Julia; de Cruz, Ivana; Chiesa, Juarez; Morsch, Vera Maria; Chitolina Schetinger, Maria Rosa

    2012-01-01

    Breast cancer is the most frequent neoplasm affecting women worldwide. Some of the recommended treatments involve chemotherapy whose toxic effects include leukopenia and neutropenia. This study assessed the effectiveness of Uncaria tomentosa (Ut) in reducing the adverse effects of chemotherapy through a randomized clinical trial. Patients with Invasive Ductal Carcinoma—Stage II, who underwent a treatment regimen known as FAC (Fluorouracil, Doxorubicin, Cyclophosphamide), were divided into two groups: the UtCa received chemotherapy plus 300 mg dry Ut extract per day and the Ca group that only received chemotherapy and served as the control experiment. Blood samples were collected before each one of the six chemotherapy cycles and blood counts, immunological parameters, antioxidant enzymes, and oxidative stress were analyzed. Uncaria tomentosa reduced the neutropenia caused by chemotherapy and was also able to restore cellular DNA damage. We concluded that Ut is an effective adjuvant treatment for breast cancer. PMID:22811748

  5. Assessment of microtubule-associated protein (MAP)-Tau expression as a predictive and prognostic marker in TACT; a trial assessing substitution of sequential docetaxel for FEC as adjuvant chemotherapy for early breast cancer.

    PubMed

    Irshad, S; Gillett, C; Pinder, S E; A'hern, R P; Dowsett, M; Ellis, I O; Bartlett, J M S; Bliss, J M; Hanby, A; Johnston, S; Barrett-Lee, P; Ellis, P; Tutt, A

    2014-04-01

    The TACT trial is the largest study assessing the benefit of taxanes as part of adjuvant therapy for early breast cancer. The goal of this translational study was to clarify the predictive and prognostic value of Tau within the TACT trial. Tissue microarrays (TMA) were available from 3,610 patients. ER, PR, HER2 from the TACT trial and Tau protein expression was determined by immunohistochemistry on duplicate TMAs. Two parallel scoring systems were generated for Tau expression ('dichotomised' vs. 'combined' score). The positivity rate of Tau expression was 50 % in the trial population (n = 2,483). Tau expression correlated positively with ER (p < 0.001) and PR status (p < 0.001); but negatively with histological grade (p < 0.001) and HER2 status (p < 0.001). Analyses with either scoring systems for Tau expression demonstrated no significant interaction between Tau expression and efficacy of docetaxel. Contrary to the hypothesis that taxane benefit would be enriched in Tau negative/low patients, the only groups with a suggestion of a reduced event rate in the taxane group were the HER2-positive, Tau positive subgroups. Tau expression was seen to be a prognostic factor on univariate analysis associated with an improved DFS, independent of the treatment group (p < 0.001). It had no prognostic value in ER-negative tumours and the weak prognostic effect of Tau in ER-positive tumours (p = 0.02) diminished, when considering ER as an ordinal variable. On multivariable analyses, Tau had no prognostic value in either group. In addition, no significant interaction between Tau expression and benefit from docetaxel in patients within the PR-positive and negative subsets was seen. This is now the second large adjuvant study, and the first with quantitative analysis of ER and Tau expression, failing to show an association between Tau and taxane benefit with limited utility as a prognostic marker for Tau in ER-positive early breast cancer patients. PMID:24519386

  6. Trends in vaccine adjuvants.

    PubMed

    Schijns, Virgil E J C; Lavelle, Ed C

    2011-04-01

    Adjuvants are essential components of most clinically used vaccines. This is because the majority of nonliving vaccines are relatively poor inducers of adaptive immunity unless effective adjuvants are co-administered. Aluminum salts (alum) have been used as adjuvants with great success for almost a century and have been particularly effective at promoting protective humoral immunity. However, alum is not optimally effective for diseases where cell-mediated immunity is required for protection. Furthermore, adjuvants including oil-in-water emulsions have shown improved efficacy for avian influenza protection suggesting that even for diseases where humoral immunity can confer protection, there is scope for developing improved adjuvants. There have been major developments in antigen discovery over the past decade, which has accelerated the vaccine development process for new indications and this demands a new generation of adjuvants that can drive and specifically direct the desired immune responses. A number of systems are under investigation that combine different types of adjuvants into specific formulations with greater activity. Additionally, targeting of vaccines to specific immune cells shows great promise. In the case of cancer and chronic infectious diseases, it may be difficult to develop effective vaccines without blocking immune regulatory pathways, which impede cell-mediated responses. However, increased understanding of immunology and particularly the innate immune system is informing vaccine adjuvant research and consequently driving the development of novel and specifically directed vaccine adjuvant strategies. In this article we address the importance of adjuvants in vaccine development, the known mode of action of specific adjuvants and recent developments in this important field. PMID:21506650

  7. Phase III Multi-Institutional Trial of Adjuvant Chemotherapy With Paclitaxel, Estramustine, and Oral Etoposide Combined With Long-Term Androgen Suppression Therapy and Radiotherapy Versus Long-Term Androgen Suppression Plus Radiotherapy Alone for High-Risk Prostate Cancer: Preliminary Toxicity Analysis of RTOG 99-02

    SciTech Connect

    Rosenthal, Seth A. Bae, Kyoungwha; Pienta, Kenneth J.; Sobczak, Mark L.; Asbell, Sucha O.; Rajan, Raghu; Kerlin, Kevin J.; Michalski, Jeff M.; Sandler, Howard M.

    2009-03-01

    Purpose: Long-term androgen suppression plus radiotherapy (AS+RT) is standard treatment of high-risk prostate cancer. A randomized trial, Radiation Therapy Oncology Group trial 9902, was undertaken to determine whether adjuvant chemotherapy with paclitaxel, estramustine, and etoposide (TEE) plus AS+RT would improve disease outcomes with acceptable toxicity. Methods and Materials: High-risk (prostate-specific antigen 20-100 ng/mL and Gleason score {>=}7; or Stage T2 or greater, Gleason score 8, prostate-specific antigen level <100 ng/mL) nonmetastatic prostate cancer patients were randomized to AS+RT (Arm 1) vs. AS+RT plus four cycles of TEE (Arm 2). TEE was delivered 4 weeks after RT. AS continued for 2 years for both treatment arms. RT began after 8 weeks of AS began. Results: The Radiation Therapy Oncology Group 9902 trial opened January 11, 2000. Excess thromboembolic toxicity was noted, leading to study closure October 4, 2004. A total of 397 patients were accrued, and the data for 381 were analyzable. An acute and long-term toxicity analysis was performed. The worst overall toxicities during treatment were increased for Arm 2. Of the 192 patients, 136 (71%) on Arm 2 had RTOG Grade 3 or greater toxicity compared with 70 (37%) of 189 patients on Arm 1. Statistically significant increases in hematologic toxicity (p < 0.0001) and gastrointestinal toxicity (p = 0.017) but not genitourinary toxicity (p = 0.07) were noted during treatment. Two Grade 5 complications related to neutropenic infection occurred in Arm 2. Three cases of myelodysplasia/acute myelogenous leukemia were noted in Arm 2. At 2 and 3 years after therapy completion, excess long-term toxicity was not observed in Arm 2. Conclusion: TEE was associated with significantly increased toxicity during treatment. The toxicity profiles did not differ at 2 and 3 years after therapy. Toxicity is an important consideration in the design of trials using adjuvant chemotherapy for prostate cancer.

  8. A Phase 3 Trial of 2 Years of Androgen Suppression and Radiation Therapy With or Without Adjuvant Chemotherapy for High-Risk Prostate Cancer: Final Results of Radiation Therapy Oncology Group Phase 3 Randomized Trial NRG Oncology RTOG 9902

    SciTech Connect

    Rosenthal, Seth A.; Hunt, Daniel; Sartor, A. Oliver; Pienta, Kenneth J.; Gomella, Leonard; Grignon, David; Rajan, Raghu; Kerlin, Kevin J.; Jones, Christopher U.; Dobelbower, Michael; Shipley, William U.; Zeitzer, Kenneth; Hamstra, Daniel A.; Donavanik, Viroon; Rotman, Marvin; Hartford, Alan C.; Michalski, Jeffrey; Seider, Michael; Kim, Harold; and others

    2015-10-01

    Purpose: Long-term (LT) androgen suppression (AS) with radiation therapy (RT) is a standard treatment of high-risk, localized prostate cancer (PCa). Radiation Therapy Oncology Group 9902 was a randomized trial testing the hypothesis that adjuvant combination chemotherapy (CT) with paclitaxel, estramustine, and oral etoposide plus LT AS plus RT would improve overall survival (OS). Methods and Materials: Patients with high-risk PCa (prostate-specific antigen 20-100 ng/mL and Gleason score [GS] ≥7 or clinical stage ≥T2 and GS ≥8) were randomized to RT and AS (AS + RT) alone or with adjuvant CT (AS + RT + CT). CT was given as four 21-day cycles, delivered beginning 28 days after 70.2 Gy of RT. AS was given as luteinizing hormone-releasing hormone for 24 months, beginning 2 months before RT plus an oral antiandrogen for 4 months before and during RT. The study was designed based on a 6% improvement in OS from 79% to 85% at 5 years, with 90% power and a 2-sided alpha of 0.05. Results: A total of 397 patients (380 eligible) were randomized. The patients had high-risk PCa, 68% with GS 8 to 10 and 34% T3 to T4 tumors, and median prostate-specific antigen of 22.6 ng/mL. The median follow-up period was 9.2 years. The trial closed early because of excess thromboembolic toxicity in the CT arm. The 10-year results for all randomized patients revealed no significant difference between the AS + RT and AS + RT + CT arms in OS (65% vs 63%; P=.81), biochemical failure (58% vs 54%; P=.82), local progression (11% vs 7%; P=.09), distant metastases (16% vs 14%; P=.42), or disease-free survival (22% vs 26%; P=.61). Conclusions: NRG Oncology RTOG 9902 showed no significant differences in OS, biochemical failure, local progression, distant metastases, or disease-free survival with the addition of adjuvant CT to LT AS + RT. The trial results provide valuable data regarding the natural history of high-risk PCa treated with LT AS + RT and have implications for

  9. [Influenza vaccine and adjuvant].

    PubMed

    Nakayama, Tetsuo

    2011-01-01

    Adjuvant is originated from the Latin word "adjuvare" which means "help" in English to enhance the immunological responses when given together with antigens. The beginning of adjuvant was mineral oil which enhanced the immune response when it was given with inactivated Salmonella typhimurium. Aluminium salt was used to precipitate diphtheria toxoid and increased level of antibody response was demonstrated when administered with alum-precipitated antigens. Since 1930, aluminium salt has been used as DTaP (diphtheria-tetanus-acellular pertussis vaccine) adjuvant. Many candidates were tested for adjuvant activity but only aluminum salt is allowed to use for human vaccines. New adjuvant MF59, oil-in-water emulsion type, was developed for influenza vaccine for elderly (Fluad) and series of AS adjuvant are used for hepatitis B, pandemic flue, and human papiloma virus vaccines. Oil-adjuvanted influenza pandemic vaccines induced higher antibody response than alum-adjuvanted vaccine with higher incidence of adverse events, especially for local reactions. Alum-adjuvanted whole virion inactivated H5N1 vaccine was developed in Japan, and it induced relatively well immune responses in adults. When it applied for children, febrile reaction was noted in approximately 60% of the subjects, with higher antibodies. Recent investigation on innate immunity demonstrates that adjuvant activity is initiated from the stimulation on innate immunity and/or inflammasome, resulting in cytokine induction and antigen uptake by monocytes and macrophages. The probable reason for high incidence of febrile reaction should be investigated to develop a safe and effective influenza vaccine. PMID:22129866

  10. Postoperative adjuvant radiotherapy for patients with gastric adenocarcinoma.

    PubMed

    Lim, Do Hoon

    2012-12-01

    In gastric adenocarcinoma, high rates of loco-regional recurrences have been reported even after complete resection, and various studies have been tried to find the role of postoperative adjuvant therapy. Among them, Intergroup 0116 trial was a landmark trial, and demonstrated the definite survival benefit in adjuvant chemoradiotherapy, compared with surgery alone. However, the INT 0116 trial had major limitation for global acceptance of the INT 0116 regimen as an adjuvant treatment modality because of the limited lymph node dissection. Lately, several randomized studies that were performed to patients with D2-dissected gastric cancer were published. This review summarizes the data about patterns of failure after surgical resection and the earlier prospective studies, including INT 0116 study. Author will introduce the latest studies, including ARTIST trial and discuss whether external beam radiotherapy should be applied to patients receiving extended lymph node dissection and adjuvant chemotherapy. PMID:23346491

  11. Improving Systemic Chemotherapy for Bladder Cancer.

    PubMed

    Rose, Tracy L; Milowsky, Matthew I

    2016-05-01

    Systemic chemotherapy is integral to the management of muscle-invasive and metastatic bladder cancer (BCa). Neoadjuvant chemotherapy has been increasingly utilized for muscle-invasive BCa over the past several years, and several options for cisplatin-based regimens have emerged. Adjuvant chemotherapy may be considered for select patients who did not receive neoadjuvant therapy. Systemic chemotherapy added to radiotherapy is a critical component of a bladder-preserving approach and superior to radiotherapy alone. Cisplatin-based chemotherapy has been the mainstay for metastatic BCa for more than three decades. Novel targeted agents are in development fueled by the recent molecular characterization of BCa. Recent trials of immunotherapy have demonstrated the possibility of a less toxic and potentially more effective treatment for metastatic disease. It is an extremely exciting time for BCa research, and much needed improvements in systemic treatment are most certainly on the horizon. PMID:26984414

  12. Anticancer chemotherapy

    SciTech Connect

    Weller, R.E.

    1988-10-01

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

  13. Chemotherapy and Your Mouth

    MedlinePlus

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

  14. [Adjuvant drug therapies for breast cancer].

    PubMed

    Huovinen, Riikka; Auvinen, Päivi; Mattson, Johanna; Joensuu, Heikki

    2015-01-01

    Most breast cancers are hormone receptor positive and exhibit a slow growth pattern. Based on biological properties, breast cancers are divided into four different biological subtypes. Furthermore, these subtypes are indicative of the risk of recurrence, which is also influenced by the size of the tumor and extension to lymph nodes. Postoperative adjuvant drug therapy is chosen on the basis of the biological type. Chemotherapy can be used in all subtypes. Hormonal therapies are used exclusively for the treatment of hormone receptor positive breast cancer. Trastuzumab antibody belongs to the treatment of the HER2 positive subtype. PMID:26245052

  15. Update in Cancer Chemotherapy: Gastrointestinal Cancer—Colorectal Cancer, Part 2

    PubMed Central

    Wright, Jane C.

    1986-01-01

    An update of the state of the art of cancer chemotherapeutic treatment of gastrointestinal tract cancer is described in a multi-part series. Part 1 surveyed colorectal cancer and the use of single-agent chemotherapy in the April issue of the Journal. Part 2 of colorectal cancer will describe combination chemotherapy, preoperative and postoperative radiation, and combinations of chemotherapy and radiation, and adjuvant chemotherapy. In advanced gastrointestinal tract cancer, chemotherapy is only of palliative value with response rates generally under 50 percent and survival rates of several months to one year or more. Combination chemotherapy often produces higher response rates, yet there is no acceptable evidence that survival is improved. While some adjuvant chemotherapy trials suggest improvement, major survival gains remain to be demonstrated. Uncertainty as to the role of chemotherapy in the treatment of gastrointestinal cancers may be due to lack of data. PMID:3519988

  16. Who Benefits From Adjuvant Radiation Therapy for Gastric Cancer? A Meta-Analysis

    SciTech Connect

    Ohri, Nitin; Garg, Madhur K.; Aparo, Santiago; Kaubisch, Andreas; Tome, Wolfgang; Kennedy, Timothy J.; Kalnicki, Shalom; Guha, Chandan

    2013-06-01

    Purpose: Large randomized trials have demonstrated significant survival benefits with the use of adjuvant chemotherapy or chemoradiation therapy for gastric cancer. The importance of adjuvant radiation therapy (RT) remains unclear. We performed an up-to-date meta-analysis of randomized trials testing the use of RT for resectable gastric cancer. Methods and Materials: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized trials testing adjuvant (including neoadjuvant) RT for resectable gastric cancer. Hazard ratios describing the impact of adjuvant RT on overall survival (OS) and disease-free survival (DFS) were extracted directly from the original studies or calculated from survival curves. Pooled estimates were obtained using the inverse variance method. Subgroup analyses were performed to determine whether the efficacy of RT varies with chemotherapy use, RT timing, geographic region, type of nodal dissection performed, or lymph node status. Results: Thirteen studies met all inclusion criteria and were used for this analysis. Adjuvant RT was associated with a significant improvement in both OS (HR = 0.78, 95% CI: 0.70-0.86, P<.001) and DFS (HR = 0.71, 95% CI: 0.63-0.80, P<.001). In the 5 studies that tested adjuvant chemoradiation therapy against adjuvant chemotherapy, similar effects were seen for OS (HR = 0.83, 95% CI: 0.67-1.03, P=.087) and DFS (HR = 0.77, 95% CI: 0.91-0.65, P=.002). Available data did not reveal any subgroup of patients that does not benefit from adjuvant RT. Conclusion: In randomized trials for resectable gastric cancer, adjuvant RT provides an approximately 20% improvement in both DFS and OS. Available data do not reveal a subgroup of patients that does not benefit from adjuvant RT. Further study is required to optimize the implementation of adjuvant RT for gastric cancer with regard to patient selection and integration with systemic therapy.

  17. 26,26,26,27,27,27-Hexadeuterated-1,25-Dihydroxyvitamin D3 (1,25D-d6) As Adjuvant of Chemotherapy in Breast Cancer Cell Lines

    PubMed Central

    Seoane, Samuel; Bermudez, Maria A.; Sendon-Lago, Juan; Martinez-Ordoñez, Anxo; Abdul-Hadi, Soraya; Maestro, Miguel; Mouriño, Antonio; Perez-Fernandez, Roman

    2013-01-01

    It has been demonstrated that 1,25-dihydroxyvitamin D3 (1,25D) and some of its analogues have antitumor activity. 1,25D labeled with deuterium (26,26,26,27,27,27-hexadeuterated 1α,25-dihydroxyvitamin D3, or 1,25D-d6) is commonly used as internal standard for 1,25D liquid chromatography-mass spectrometry (LC-MS) quantification. In the present study using human breast cancer cell lines, the biological activity of 1,25D-d6 administered alone and in combination with two commonly used antineoplastic agents, 5-fluorouracil and etoposide, was evaluated. Using an MTT assay, flow cytometry, and western blots, our data demonstrated that 1,25D-d6 has effects similar to the natural hormone on cell proliferation, cell cycle, and apoptosis. Furthermore, the combination of 1,25D-d6 and etoposide enhances the antitumoral effects of both compounds. Interestingly, the antitumoral effect is higher in the more aggressive MDA-MB-231 breast cancer cell line. Our data indicate that 1,25D-d6 administered alone or in combination with chemotherapy could be a good experimental method for accurately quantifying active 1,25D levels in cultures or in biological fluids, on both in vitro breast cancer cell lines and in vivo animal experimental models. PMID:24378752

  18. Prognostic associations of 25 hydroxy vitamin D in NCIC CTG MA.21, a phase III adjuvant randomized clinical trial of three chemotherapy regimens in high-risk breast cancer.

    PubMed

    Lohmann, Ana Elisa; Chapman, Judy-Anne W; Burnell, Margot J; Levine, Mark Norman; Tsvetkova, Elena; Pritchard, Kathleen I; Gelmon, Karen A; O'Brien, Patti; Han, Lei; Rugo, Hope S; Albain, Kathy S; Perez, Edith A; Vandenberg, Theodore A; Chalchal, Haji I; Sawhney, Ravinder Pal Singh; Shepherd, Lois E; Goodwin, Pamela Jean

    2015-04-01

    Low vitamin D levels have been associated with poor breast cancer outcomes in observational studies. We examined the association of vitamin D blood levels with relapse-free survival (RFS), breast cancer-specific survival (BCSS), and overall survival (OS) in the MA.21 randomized clinical trial. Fasting blood was collected pre-chemotherapy in 934/2104 (44.4 %) of subjects; 25 hydroxy vitamin D was measured (radioimmunoassay, Diasorin) in one batch. Vitamin D was assessed as a transformed continuous factor, and categorically (quartiles and clinical classifications). Univariate and multivariate prognostic analyses (adjusted for treatment, stratification factors, and baseline imbalances) were performed using Cox models. Most patients were young (median 47.8 years), white (91.6 %) and premenopausal (69.4 %) with grade III (52 %), HER2 negative or missing (89.5 %), ER positive (61.9 %), T1-2 (89.4 %), N + (72.7 %) breast cancer. Compared to the full population, those with vitamin D levels were more likely to be white, PS 1 or 2, to have undergone mastectomy, and to have an ER + tumor. Mean vitamin D was 69.7 nmol/L (27.9 ng/ml) and did not vary by tumor subtype. The majority (80.5 %) had levels >50 nmol/L (20 ng/ml), considered adequate by Institute of Medicine. Continuous vitamin D was not multivariately associated with RFS, BCSS, or OS (p = 0.36, 0.26, 0.33, respectively); categorical vitamin D was also not associated with outcome. Vitamin D associations with RFS did not differ within ER/HER2 subgroups. There was no evidence that vitamin D blood level was associated with RFS, BCSS, and OS in MA.21; the majority of subjects had adequate vitamin D levels at study entry. PMID:25833209

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

    PubMed

    Piura, Benjamin

    2014-09-01

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

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

    PubMed

    Piura, Benjamin

    2014-09-01

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

  1. Mechanisms of Action of Adjuvants

    PubMed Central

    Awate, Sunita; Babiuk, Lorne A.; Mutwiri, George

    2013-01-01

    Adjuvants are used in many vaccines, but their mechanisms of action are not fully understood. Studies from the past decade on adjuvant mechanisms are slowly revealing the secrets of adjuvant activity. In this review, we have summarized the recent progress in our understanding of the mechanisms of action of adjuvants. Adjuvants may act by a combination of various mechanisms including formation of depot, induction of cytokines and chemokines, recruitment of immune cells, enhancement of antigen uptake and presentation, and promoting antigen transport to draining lymph nodes. It appears that adjuvants activate innate immune responses to create a local immuno-competent environment at the injection site. Depending on the type of innate responses activated, adjuvants can alter the quality and quantity of adaptive immune responses. Understanding the mechanisms of action of adjuvants will provide critical information on how innate immunity influences the development of adaptive immunity, help in rational design of vaccines against various diseases, and can inform on adjuvant safety. PMID:23720661

  2. Retinoblastoma: achieving new standards with methods of chemotherapy.

    PubMed

    Kaliki, Swathi; Shields, Carol L

    2015-02-01

    The management of retinoblastoma (RB) has dramatically changed over the past two decades from previous radiotherapy methods to current chemotherapy strategies. RB is a remarkably chemotherapy-sensitive tumor. Chemotherapy is currently used as a first-line approach for children with this malignancy and can be delivered by intravenous, intra-arterial, periocular, and intravitreal routes. The choice of route for chemotherapy administration depends upon the tumor laterality and tumor staging. Intravenous chemotherapy (IVC) is used most often in bilateral cases, orbital RB, and as an adjuvant treatment in high-risk RB. Intra-arterial chemotherapy (IAC) is used in cases with group C or D RB and selected cases of group E tumor. Periocular chemotherapy is used as an adjunct treatment in eyes with group D and E RB and those with persistent/recurrent vitreous seeds. Intravitreal chemotherapy is reserved for eyes with persistent/recurrent vitreous seeds. In this review, we describe the various forms of chemotherapy used in the management of RB. A database search was performed on PubMed, using the terms "RB," and "treatment," "chemotherapy," "systemic chemotherapy," "IVC," "IAC," "periocular chemotherapy," or "intravitreal chemotherapy." Relevant English language articles were extracted, reviewed, and referenced appropriately. PMID:25827539

  3. Adjuvant therapy for pancreas cancer in an era of value based cancer care

    PubMed Central

    Ahn, Daniel H.; Williams, Terence M.; Goldstein, Daniel A.; El-Rayes, Bassel; Bekaii-Saab, Tanios

    2016-01-01

    In resected pancreas cancer, adjuvant therapy improves outcomes and is considered the standard of care for patients who recover sufficiently post operatively. Chemotherapy or combined chemotherapy and radiation therapy (chemoradiation; CRT) are strategies used in the adjuvant setting. However, there is a lack of evidence to suggest whether the addition of RT to chemotherapy translates to an improvement in clinical outcomes. This is true even when accounting for the subset of patients with a higher risk for recurrence, such as those with R1 and lymph node positive disease. When considering the direct and indirect costs, impact on quality of life and questionable added clinical benefit, the true “net health benefit” from added RT to chemotherapy becomes more uncertain. Future directions, including the utilization of modern RT, integration of novel therapies, and intensifying chemotherapy regimens may improve outcomes in resected pancreas cancer. PMID:26620819

  4. Adjuvant therapy for pancreas cancer in an era of value based cancer care.

    PubMed

    Ahn, Daniel H; Williams, Terence M; Goldstein, Daniel A; El-Rayes, Bassel; Bekaii-Saab, Tanios

    2016-01-01

    In resected pancreas cancer, adjuvant therapy improves outcomes and is considered the standard of care for patients who recover sufficiently post operatively. Chemotherapy or combined chemotherapy and radiation therapy (chemoradiation; CRT) are strategies used in the adjuvant setting. However, there is a lack of evidence to suggest whether the addition of RT to chemotherapy translates to an improvement in clinical outcomes. This is true even when accounting for the subset of patients with a higher risk for recurrence, such as those with R1 and lymph node positive disease. When considering the direct and indirect costs, impact on quality of life and questionable added clinical benefit, the true "net health benefit" from added RT to chemotherapy becomes more uncertain. Future directions, including the utilization of modern RT, integration of novel therapies, and intensifying chemotherapy regimens may improve outcomes in resected pancreas cancer. PMID:26620819

  5. Utility of adjuvant systemic therapy in melanoma

    PubMed Central

    Eggermont, A. M. M.; Testori, A.; Marsden, J.; Hersey, P.; Quirt, I.; Petrella, T.; Gogas, H.; MacKie, R. M.; Hauschild, A.

    2009-01-01

    The lack of effective drugs in stage IV melanoma has impacted the effectiveness of adjuvant therapies in stage II/III disease. To date, chemotherapy, immunostimulants and vaccines have been used with minimal success. Interferon (IFN) has shown an effect on relapse-free survival (RFS) in several clinical trials; however, without a clinically significant effect on overall survival (OS). A recently conducted meta-analysis demonstrated prolongation of disease-free survival (DFS) in 7% and OS benefit in 3% of IFN-treated patients when compared with observation-only patients. There were no clear differences for the dose and duration of treatment observed. Observation is still an appropriate control arm in adjuvant clinical trials. Regional differences exist in Europe in the adjuvant use of IFN. In Northwest Europe, IFN is infrequently prescribed. In Central and Mediterranean Europe, dermatologists commonly prescribe low-dose IFN therapy for AJCC stage II and III disease. High-dose IFN regimens are not commonly used. The population of patients that may benefit from IFN needs to be further characterised, potentially by finding biomarkers that can predict response. Such studies are ongoing. PMID:19617295

  6. Novel adjuvant systems.

    PubMed

    McCluskie, M J; Weeratna, R D

    2001-11-01

    Vaccination remains the single most valuable tool in the prevention of infectious disease. Nevertheless, there exists a need to improve the performance of existing vaccines such that fewer boosts are needed or to develop novel vaccines. For the development of effective vaccines for humans, a great need exists for safe and effective adjuvants. A number of novel adjuvants have been reported in recent years including: i) bacterial toxins such as cholera toxin, CT, and the Escherichia coli heat-labile enterotoxin, LT; ii) less toxic derivatives of CT and LT; iii) endogenous human immunomodulators, such as IL-2, IL-12, GM-CSF; iv) hormones; v) lipopeptides; vi) saponins, such as QS-21; vii) synthetic oligonucleotides containing CpG motifs (CpG ODN); viii) lipid 'A derivatives, such as monophosphoryl lipid A, MPL, and ix) muramyl dipeptide (MDP) derivatives. Herein, we will review recent findings using these novel adjuvant systems. PMID:12455400

  7. [Induction chemotherapy for locally advanced cervical cancer].

    PubMed

    Morkhov, K Yu; Nechushkina, V M; Kuznetsov, V V

    2015-01-01

    The main methods of treatment for cervical cancer are surgery, radiotherapy or their combination. During past two decades chemotherapy are increasingly being used not only in patients with disseminated forms of this disease but also in patients undergoing chemoradiotherapy or as induction therapy. Possibilities of adjuvant chemotherapy for cervical cancer are being studied. According to A.D.Kaprin and V.V. Starinskiy in 2013 in Russia, 32% of patients with newly diagnosed cervical cancer underwent only radiation therapy, 32%--combined or complex treatment, 27.3%--only surgery, and just 8.7%--chemoradiotherapy. PMID:26087600

  8. Understanding Chemotherapy

    MedlinePlus

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

  9. Predicting response to chemotherapy with early-stage lung cancer.

    PubMed

    Rosell, Rafael; Taron, Miquel; Massuti, Bartomeu; Mederos, Nuria; Magri, Ignacio; Santarpia, Mariacarmela; Sanchez, Jose Miguel

    2011-01-01

    A recent meta-analysis of 11,107 patients with non-small cell lung cancer who had undergone surgical resection showed that the 5-year survival benefit of adjuvant chemotherapy was 4%, and that of adjuvant chemoradiotherapy was 5%. Two trials have shown a trend toward improved survival with adjuvant paclitaxel plus carboplatin. However, the benefit of adjuvant treatment remains suboptimal. We must distinguish between patients who will not relapse-and who can thus be spared adjuvant treatment-and those who will-for whom adjuvant treatment must be personalized. Several gene expression signatures, generally containing nonoverlapping genes, provide similar predictive information on clinical outcome, and a model combining several signatures did not perform better than did each of the signatures separately. The invasiveness gene signature, containing 186 genes, includes genes involved in the nuclear factor κB pathway, the RAS-mitogen-activated protein kinase pathway, and epigenetic control of gene expression. A 15-gene signature has identified JBR.10 patients who are more sensitive to adjuvant chemotherapy. PMID:21263267

  10. Adjuvant systemic treatment for individual patients with triple negative breast cancer.

    PubMed

    Oakman, Catherine; Moretti, Erica; Galardi, Francesca; Biagioni, Chiara; Santarpia, Libero; Biganzoli, Laura; Di Leo, Angelo

    2011-10-01

    Chemotherapy is the only evidence based adjuvant systemic treatment option in triple negative breast cancer (TNBC). Despite emerging results for targeted biological therapies for this subpopulation, lack of robust results does not currently support their use beyond the confines of a clinical trial. Conventional systemic chemotherapy remains the standard of care and is curative in a minority of patients. There is no defined standard chemotherapy and there is currently no robust, prospective, randomized data to advise different use of specific chemotherapy agents in TNBC as compared to non-TNBC. Data suggest high sensitivity to chemotherapy, however it is yet to be determined whether this increased sensitivity is agent/regimen specific or whether it reflects general chemosensitivity. This review will focus on systemic chemotherapy in early TNBC, particularly anthracyclines and platinums, and potential predictive tools to guide chemotherapy use. PMID:22015281

  11. A Comparison of Proposed Biosimilar LA-EP2006 and Reference Pegfilgrastim for the Prevention of Neutropenia in Patients With Early-Stage Breast Cancer Receiving Myelosuppressive Adjuvant or Neoadjuvant Chemotherapy: Pegfilgrastim Randomized Oncology (Supportive Care) Trial to Evaluate Comparative Treatment (PROTECT-2), a Phase III, Randomized, Double-Blind Trial

    PubMed Central

    Donskih, Roman; Jones, C. Michael; Nixon, Allen; Vidal, Maria J.; Nakov, Roumen; Singh, Pritibha; Schaffar, Gregor; Gascón, Pere; Harbeck, Nadia

    2016-01-01

    Background. Pegfilgrastim is widely used for the prevention of chemotherapy-induced neutropenia. In highly regulated markets, there are currently no approved biosimilars of pegfilgrastim. Pegfilgrastim Randomized Oncology (Supportive Care) Trial to Evaluate Comparative Treatment (PROTECT-2) was a confirmatory efficacy and safety study designed to compare proposed biosimilar LA-EP2006 with reference pegfilgrastim (Neulasta, Amgen) in early-stage breast cancer patients receiving adjuvant or neoadjuvant myelosuppressive chemotherapy. Methods. A total of 308 patients were randomized to LA-EP2006 or reference pegfilgrastim. Each patient received TAC (intravenous docetaxel 75 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2) on day 1 of each cycle, for six or more cycles. Pegfilgrastim (LA-EP2006 or reference) was given subcutaneously (6 mg in 0.6 mL) on day 2 of each cycle. The primary endpoint was duration of severe neutropenia (DSN) during cycle 1 (number of consecutive days with an absolute neutrophil count <0.5 × 109/L), with equivalence confirmed if 90% and 95% confidence intervals (CIs) were within a 1-day margin. Results. Baseline characteristics were well balanced. DSN was equivalent between groups at mean ± SD 1.36 ± 1.13 (LA-EP2006, n = 155) and 1.19 ± 0.98 (reference, n = 153) in cycle 1. With a treatment difference (reference minus LA-EP2006) of −0.16 days (90% CI −0.36 to 0.04; 95% CI −0.40 to 0.08), LA-EP2006 was equivalent to reference pegfilgrastim. Secondary efficacy parameters were similar between groups during cycle 1 and across cycles. Safety profiles were also similar between groups. No neutralizing antibodies against pegfilgrastim, filgrastim, or polyethylene glycol were detected. Conclusion. LA-EP2006 and reference pegfilgrastim were therapeutically equivalent and comparable regarding efficacy and safety in the prevention of neutropenia in patients with early-stage breast cancer receiving TAC. Implications for Practice: The

  12. [New options in adjuvant endocrine therapy in breast cancer].

    PubMed

    Saltel-Fulero, Aurélien; Donnadieu, Anne; Leman-Detours, Solenne; Cottu, Paul

    2016-01-01

    Endocrine therapy is a compulsory step in the adjuvant management of early breast cancer expressing the estrogen receptor, by reducing as much as possible serum and tissue levels of estrogens. Tamoxifen is the standard therapy for non-menopausal women. Ovarian function suppression, in addition to exemestane or tamoxifen, could be an alternative option for young women at high risk of recurrence and non menopausal after adjuvant or neo-adjuvant chemotherapy. Recent studies show a trend for improvement of overall survival and disease-free-survival with aromatase inhibitors among postmenopausal women. However, safety of aromatase inhibitors is controversial and adverse events may lead to switch for tamoxifen with no loss of efficacy. Extension therapy by tamoxifen or aromatase inhibitor after five years of tamoxifen and for a total duration of ten years significantly improves overall survival. There is to date no data supporting the extension therapy after five years of aromatase inhibitor. PMID:26675809

  13. Adjuvant Therapy for Melanoma

    PubMed Central

    Davar, Diwakar; Tarhini, Ahmad A.

    2012-01-01

    Estimates from the U.S. Surveillance, Epidemiology, and End Results (SEER) registry suggest that melanoma incidence will reach 70,230 in 2011, of which 8,790 will die. The rising incidence and predilection for young individuals makes this tumor a leading source of lost productive years in the society. High-dose interferon-α2b is the only agent approved for adjuvant therapy of melanoma; the improvement in relapse-free survival has been observed across nearly all published studies and meta-analyses. However toxicity affects compliance and current research is focusing upon biomarkers that may allow selection of patients with greater likelihood of response, and exploring new agents either singly or in combination that may improve upon the benefit of IFN. In this article, we review the data for the adjuvant therapy of malignant melanoma - focusing on the results obtained with various regimens testing the several formulations of interferon-α2, and the adjuvant studies of vaccines and radiotherapy. Recent advances in the treatment of metastatic disease have established a role for CTLA-4 blockade and BRAF-inhibition, and raising hopes that these agents may have a role in the adjuvant setting. At present, several trials investigating combinations of novel agents with existing immunomodulators are underway. PMID:22453021

  14. Laser vaccine adjuvants

    PubMed Central

    Kashiwagi, Satoshi; Brauns, Timothy; Gelfand, Jeffrey; Poznansky, Mark C

    2014-01-01

    Immunologic adjuvants are essential for current vaccines to maximize their efficacy. Unfortunately, few have been found to be sufficiently effective and safe for regulatory authorities to permit their use in vaccines for humans and none have been approved for use with intradermal vaccines. The development of new adjuvants with the potential to be both efficacious and safe constitutes a significant need in modern vaccine practice. The use of non-damaging laser light represents a markedly different approach to enhancing immune responses to a vaccine antigen, particularly with intradermal vaccination. This approach, which was initially explored in Russia and further developed in the US, appears to significantly improve responses to both prophylactic and therapeutic vaccines administered to the laser-exposed tissue, particularly the skin. Although different types of lasers have been used for this purpose and the precise molecular mechanism(s) of action remain unknown, several approaches appear to modulate dendritic cell trafficking and/or activation at the irradiation site via the release of specific signaling molecules from epithelial cells. The most recent study, performed by the authors of this review, utilized a continuous wave near-infrared laser that may open the path for the development of a safe, effective, low-cost, simple-to-use laser vaccine adjuvant that could be used in lieu of conventional adjuvants, particularly with intradermal vaccines. In this review, we summarize the initial Russian studies that have given rise to this approach and comment upon recent advances in the use of non-tissue damaging lasers as novel physical adjuvants for vaccines. PMID:25424797

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

    PubMed Central

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

    2012-01-01

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

  16. What make differences in the outcome of adjuvant treatments for resected gastric cancer?

    PubMed Central

    Nakajima, Toshifusa; Fujii, Masashi

    2014-01-01

    After a long history of Dark Age of adjuvant chemotherapy for gastric cancer, definite evidences of survival benefit from adjuvant treatment have been reported since 2000s. These survival benefits are likely attributed to something new approach different from pervious studies. In 2001, South West Oncology Group INT0116 trial yielded survival benefit in curatively resected gastric cancer patients with postoperative chemoradiotherapy [5-fluorouracil (5-FU) + Leucovorin + radiotherapy], followed by positive result by MAGIC Trial, employing peri-operative(pre- and postoperative chemotherapy with Epirubicin, cisplatin (CDDP), 5-fluorouracil (ECF) regimen in patients with curative resection. A novel drug [S1: ACTS-GC (Adjuvant chemotherapy trial of TS-1 for gastric cancer) in 2007], or new drug combination chemotherapys [CDDP + 5-FU: FNCLCC/FFCD (Federation Nationale des Centres de Lutte contre le cancer/Federation Francophone de Cancerologie Digestive) in 2011, Capecitabine + Oxaliplatin: CLASSIC in 2012] also produced positive results in terms of improved prognosis. Neoadjuvant or perioperative chemotherapy, novel anti-cancer drugs, and chemoradiotherapy might be the key words to develop further improvement in the adjuvant treatment of resectable gastric cancer. Moreover, it is not new but still true to stress the importance of D2 surgery as the baseline treatment in order to minimize the amount of residual tumor after surgery. PMID:25206264

  17. Adjuvant Immunotherapy of Melanoma, and Development of New Approaches Using the Neo- Adjuvant Approach in Melanoma

    PubMed Central

    Davar, Diwakar; Tarhini, Ahmad

    2013-01-01

    Melanoma is the third most common skin cancer but the leading cause of death from cutaneous malignancies. While early-stage disease is frequently cured by surgical resection with excellent long-term survival, patients with deeper primary lesions (AJCC stage IIB-C) and those with microscopic (IIIA) or clinically evident regional lymph node or in-transit metastases (IIIB-C) have an increased risk of relapse and death–the latter approaching 70% or more at 5 years. In patients at high-risk of recurrence/metastases, adjuvant therapy with high-dose interferon alpha-2b (HDI) following definitive surgical resection has been shown to improve relapse free and overall survival. Neo-adjuvant chemotherapy and/or radiotherapy have offered the prospect to improve regional recurrence risk and overall survival in several solid tumors. The advent of effective new molecularly targeted therapies for metastatic disease and new immunotherapies that overcome checkpoints of immune response have augmented the range of new options that are in current trial evaluation to determine their role as potential adjuvant therapies, alone and in combination with one another, and the established modality of IFNα. The differential characteristics of the host immune response between early and advanced melanoma provide a strong mechanistic rationale for the use of neo-adjuvant immunotherapeutic approaches in melanoma, and the opportunity to evaluate the mechanism of action suggest neoadjuvant trial evaluation for each of the new candidate agents and combinations of interest. Several neo-adjuvant trials have been conducted in the phase II setting, which have illuminated the mechanism of IFNα, as well as providing insight to the effects of anti-CTLA4 blocking antibodies. These agents (anti-CTLA4 blocking antibody ipilimumab [BMS], and BRAF inhibitor vemurafenib [Genentech]) are likely to be followed by other immunotherapies that may overcome the PD-1 checkpoint (anti-PD1 [BMS, Merck, Curetech] and anti

  18. Predictive role of HER2/neu, topoisomerase-II-alpha, and tissue inhibitor of metalloproteinases (TIMP-1) for response to adjuvant taxane-based chemotherapy in patients with intermediate-risk breast cancer: results from the WSG-AGO EC-Doc trial.

    PubMed

    Erber, Ramona; Gluz, Oleg; Brünner, Nils; Kreipe, Hans Heinrich; Pelz, Enrico; Kates, Ronald; Bartels, Annette; Huober, Jens; Mohrmann, Svjetlana; Moustafa, Zehra; Liedtke, Cornelia; Möbus, Volker; Augustin, Doris; Thomssen, Christoph; Jänicke, Fritz; Kiechle, Marion; Kuhn, Walther; Nitz, Ulrike; Harbeck, Nadia; Hartmann, Arndt

    2015-04-01

    Taxane-anthracycline-based adjuvant chemotherapy is standard of care in patients with node-positive breast cancer (BC) but is also associated with severe side effects and significant costs. It is yet unclear, which biomarkers would predict benefit from taxanes and/or general chemoresistance. In this study, we investigate a large cohort of patients with intermediate-risk BC treated within the WSG EC-DOC Trial for the predictive impact of topoisomerase-II-alpha, HER2/neu, and TIMP-1. Tumor tissue was available in a representative cohort of 772 cases of the WSG EC-DOC Trial collective which compared 4xEC-4xDoc versus 6xCEF/CMF. In addition to hormone receptor status and Ki-67, HER2/neu+ and topoisomerase-II-alpha status using fluorescence in situ hybridisation (FISH) and immunohistochemistry, TIMP-1 using immunohistochemistry, and aneuploidy of chromosome 17 using FISH were evaluated and correlated with outcome and taxane benefit. There was significant superiority of EC-Doc over CEF regarding 5-year DFS (90 vs. 80 %, respectively, p = 0.006) particularly in patient subgroups defined by HR+, HER2/neu+, high proliferation (i.e., Ki-67 ≥ 20 %), patient age >50 years old and normal chromosome 17 status, high TIMP-1 and low topoisomerase-II-alpha protein expression. Significant prognostic factors in multivariate analysis were EC-Doc therapy (HR = 0.61; 95 %CI 0.38-0.986), age <50 years old (HR = 1.682; 95 %CI 1.025-2.579), centrally assessed grade 3 (HR = 4.657; 95 %CI 1.809-11.989), and high Ki-67 (HR = 2.232; 95 %CI 1.209-4.121). Interestingly, we observed a significant interaction between treatment arm (EC-Doc vs. CEF) and high topoisomerase-II-alpha protein expression (HR = 0.427; 95 %CI 0.203-0.900) in multivariate interaction analysis. Despite of univariate predictive effect of HER2/neu status among other factors only topoisomerase-II-alpha protein expression was associated with significant benefit from EC-Doc compared to CEF by multivariate interaction analysis

  19. Capecitabine Induced Multifocal Leukoencephalopathy: Do We Have Always to Switch off the Chemotherapy?

    PubMed

    Bougea, Anastasia; Voskou, Panagiota; Kilidireas, Constantinos; Andreadou, Elisabeth

    2016-01-01

    Capecitabine is a well tolerated and safe 5-fluorouracil agent for adjuvant, neoadjuvant chemotherapy or metastatic cases. Neurological side effects require discontinuation of chemotherapy. We report this unique case of a 50-year-old female, who presented an isolated episode of dysarthria and ataxia under bevacizumab, capecitabine, and oxaliplatin treatment due to reversible multifocal leukoencephalopathy that did not recur after readministration of chemotherapy. PMID:26966603

  20. Impact of Adjuvant Radiotherapy on Survival after Pancreatic Cancer Resection: An Appraisal of Data from the National Cancer Data Base

    PubMed Central

    Kooby, David A.; Gillespie, Theresa W.; Liu, Yuan; Byrd-Sellers, Johnita; Landry, Jerome; Bian, John; Lipscomb, Joseph

    2016-01-01

    Purpose The impact of adjuvant radiotherapy for pancreatic adenocarcinoma (PAC) remains controversial. We examined effects of adjuvant therapy on overall survival (OS) in PAC, using the National Cancer Data Base (NCDB). Methods Patients with resected PAC from 1998 to 2002 were queried from the NCDB. Factors associated with receipt of adjuvant chemotherapy (ChemoOnly) versus adjuvant chemoradiotherapy (ChemoRad) versus no adjuvant treatment (NoAdjuvant) were assessed. Cox proportional hazard modeling was used to examine effect of adjuvant therapy type on OS. Propensity scores (PS) were developed for each treatment arm and used to produce matched samples for analysis to minimize selection bias. Results From 1998 to 2002, a total of 11,526 patients underwent resection of PAC. Of these, 1,029 (8.9 %) received ChemoOnly, 5,292 (45.9 %) received ChemoRad, and 5,205 (45.2 %) received NoAdjuvant. On univariate analysis, factors associated with improved OS included: younger age, higher income, higher facility volume, lower tumor stage and grade, negative margins and nodes, and absence of adjuvant therapy. On multivariate analysis with matched PS, factors independently associated with improved OS included: younger age, higher income, higher facility volume, later year of diagnosis, smaller tumor size, lower tumor stage, and negative tumor margins and nodes. ChemoRad had the best OS (hazard ratio 0.70, 95 % confidence interval 0.61–0.80) in a PS matched comparison with ChemoOnly (hazard ratio 1.04, 95 % confidence interval 0.93–1.18) and NoAdjuvant (index). Conclusions Adjuvant chemotherapy with radiotherapy is associated with improved OS after PAC resection in a large population from the NCDB. On the basis of these analyses, radiotherapy should be a part of adjuvant therapy for PAC. PMID:23771249

  1. Chemotherapy for Thyroid Cancer

    MedlinePlus

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

  2. Types of chemotherapy

    MedlinePlus

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

  3. Adjuvant Therapy Trials.

    PubMed

    Ursem, Carling; Van Loon, Katherine; Venook, Alan

    2016-01-01

    In 2015, ramucirumab and TAS-102 became the 10th and 11th drugs approved by the Food and Drug administration for the treatment of patients with colorectal cancer, not counting leucovorin, and yet only 3 agents, 5-fluorouracil, capecitabine, and oxaliplatin, have proven benefit in adjuvant treatment. In fact, there have been no additions (and 1 subtraction levamisole) to our arsenal of therapies for patients with stages II and III colon cancer for more than a decade. How did we get here? Are we stuck? And how do we move forward? PMID:27341598

  4. The impact of combined radiation and chemotherapy on outcome in uterine papillary serous carcinoma compared to chemotherapy alone

    PubMed Central

    Nutter, Benjamin; Abdul-Karim, Fadi; Amarnath, Sudha; Rose, Peter G

    2016-01-01

    Objective To investigate the impact of pelvic radiation on survival in patients with uterine serous carcinoma (USC) who received adjuvant chemotherapy. Methods Patients with stage I-IV USC were identified from the Surveillance, Epidemiology, and End Results program 2000 to 2009. Patients were included if treated with surgery and chemotherapy. Patients were divided into two groups: those who received chemotherapy and pelvic radiation therapy (CT_RT) and those who received chemotherapy only (CT). Kaplan-Meier curves and Cox regression proportional hazard models were used. Results Of the 1,838 included patients, 1,272 (69%) were CT and 566 (31%) were CT_RT. Adjuvant radiation was associated with significant improvement in overall survival (OS; p<0.001) and disease-specific survival (DSS; p<0.001) for entire cohort. These findings were consistent for the impact of radiation on OS (p<0.001) and DSS (p<0.001) in advanced stage (III-IV) disease but not for early stage (I–II) disease (p=0.21 for OS and p=0.82 for DSS). In multivariable analysis adjusting for age, stage, race and extent of lymphadenectomy, adjuvant radiation was a significant predictor of OS and DSS for entire cohort (p=0.003 and p=0.05) and in subset of patients with stage III (p=0.02 and p=0.07) but not for patients with stage I (p=0.59 and p=0.49), II (p=0.83 and p=0.82), and IV USC (p=0.50 and p=0.96). Other predictors were stage, positive cytology, African American race and extent of lymphadenectomy. Conclusion In USC patients who received adjuvant chemotherapy, adjuvant radiation was associated with significantly improved outcome in stage III disease but not for other stages. Positive cytology, extent of lymphadenectomy and African race were significant predictors of outcome. PMID:26463437

  5. Acute hyperammonemic encephalopathy after 5-fluorouracil based chemotherapy

    PubMed Central

    Yi, Hee Jung; Hong, Kyung Sook; Moon, Nara; Chung, Soon Sup; Lee, Ryung-Ah

    2016-01-01

    5-Fluorouracil (5-FU) based chemotherapy has been commonly used to treat metastatic or advanced colon cancer as an adjuvant chemotherapy. Although the side effects of 5-FU such as gastrointestinal problems and neutropenia and thrombocytopenia are common, not many cases of 5-FU related encephalopathy are reported. Hyperammonemic encephalopathy is a rare central nervous system toxicity following 5-FU chemotherapy manifesting as altered mental status with elevated ammonia levels with no radiologic abnormality. We report one case of 5-FU induced hyperammonemic encephalopathy occurring after Folfox4 (oxaliplatin, folinic acid and 5-fluorouracil) chemotherapy in a colon cancer patient who presented with confused mental status soon after the chemotherapy and review the 5-FU related encephalopathy. PMID:26942162

  6. Acute hyperammonemic encephalopathy after 5-fluorouracil based chemotherapy.

    PubMed

    Yi, Hee Jung; Hong, Kyung Sook; Moon, Nara; Chung, Soon Sup; Lee, Ryung-Ah; Kim, Kwang Ho

    2016-03-01

    5-Fluorouracil (5-FU) based chemotherapy has been commonly used to treat metastatic or advanced colon cancer as an adjuvant chemotherapy. Although the side effects of 5-FU such as gastrointestinal problems and neutropenia and thrombocytopenia are common, not many cases of 5-FU related encephalopathy are reported. Hyperammonemic encephalopathy is a rare central nervous system toxicity following 5-FU chemotherapy manifesting as altered mental status with elevated ammonia levels with no radiologic abnormality. We report one case of 5-FU induced hyperammonemic encephalopathy occurring after Folfox4 (oxaliplatin, folinic acid and 5-fluorouracil) chemotherapy in a colon cancer patient who presented with confused mental status soon after the chemotherapy and review the 5-FU related encephalopathy. PMID:26942162

  7. Carbohydrate-based immune adjuvants

    PubMed Central

    Petrovsky, Nikolai; Cooper, Peter D

    2011-01-01

    The role for adjuvants in human vaccines has been a matter of vigorous scientific debate, with the field hindered by the fact that for over 80 years, aluminum salts were the only adjuvants approved for human use. To this day, alum-based adjuvants, alone or combined with additional immune activators, remain the only adjuvants approved for use in the USA. This situation has not been helped by the fact that the mechanism of action of most adjuvants has been poorly understood. A relative lack of resources and funding for adjuvant development has only helped to maintain alum’s relative monopoly. To seriously challenge alum’s supremacy a new adjuvant has many major hurdles to overcome, not least being alum’s simplicity, tolerability, safety record and minimal cost. Carbohydrate structures play critical roles in immune system function and carbohydrates also have the virtue of a strong safety and tolerability record. A number of carbohydrate compounds from plant, bacterial, yeast and synthetic sources have emerged as promising vaccine adjuvant candidates. Carbohydrates are readily biodegradable and therefore unlikely to cause problems of long-term tissue deposits seen with alum adjuvants. Above all, the Holy Grail of human adjuvant development is to identify a compound that combines potent vaccine enhancement with maximum tolerability and safety. This has proved to be a tough challenge for many adjuvant contenders. Nevertheless, carbohydrate-based compounds have many favorable properties that could place them in a unique position to challenge alum’s monopoly over human vaccine usage. PMID:21506649

  8. Adjuvant therapy for gastric cancer: What have we learned since INT0116?

    PubMed Central

    Jácome, Alexandre A; Sankarankutty, Ajith K; dos Santos, José Sebastião

    2015-01-01

    Gastric cancer is one of the main cancer-related causes of death worldwide. The curative treatment of gastric cancer consists of tumor resection and lymphadenectomy. However, surgical treatment alone is associated with high recurrence rates. Adjuvant treatment strategies have been studied over the last decades, but there have been controversial results from the initial studies. The pivotal INT0116 study demonstrated that the use of adjuvant chemoradiotherapy with 5-fluorouracil increases relapse-free and overall survival, and it has been adopted across the Western world. The high toxicity of radiochemotherapy and suboptimal surgical treatment employed, with fewer than 10% of the patients submitted to D2 lymphadenectomy, were the main study limitations. Since its publication, other adjuvant treatment modalities have been studied, and radiochemotherapy is being refined to improve its efficacy and safety. A multimodal approach has been demonstrated to significantly increase relapse-free and overall survival, and it can be offered in the form of perioperative chemotherapy, adjuvant chemoradiotherapy or adjuvant chemotherapy, regardless of the extent of lymphadenectomy. The objective of the present review is to report the major advances obtained in the last decades in the adjuvant treatment of gastric cancer as well as the perspectives of treatment based on recent knowledge of the molecular biology of the disease. PMID:25852269

  9. Adjuvant Therapy: Melanoma

    PubMed Central

    Davar, Diwakar; Tarhini, Ahmad; Kirkwood, John M.

    2011-01-01

    With an incidence that is increasing at 2–5% per year, cutaneous melanoma is an international scourge that disproportionately targets young individuals. Despite much research, the treatment of advanced disease is still quite challenging. Immunotherapy with high-dose interferon-α2b or interleukin-2 benefits a select group of patients in the adjuvant and metastatic settings, respectively, with significant attendant toxicity. Advances in the biology of malignant melanoma and the role of immunomodulatory therapy have produced advances that have stunned the field. In this paper, we review the data for the use of interferon-α2b in various dosing ranges, vaccine therapy, and the role of radiotherapy in the adjuvant setting for malignant melanoma. Recent trials in the metastatic setting using anticytoxic T-lymphocyte antigen-4 (anti-CTLA-4) monoclonal antibody therapy and BRAF inhibitor therapy have demonstrated clear benefit with prolongation of survival. Trials investigating combinations of these novel agents with existing immunomodulators are at present underway. PMID:22220281

  10. Association Between Geographic Access to Cancer Care, Insurance, and Receipt of Chemotherapy: Geographic Distribution of Oncologists and Travel Distance

    PubMed Central

    Lin, Chun Chieh; Bruinooge, Suanna S.; Kirkwood, M. Kelsey; Olsen, Christine; Jemal, Ahmedin; Bajorin, Dean; Giordano, Sharon H.; Goldstein, Michael; Guadagnolo, B. Ashleigh; Kosty, Michael; Hopkins, Shane; Yu, James B.; Arnone, Anna; Hanley, Amy; Stevens, Stephanie; Hershman, Dawn L.

    2015-01-01

    Purpose Geographic access to care may be associated with receipt of chemotherapy but has not been fully examined. This study sought to evaluate the association between density of oncologists and travel distance and receipt of adjuvant chemotherapy for colon cancer within 90 days of colectomy. Patients and Methods Patients in the National Cancer Data Base with stage III colon cancer, diagnosed between 2007 and 2010, and age 18 to 80 years were selected. Generalized estimating equation clustering by hospital service area was conducted to examine the association between geographic access and receipt of oncology services, controlling for patient sociodemographic and clinical characteristics. Results Of 34,694 patients in the study cohort, 75.7% received adjuvant chemotherapy within 90 days of colectomy. Compared with travel distance less than 12.5 miles, patients who traveled 50 to 249 miles (odds ratio [OR], 0.87; P = .009) or ≥ 250 miles (OR, 0.36; P < .001) had decreased likelihood of receiving adjuvant chemotherapy. Density level of oncologists was not statistically associated with receipt of adjuvant chemotherapy (low v high density: OR, 0.98; P = .77). When stratifying analyses by insurance status, non–privately insured patients who resided in areas with low density of oncologists were less likely to receive adjuvant chemotherapy (OR, 0.85; P = .03). Conclusion Increased travel burden was associated with a decreased likelihood of receiving adjuvant chemotherapy, regardless of insurance status. Patients with nonprivate insurance who resided in low-density oncologist areas were less likely to receive adjuvant chemotherapy. If these findings are validated prospectively, interventions to decrease geographic barriers may improve the timeliness and quality of colon cancer treatment. PMID:26304878

  11. Have adjuvant tyrosine kinase inhibitors lost their shine?

    PubMed Central

    Sabari, Joshua K.

    2016-01-01

    Despite broad advances in molecularly targeted therapies, lung cancer remains the leading cause of cancer related mortality in the United States. Epidermal growth factor receptor (EGFR) mutations occur in approximately 17% of advanced non-small cell lung cancer (NSCLC) in the US population. The remarkable efficacy of small-molecule EGFR tyrosine kinase inhibitors (TKIs) in this unique subset of patients has revolutionized the therapeutic approach to lung cancer. The success of these agents in the metastatic setting leads to the logical question of what role these drugs may have in the adjuvant setting for patients with earlier stage disease. RADIANT, an international randomized, double-blind, placebo controlled phase III study in patients with completely resected stage IB to IIIA NSLC whose tumors expressed EGFR by IHC and EGFR amplification by FISH, attempted to answer the question of whether erlotinib would improve disease free survival and overall survival in the adjuvant setting. While RADIANT does not conclude for or against adjuvant use of EGFR-TKIs, all data points towards benefit in a selected population. As clinicians, we must continue to enroll to potentially practice changing therapeutic neoadjuvant and adjuvant chemotherapy studies internationally. PMID:27568486

  12. Have adjuvant tyrosine kinase inhibitors lost their shine?

    PubMed

    Sabari, Joshua K; Chaft, Jamie E

    2016-08-01

    Despite broad advances in molecularly targeted therapies, lung cancer remains the leading cause of cancer related mortality in the United States. Epidermal growth factor receptor (EGFR) mutations occur in approximately 17% of advanced non-small cell lung cancer (NSCLC) in the US population. The remarkable efficacy of small-molecule EGFR tyrosine kinase inhibitors (TKIs) in this unique subset of patients has revolutionized the therapeutic approach to lung cancer. The success of these agents in the metastatic setting leads to the logical question of what role these drugs may have in the adjuvant setting for patients with earlier stage disease. RADIANT, an international randomized, double-blind, placebo controlled phase III study in patients with completely resected stage IB to IIIA NSLC whose tumors expressed EGFR by IHC and EGFR amplification by FISH, attempted to answer the question of whether erlotinib would improve disease free survival and overall survival in the adjuvant setting. While RADIANT does not conclude for or against adjuvant use of EGFR-TKIs, all data points towards benefit in a selected population. As clinicians, we must continue to enroll to potentially practice changing therapeutic neoadjuvant and adjuvant chemotherapy studies internationally. PMID:27568486

  13. The adjuvanted influenza vaccines with novel adjuvants: experience with the MF59-adjuvanted vaccine.

    PubMed

    Podda, A

    2001-03-21

    Elderly people and subjects with underlying chronic diseases are at increased risk for influenza and related complications. Conventional influenza vaccines provide only limited protection in the elderly population. In order to enhance the immune response to influenza vaccines, several adjuvants have been evaluated. Among these, an oil in water adjuvant emulsion containing squalene, MF59, has been combined with subunit influenza antigens and tested in clinical trials in comparison with non-adjuvanted conventional vaccines. Data from a clinical database of over 10000 elderly subjects immunised with this adjuvanted vaccine (Fluad, Chiron Vaccines, Siena, Italy) demonstrate that, although common postimmunisation reactions are more frequent in recipients of the adjuvanted vaccine, this vaccine is well tolerated, also after re-immunisation in subsequent influenza seasons. Immunogenicity analyses demonstrate a consistently higher immune response with statistically significant increases of postimmunisation geometric mean titres, and of seroconversion and seroprotection rates compared to non-adjuvanted subunit and split influenza vaccines, particularly for the A/H3N2 and the B strains. The higher immunogenicity profile of the MF59-adjuvanted vaccine is maintained also after subsequent immunisations. An even higher adjuvant effect was shown in subjects with low pre-immunisation titre and in those affected by chronic underlying diseases. In conclusion, the addition of MF59 to subunit influenza vaccines enhances significantly the immune response in elderly subjects without causing clinically important changes in the safety profile of the influenza vaccine. PMID:11257408

  14. Adjuvants and delivery systems for antifungal vaccines: current state and future developments.

    PubMed

    Portuondo, Deivys Leandro F; Ferreira, Lucas S; Urbaczek, Ana C; Batista-Duharte, Alexander; Carlos, Iracilda Z

    2015-01-01

    Mycoses are gaining increasing attention in modern medicine because of the increase in diseases associated with opportunistic fungal infections. Despite the recognized role of the immune system in the control of fungal infections, no antifungal vaccines are currently licensed for use in humans. However, numerous vaccine candidates are being developed in many laboratories, as proof of the renewed interest in integrating or replacing chemotherapy with vaccines to reduce antibiotic use and consequently limit drug resistance and toxicity. In the effort to use safer and simpler fungal antigens for vaccinations, adjuvants have become relevant as immunostimulators to elicit successful protective immune responses. To address the relevant role of adjuvants as determinants in the balance of vaccine efficacy and safety, an updated and critical review of the adjuvants used in preclinical antifungal vaccines is presented, and prospective trends are addressed. Selected recent papers and other historically relevant and innovative strategies using adjuvants in experimental fungal vaccines are highlighted. PMID:25362733

  15. Efficacy and safety analysis of chemotherapy for advanced colitis-associated colorectal cancer in Japan.

    PubMed

    Nio, Kenta; Higashi, Daijiro; Kumagai, Hozumi; Arita, Shuji; Shirakawa, Tsuyoshi; Nakashima, Koji; Shibata, Yoshihiro; Esaki, Motohiro; Manabe, Tatsuya; Nagai, Shuntaro; Ueki, Takashi; Nakano, Michitaka; Ariyama, Hiroshi; Kusaba, Hitoshi; Hirahashi, Minako; Oda, Yoshinao; Esaki, Taito; Mitsugi, Kenji; Futami, Kitaro; Akashi, Koichi; Baba, Eishi

    2016-06-01

    Chemotherapy for advanced colitis-associated colorectal cancer (CAC) has been insufficiently evaluated. The goal of this study was to clarify the efficacy and safety of chemotherapy for CAC in Japan. CAC patients who were treated with chemotherapy between 2005 and 2015 were retrospectively examined. Twenty-nine patients (median age, 48 years; 23 men) were assessed. Eighteen patients had ulcerative colitis, and 11 had Crohn's disease. Three ulcerative colitis and four Crohn's disease patients were in the active disease phase. Primary tumors were located in the rectum/anus (n=16), the left colon (n=9), or the right colon (n=4). Palliative or adjuvant chemotherapy was performed in 13 and 16 patients, respectively. First-line palliative chemotherapy regimens were as follows: fluorouracil, leucovorin, and oxaliplatin (FOLFOX; n=6), FOLFOX+bevacizumab (n=3), and others (n=4). Adjuvant chemotherapy regimens were S-1 (n=7), oxaliplatin-based (n=4) and others (n=5). In palliative chemotherapy, the objective response rate was 15%, and the median progression-free survival and overall survival were 182 and 315 days, respectively. In adjuvant chemotherapy, the 5-year relapse-free survival rate was 78%. Grade 3/4 adverse events (AEs) were observed in 16 patients (55%). Active and remission inflammatory bowel disease patients suffered grade 3/4 nonhematological AEs at an incidence of 71 and 23%, respectively (P<0.01). Dose reduction was required in 11 patients (38%), eight of whom required it for hematological AEs. Adjuvant chemotherapy for CAC exhibited sufficient efficacy, whereas modest efficacy was shown for palliative chemotherapy for CAC. AEs, particularly nonhematological AEs, were closely associated with disease activity of colitis. PMID:26771865

  16. [Laparoscopic surgery and adjuvant therapy for colon cancer].

    PubMed

    Kubicka, Stefan; Geissler, Michael; Bruch, Hans-Peter; Trarbach, Tanja

    2009-01-01

    At present, about 10% of all oncological procedures in the colon are carried out laparoscopically. Acceptance is increasing. After successful R0 resection, the rule for stage III patients is: adjuvant therapy is indicated regardless of age. Regimens containing oxaliplatin should be used. If there are contraindications for oxaliplatin, then fluoropyrimidine monotherapy is indicated, with oral fluoropyrimidines (capecitabine) being given precedence over infusional schemes. The use of 5-FU bolus regimens is regarded as obsolete. For stage II, the following applies: If an adjuvant chemotherapy is planned in these patients on the basis of the QUASAR data, then fluoropyrimidine monotherapy (e. g. capecitabine) can be given. Since patients whose tumours show a high frequency of microsatellite instability (MSI) do not benefit from a fluoropyrimidine monotherapy, the MSI status should be determined before choosing therapy. PMID:19546595

  17. Resectable Cholangiocarcinoma: Reviewing the Role of Adjuvant Strategies

    PubMed Central

    Cidon, E. Una

    2016-01-01

    Cholangiocarcinoma is a very heterogeneous and rare group of neoplasms originating from the perihilar, intra-, or extrahepatic bile duct epithelium. It represents only 3% of gastrointestinal cancers, although their incidence is increasing as its mortality increases. Surgical resection is the only potentially curative option, but unfortunately the resectability rate is low. Overall, these malignancies have got a very poor prognosis with a five-year survival rate of 5–10%. Although the five-year survival rate increases to 25–30% in the cases amenable to surgery, only 10–40% of patients present with resectable disease. Therefore, it is necessary to optimize the benefit of adjuvant strategies after surgery to increase the rate of curability. This study reviewed the role of adjuvant chemotherapy in resectable bile duct cancers. PMID:27199577

  18. FAM172A is a tumor suppressor in colorectal carcinoma.

    PubMed

    Cui, Chunhui; Ye, Lili; Huang, Zonghai; Huang, Shuxin; Liu, Hao; Yu, Jinlong

    2016-05-01

    The present study was designed to elucidate the regulatory role of a novel protein FAM172A in carcinogenesis of colorectal carcinoma (CRC). Investigation of clinical samples using Western blotting showed that expression of FAM172A is significantly lower in cancerous tissues than in adjacent tissues. Furthermore, we constructed in vitro model for continuous overexpression and silencing of FAM172A with a retroviral vector system. FAM172A suppressed the proliferative and invasive potentials of LOVO cells as shown in MTT test, transwell migration assay, wound healing assay, 3D-culture morphologic study, and xenograft experiment. RT-PCR and Western blotting showed that FAM172A overexpression inhibited expressions of Cyclin D1, CDK2, MMP-2, MMP-9, PERK, elF2α, ATF6, XBP1, and GRP78, while FAM172A silencing induced their expressions. FAM172A might regulate ERS through PERK-elF2α, ATF6-XBP1-GRP78 signal pathway. The results implicated that FAM172A functioned as a tumor suppressor in colorectal carcinoma. PMID:26637224

  19. Time-to-administration in postoperative chemotherapy for colorectal cancer: does minimally-invasive surgery help?

    PubMed

    Amore Bonapasta, Stefano; Checcacci, Paolo; Guerra, Francesco; Mirasolo, Vita M; Moraldi, Luca; Ferrara, Angelo; Annecchiarico, Mario; Coratti, Andrea

    2016-06-01

    The optimal delay in the start of chemotherapy following rectal cancer surgery has not yet been identified. However, postponed adjuvant therapy has been proven to be connected with a significant survival detriment. We aimed to investigate whether the time to initiation of adjuvant treatment can be influenced by the application of minimally invasive surgery rather than traditional open surgery. By comprehensively evaluating the available inherent literature, several factors appear to be associated with delayed postoperative chemotherapy. Some of them are strictly related to surgical short-term outcomes. Laparoscopy results in shortened length of hospital stay, reduced surgical morbidity and lower rate of wound infection compared to conventional surgery. Probably due to such advantages, the application of minimally-invasive surgery to treat rectal malignancies seems to impact favorably the possibility to start adjuvant chemotherapy within an adequate timeframe following surgical resection, with potential improvement in patient survival. PMID:26976732

  20. Postoperative adjuvant therapy of breast cancer. Oncology Overview

    SciTech Connect

    Not Available

    1984-12-01

    Oncology Overviews are a service of the International Cancer Research Data Bank (ICRDB) Program of the National Cancer Institute, intended to facilitate and promote the exchange of information between cancer scientists by keeping them aware of literature related to their research being published by other laboratories throughout the world. Each Oncology Overview represents a survey of the literature associated with a selected area of cancer research. It contains abstracts of articles which have been selected and organized by researchers associated with the field. Contents: Postoperative chemotherapy; Postoperative radiotherapy; Postoperative hormone therapy; Postoperative immunotherapy and chemoimmunotherapy; Postoperative multimodal therapy; Prognostic factors in postoperative adjuvant therapy.

  1. Using antimicrobial adjuvant therapy in cancer treatment: a review

    PubMed Central

    2012-01-01

    Recent clinical and pre-clinical data demonstrate that adjuvant antimicrobial therapy is beneficial in cancer treatment. There could be several reasons for this effect, which include treating cancer associated bacteria and viruses, prophylaxis of post-chemotherapy infections due to immunosuppression, and antiproliferative effect of certain antimicrobials. Targeting cancer associated viruses and bacteria with antimicrobial agents is currently used for gastric, cervical, hematopoietic, liver and brain cancer. However this treatment is effective only in combination with conventional therapies. Antimicrobials can also have a direct antiproliferative and cytotoxic effect, and can cause apoptosis. Moreover, some antimicrobials are known to be helpful in overcoming side effects of drugs commonly used in cancer treatment. Chemotherapy related bacteremia and neutropenia can be overcome by the appropriately timed use of antimicrobials. This review summarizes the data on the effects of antivirals and antibiotics on cancer treatment and describes their mechanisms. PMID:23164412

  2. Adjuvant Therapeutic Modalities in Primary Small Cell Carcinoma of Esophagus Patients

    PubMed Central

    Zou, Bingwen; Li, Tao; Zhou, Qiang; Ma, Daiyuan; Chen, Yongshun; Huang, Meijuan; Peng, Feng; Xu, Yong; Zhu, Jiang; Ding, Zhenyu; Zhou, Lin; Wang, Jin; Ren, Li; Yu, Min; Gong, Youling; Li, Yanying; Chen, Longqi; Lu, You

    2016-01-01

    Abstract To evaluate the treatment pattern and survival of patients receiving radical resection for primary small cell carcinoma of the esophagus (PSCCE). This retrospective study included 150 patients who received radical resection of PSCCE. Data were retrieved from 4 centers in Western China. Thirty-nine of 150 patients received postoperative chemo-radiotherapy, 62 received postoperative chemotherapy, and 49 received radical resection only. The median radiation dosage was 50 Gy. The chemotherapeutic regimen was platinum-based and lasted for 2 to 6 cycles (median, 3). Median disease-free survival (mDFS) and overall survival (mOS) were 12.0 and 18.3 months, respectively. Subgroup analysis revealed that postoperative therapy did not improve survival in limited stage I (LSI) disease, whereas postoperative chemotherapy improved survival in limited stage II (LSII) disease. Relative to chemotherapy alone, chemoradiotherapy did not improve survival in patients with completely resected LSII disease. A multivariate analysis indicated an association of no postoperative chemotherapy with shorter DFS (P = 0.050) and OS (P = 0.010). Higher lymph node stage and length of disease longer than 3 cm were poor prognostic factors for both DFS and OS. Adjuvant chemotherapy improves survival in PSCCE patients with completely resected LSII disease. Adjuvant treatment with postoperative chemotherapy alone or postoperative chemo-radiotherapy does not increase survival in completely resected LSI disease. PMID:27124057

  3. Innate immunity and adjuvants.

    PubMed

    Akira, Shizuo

    2011-10-12

    Innate immunity was for a long time considered to be non-specific because the major function of this system is to digest pathogens and present antigens to the cells involved in acquired immunity. However, recent studies have shown that innate immunity is not non-specific, but is instead sufficiently specific to discriminate self from pathogens through evolutionarily conserved receptors, designated Toll-like receptors (TLRs). Indeed, innate immunity has a crucial role in early host defence against invading pathogens. Furthermore, TLRs were found to act as adjuvant receptors that create a bridge between innate and adaptive immunity, and to have important roles in the induction of adaptive immunity. This paradigm shift is now changing our thinking on the pathogenesis and treatment of infectious, immune and allergic diseases, as well as cancers. Besides TLRs, recent findings have revealed the presence of a cytosolic detector system for invading pathogens. I will review the mechanisms of pathogen recognition by TLRs and cytoplasmic receptors, and then discuss the roles of these receptors in the development of adaptive immunity in response to viral infection. PMID:21893536

  4. Innate immunity and adjuvants

    PubMed Central

    Akira, Shizuo

    2011-01-01

    Innate immunity was for a long time considered to be non-specific because the major function of this system is to digest pathogens and present antigens to the cells involved in acquired immunity. However, recent studies have shown that innate immunity is not non-specific, but is instead sufficiently specific to discriminate self from pathogens through evolutionarily conserved receptors, designated Toll-like receptors (TLRs). Indeed, innate immunity has a crucial role in early host defence against invading pathogens. Furthermore, TLRs were found to act as adjuvant receptors that create a bridge between innate and adaptive immunity, and to have important roles in the induction of adaptive immunity. This paradigm shift is now changing our thinking on the pathogenesis and treatment of infectious, immune and allergic diseases, as well as cancers. Besides TLRs, recent findings have revealed the presence of a cytosolic detector system for invading pathogens. I will review the mechanisms of pathogen recognition by TLRs and cytoplasmic receptors, and then discuss the roles of these receptors in the development of adaptive immunity in response to viral infection. PMID:21893536

  5. High Risk Stage 2 and Stage 3 Colon Cancer, Predictors of Recurrence and Effect of Adjuvant Therapy in a Nonselected Population

    PubMed Central

    van Eeghen, Elmer E.; Bakker, Sandra D.; van Bochove, Aart; Loffeld, Ruud J. L. F.

    2015-01-01

    Patients with stage 2 and stage 3 colon cancer often are treated with adjuvant chemotherapy. However, patients seen in daily practice have more comorbidity than those enrolled in clinical trials. This study aims to evaluate prognostic factors for recurrence and to ascertain the benefit of adjuvant chemotherapy on recurrence-free survival (RFS) of patients in a nonselected population. Furthermore, the impact of relative dose intensity (RDI) of adjuvant therapy on RFS is examined. Chart review was performed for 243 consecutive patients diagnosed and treated at a single center for stage 2 and stage 3 colon cancer from 2002 to 2008. Adjuvant chemotherapy was administered to 66 patients. Median overall survival (OS) was 5.84 years and median RFS was 5.37 years. For stage 2 disease, patients treated with or without adjuvant therapy had a median RFS of 5.49 and 5.73, respectively (p = ns). For stage 3 disease, median RFS rates were 5.08 and 1.19, respectively (p = 0.084). Overall RDI of oxaliplatin based chemotherapy higher than median was associated with increased RFS (p = 0.045). In conclusion, adjuvant therapy did not significantly increase recurrence-free survival. This could be the result of comorbidity in patients. Relative dose intensity of oxaliplatin based therapy is associated with RFS.

  6. Advances in adjuvant systemic therapy for non-small-cell lung cancer.

    PubMed

    Leong, David; Rai, Rajat; Nguyen, Brandon; Lee, Andrew; Yip, Desmond

    2014-10-10

    Non-small-cell lung cancer remains a leading cause of death around the world. For most cases, the only chance of cure comes from resection for localised disease, however relapse rates remain high following surgery. Data has emerged over recent years regarding the utility of adjuvant chemotherapy for improving disease-free and overall survival of patients following curative resection. This paper reviews the clinical trials that have been conducted in this area along with the studies integrating radiation therapy in the adjuvant setting. The role of prognostic gene signatures are reviewed as well as ongoing clinical trials including those incorporating biological or targeted therapies. PMID:25302167

  7. Docetaxel as adjuvant and neoadjuvant treatment for patients with breast cancer.

    PubMed

    Heys, Steven D; Sarkar, Tarun; Hutcheon, Andrew W

    2004-10-01

    Developments in the role of adjuvant and neoadjuvant chemotherapy for the treatment of patients with breast cancer have focused on the taxes, in particular, docetaxel. This paper discusses the rationale for the introduction of docetaxel into the management of patients following surgery and also its role in those patients with locally-advanced disease, focussing on key clinical trials. The addition of docetaxel to standard adjuvant chemotherapeutic regimens does seem to result in an increased survival in some patients with early-stage disease. In the neoadjuvant setting, the addition of docetaxel to standard regimens does increase pathological response rates, which is a surrogate marker of eventual outcome. PMID:15461550

  8. [Chemotherapy of gastrointestinal tumors (review of the literature)].

    PubMed

    Mayr, A C

    1978-12-01

    There exist no common recommendations for palliative therapy of gastrointestinal cancer. Fluorouracil has been used for a long time, remission rates reported range from 0% to 80%. In larger series they figure about 20% but without prolongation of survival in responders. Although this drug is used for 20 years optimal dose and timing is still unknown. By combination of fluorouracil with other drugs remission rates were improved and in responders survival was prolonged (mitomycin C and/or adriamycin in gastric cancer, methyl-CCNU in colorectal cancer). The results of adjuvant chemotherapy of gastrointestinal cancer are contradictory, the routine usage is not recommendable. Adjuvant as well as palliative chemotherapy must be improved by controlled clinical trials. PMID:83561

  9. Classification of Laser Vaccine Adjuvants

    PubMed Central

    Kashiwagi, Satoshi; Brauns, Timothy; Poznansky, Mark C

    2016-01-01

    An immunologic adjuvant, which enhances the magnitude and quality of immune responses to vaccine antigens, has become an essential part of modern vaccine practice. Chemicals and biologicals have been typically used for this purpose, but there are an increasing number of studies that are being conducted on the vaccine adjuvant effect of laser light on the skin. Currently, four different types or classes of laser devices have been shown to systemically enhance immune responses to intradermal vaccination: ultra-short pulsed lasers, non-pulsed lasers, non-ablative fractional lasers and ablative fractional lasers. Aside from involving the application of laser light to the skin in a manner that minimizes discomfort and damage, each type of laser vaccine adjuvant involves emission parameters, modes of action and immunologic adjuvant effects that are quite distinct from each other. This review provides a summary of the four major classes of “laser vaccine adjuvant” and clarifies and resolves their characteristics as immunologic adjuvants. These aspects of each adjuvant’s properties will ultimately help define which laser would be most efficacious in delivering a specific clinical benefit with a specific vaccine. PMID:27104047

  10. Production and Characterization of Monoclonal Antibodies against Human Nuclear Protein FAM76B.

    PubMed

    Zheng, Xiaojing; Li, Yanqing; Zhao, Junli; Wang, Dongyang; Xia, Haibin; Mao, Qinwen

    2016-01-01

    Human FAM76B (hFAM76B) is a 39 kDa protein that contains homopolymeric histidine tracts, a targeting signal for nuclear speckles. FAM76B is highly conserved among different species, suggesting that it may play an important physiological role in normal cellular functions. However, a lack of appropriate tools has hampered study of this potentially important protein. To facilitate research into the biological function(s) of FAM76B, murine monoclonal antibodies (MAbs) against hFAM76B were generated by using purified, prokaryotically expressed hFAM76B protein. Six strains of MAbs specific for hFAM76B were obtained and characterized. The specificity of MAbs was validated by using FAM76B-/- HEK 293 cell line. Double immunofluorescence followed by laser confocal microscopy confirmed the nuclear speckle localization of hFAM76B, and the specific domains recognized by different MAbs were further elucidated by Western blot. Due to the high conservation of protein sequences between mouse and human FAM76B, MAbs against hFAM76B were shown to react with mouse FAM76B (mFAM76B) specifically. Lastly, FAM76B was found to be expressed in the normal tissues of most human organs, though to different extents. The MAbs produced in this study should provide a useful tool for investigating the biological function(s) of FAM76B. PMID:27018871

  11. Production and Characterization of Monoclonal Antibodies against Human Nuclear Protein FAM76B

    PubMed Central

    Zheng, Xiaojing; Li, Yanqing; Zhao, Junli; Wang, Dongyang; Xia, Haibin; Mao, Qinwen

    2016-01-01

    Human FAM76B (hFAM76B) is a 39 kDa protein that contains homopolymeric histidine tracts, a targeting signal for nuclear speckles. FAM76B is highly conserved among different species, suggesting that it may play an important physiological role in normal cellular functions. However, a lack of appropriate tools has hampered study of this potentially important protein. To facilitate research into the biological function(s) of FAM76B, murine monoclonal antibodies (MAbs) against hFAM76B were generated by using purified, prokaryotically expressed hFAM76B protein. Six strains of MAbs specific for hFAM76B were obtained and characterized. The specificity of MAbs was validated by using FAM76B-/- HEK 293 cell line. Double immunofluorescence followed by laser confocal microscopy confirmed the nuclear speckle localization of hFAM76B, and the specific domains recognized by different MAbs were further elucidated by Western blot. Due to the high conservation of protein sequences between mouse and human FAM76B, MAbs against hFAM76B were shown to react with mouse FAM76B (mFAM76B) specifically. Lastly, FAM76B was found to be expressed in the normal tissues of most human organs, though to different extents. The MAbs produced in this study should provide a useful tool for investigating the biological function(s) of FAM76B. PMID:27018871

  12. EGFR phosphorylates FAM129B to promote Ras activation

    PubMed Central

    Ji, Haitao; Lee, Jong-Ho; Wang, Yugang; Pang, Yilin; Zhang, Tao; Xia, Yan; Zhong, Lianjin; Lyu, Jianxin; Lu, Zhimin

    2016-01-01

    Ras GTPase-activating proteins (GAPs) are important regulators for Ras activation, which is instrumental in tumor development. However, the mechanism underlying this regulation remains elusive. We demonstrate here that activated EGFR phosphorylates the Y593 residue of the protein known as family with sequence similarity 129, member B (FAM129B), which is overexpressed in many types of human cancer. FAM129B phosphorylation increased the interaction between FAM129B and Ras, resulting in reduced binding of p120-RasGAP to Ras. FAM129B phosphorylation promoted Ras activation, increasing ERK1/2- and PKM2-dependent β-catenin transactivation and leading to the enhanced glycolytic gene expression and the Warburg effect; promoting tumor cell proliferation and invasion; and supporting brain tumorigenesis. Our studies unearthed a novel and important mechanism underlying EGFR-mediated Ras activation in tumor development. PMID:26721396

  13. The role of adjuvant radiation in endometrial cancer.

    PubMed

    Diavolitsis, Virginia; Boyle, John; Singh, Diljeet K; Small, William

    2009-04-15

    Endometrial cancer treatment ideally begins with a staging procedure including abdominopelvic washing, total abdominal hysterectomy, bilateral salpingo-oophorectomy, and lymph node evaluation. Recommendations for postoperative adjuvant radiotherapy are determined by recurrence risk. Patients who have undergone staging and have early stage I disease and an absence of high-risk features for recurrence generally are treated with surgery alone. Intermediate-risk patients--those with high-risk stage I disease and some stage II patients--may benefit from adjuvant radiation therapy. Several randomized trials show that radiation therapy improves locoregional control among intermediate-risk patients. The optimal type of radiation therapy, whether vaginal brachytherapy or whole-pelvic radiation therapy, remains undetermined, though treatment decision can be guided by risk factors not encompassed by the current staging system. Patients with high-risk stage II disease and stage III disease generally receive external-beam radiotherapy, often in combination with chemotherapy. Chemotherapy alone in advanced-stage patients is a consideration, given the results of the Gynecologic Oncology Group (GOG)-122 trial. PMID:19476264

  14. Cytoreductive surgery plus chemotherapy versus chemotherapy alone for recurrent epithelial ovarian cancer

    PubMed Central

    Galaal, Khadra; Naik, Raj; Bristow, Robert E; Patel, Amit; Bryant, Andrew; Dickinson, Heather O

    2014-01-01

    Background Most women with advanced epithelial ovarian cancer will ultimately develop recurrent disease after completion of initial treatment with primary surgery and adjuvant chemotherapy. Secondary cytoreductive surgery may have survival benefits in selected patients. However, a number of chemotherapeutic agents are active in recurrent ovarian cancer and the standard treatment of patients with recurrent ovarian cancer remains poorly defined. Objectives To evaluate the effectiveness and safety of secondary surgical cytoreduction and chemotherapy compared to chemotherapy alone for women with recurrent epithelial ovarian cancer. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, The Cochrane Register of Controlled Trials, (CENTRAL) Issue 1 2009, MEDLINE and EMBASE up to February 2009. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of review articles and contacted experts in the field. Selection criteria We searched for RCTs, quasi-randomised trials and non-randomised studies that compared secondary cytoreductive surgery and chemotherapy to chemotherapy alone in women with recurrent epithelial ovarian cancer. Data collection and analysis Three reviewers independently assessed whether potentially relevant studies met the inclusion criteria. No trials were found and therefore no data were analysed. Main results The search strategy identified 1431 unique references of which all were excluded on the basis of title and abstract. Authors’ conclusions We found no evidence from RCTs to inform decisions about secondary surgical cytoreduction and chemotherapy compared to chemotherapy alone for women with recurrent epithelial ovarian cancer. Ideally, a large randomised controlled trial or, at the very least, well designed non-randomised studies that use multivariate analysis to adjust for baseline imbalances are needed to compare these treatment modalities. The results of the ongoing RCT AGO

  15. Chemokines as Cancer Vaccine Adjuvants

    PubMed Central

    Bobanga, Iuliana D.; Petrosiute, Agne; Huang, Alex Y.

    2013-01-01

    We are witnessing a new era of immune-mediated cancer therapies and vaccine development. As the field of cancer vaccines advances into clinical trials, overcoming low immunogenicity is a limiting step in achieving full success of this therapeutic approach. Recent discoveries in the many biological roles of chemokines in tumor immunology allow their exploitation in enhancing recruitment of antigen presenting cells (APCs) and effector cells to appropriate anatomical sites. This knowledge, combined with advances in gene therapy and virology, allows researchers to employ chemokines as potential vaccine adjuvants. This review will focus on recent murine and human studies that use chemokines as therapeutic anti-cancer vaccine adjuvants. PMID:24967094

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

    PubMed Central

    Isakoff, Steven J.

    2010-01-01

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

  17. Identification of FAM3D as a new endogenous chemotaxis agonist for the formyl peptide receptors.

    PubMed

    Peng, Xinjian; Xu, Enquan; Liang, Weiwei; Pei, Xiaolei; Chen, Dixin; Zheng, Danfeng; Zhang, Yang; Zheng, Can; Wang, Pingzhang; She, Shaoping; Zhang, Yan; Ma, Jing; Mo, Xiaoning; Zhang, Yingmei; Ma, Dalong; Wang, Ying

    2016-05-01

    The family with sequence similarity 3 (FAM3) gene family is a cytokine-like gene family with four members FAM3A, FAM3B, FAM3C and FAM3D. In this study, we found that FAM3D strongly chemoattracted human peripheral blood neutrophils and monocytes. To identify the FAM3D receptor, we used chemotaxis, receptor internalization, Ca(2+) flux and radioligand-binding assays in FAM3D-stimulated HEK293 cells that transiently expressed formyl peptide receptor (FPR)1 or FPR2 to show that FAM3D was a high affinity ligand of these receptors, both of which were highly expressed on the surface of neutrophils, and monocytes and macrophages. After being injected into the mouse peritoneal cavity, FAM3D chemoattracted CD11b+ Ly6G+ neutrophils in a short time. In response to FAM3D stimulation, phosphorylated ERK1/2 and phosphorylated p38 MAPK family proteins were upregulated in the mouse neutrophils, and this increase was inhibited upon treatment with an inhibitor of FPR1 or FPR2. FAM3D has been reported to be constitutively expressed in the gastrointestinal tract. We found that FAM3D expression increased significantly during colitis induced by dextran sulfate sodium. Taken together, we propose that FAM3D plays a role in gastrointestinal homeostasis and inflammation through its receptors FPR1 and FPR2. PMID:26966188

  18. Drift reduction with drift control adjuvants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Numerous drift reduction adjuvants and spray deposition aids are available to applicators of crop production and protection chemicals. Performance of many of the newly introduced drift control adjuvants has not been well documented for aerial application. Five new drift control adjuvants were sele...

  19. Spray drift mitigation with spray mix adjuvants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Numerous drift reduction adjuvants and spray deposition aids are available to applicators of crop production and protection chemicals. Performance of many of the newly introduced drift control adjuvants has not been well documented for aerial application. Four new drift control adjuvants were sele...

  20. Drift reduction with drift control adjuvants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Numerous drift reduction adjuvants and spray deposition aids are available to applicators of crop production and protection chemicals. Performance of many of the newly introduced drift control adjuvants has not been well documented for aerial application. Four new drift control adjuvants were sele...

  1. QS-21: a potent vaccine adjuvant

    Technology Transfer Automated Retrieval System (TEKTRAN)

    QS-21 is an potent adjuvant derived from the bark of a Chilean tree, Quillaja saponaria. One of the advantages of this adjuvant is that it promotes a balanced humoral and cell-mediaed immune response and can be widely applicable to a variety of vaccines. This adjuvant has used for some veterinary va...

  2. Selecting a specific pre- or postoperative adjuvant therapy for individual patients with operable gastric cancer.

    PubMed

    Briasoulis, Evangelos; Liakakos, Theodore; Dova, Lefkothea; Fatouros, Michael; Tsekeris, Pericles; Roukos, Dimitrios H; Kappas, Angelos M

    2006-06-01

    Although the very high locoregional recurrence rates reported with limited D0/D1 surgery can be reduced with extended D2 gastrectomy for operable gastric cancer, overall relapse and survival rates remain poor and can only be improved with adequate perioperative adjuvant treatment. However, despite intensive research, no regimen has been established as standard. Meta-analyses have demonstrated a marginal survival benefit with adjuvant chemotherapy. Two recent large randomized trials for operable gastric cancer, the MAGIC trial and the INT-0116 trial, provide evidence that some patients may benefit from perioperative chemotherapy and chemoradiation, respectively. However, while both trials suggest an overall survival benefit with adjuvant treatment, they don't provide the harm-benefit ratio for specific subsets of patients wih different extent of surgery (D1 or D2) and tumor stage (early [T1,2]/advanced [T3,4]). This lack of evidence complicates current therapeutic adjuvant decisions. Estimating the risk of local and distant recurrence (high, moderate or low) after D1 or D2 surgery in various tumor stages and the expected harm-benefit ratio, the authors provide useful information for decisions on adjuvant chemotherapy with or withour radiotherapy in individual patients. Research on newer cytotoxic and targeted agents may improve treatment efficacy. Simultaneously, advances with microarray-based gene-expression profiling signatures may improve individualized treatment decisions. However, the validation and translation of these genomic classifiers as biomarkers into a completed 'bench-to-bedside' cycle for tailoring treatment to individuals is a major challenge and limits inflated expectations. PMID:16761937

  3. Adjuvant radiotherapy in the treatment of gall bladder carcinoma: What is the current evidence.

    PubMed

    Mallick, Supriya; Benson, Rony; Haresh, K P; Julka, P K; Rath, G K

    2016-03-01

    Gall bladder carcinoma (GBC) is considered the fifth most common one of the most aggressive gastro intestinal tract malignancies. Owing to their large incidence randomised controlled trials have hardly been conducted to look into their optimum treatment. Over the years surgical resection has been considered the only curative treatment of these tumors. However, the outcome still remains guarded. The predominant pattern of failure is loco-regional followed by systemic. Hence, local adjuvant radiation has been used by different institutes with concurrent and adjuvant chemotherapy. The large retrospective series with their limitations showed improved survival in patients with regional spread or tumors infiltrating the liver when treated with adjuvant radiotherapy. In the present era with modern radiation techniques and target delineation radiation may further improve upon the impact without adding to the toxicity profile. Hence, radiation in gall bladder cancer needs a relook to optimize treatment outcome of such aggressive disease. PMID:26265290

  4. Preliminary Experience with Locoregional Intraarterial Chemotherapy of Uterine Cervical or Endometrial Cancer Using the Peripheral Implantable Port System (PIPS{sup TM}): A Feasibility Study

    SciTech Connect

    Strecker, Ernst-Peter; Heber, Ralf; Boos, Irene; Goettmann, Dieter; Heinrich, Dirk

    2003-04-15

    The purpose of this study was to assess the suitability of a percutaneously implantable catheter port system (PIPS)for repeated intraarterial locoregional chemotherapy (ILC) for cervical and endometrial carcinoma. In 30 patients with advanced, recurrent, or high-risk cervical (n 23) or endometrial(n = 7) carcinoma, PIPS for ILC was implanted via a femoral access, the catheter localized in the infrarenal abdominal aorta. Chemotherapy was performed adjuvantly after surgery(n = 14) or neo-adjuvantly to enable surgery, or for palliation (n = 16). Port implantation, catheter placement, and repeated port puncture was uneventful in all patients.Complications included catheter dislocation (n = 1),catheter thrombosis (n = 2), subcutaneous infection(n = 1), port-bed skin atrophy (n = 1),requiring port explantation in 3 patients. At 2 years follow-up,complete remission was observed in 7/14 patients with adjuvant chemotherapy, partial remission in 3/14. Successful down-staging could be achieved in 4/8 patients with neo-adjuvant chemotherapy. The PIPS is suitable for repeated ILC which may be a valuable method for pre- and post-surgical therapy of advanced or high-risk cervical and endometrial cancer, for adjuvant chemotherapy as well as neo-adjuvantly for down-staging, or for palliation.

  5. SNRFCB: sub-network based random forest classifier for predicting chemotherapy benefit on survival for cancer treatment.

    PubMed

    Shi, Mingguang; He, Jianmin

    2016-04-22

    Adjuvant chemotherapy (CTX) should be individualized to provide potential survival benefit and avoid potential harm to cancer patients. Our goal was to establish a computational approach for making personalized estimates of the survival benefit from adjuvant CTX. We developed Sub-Network based Random Forest classifier for predicting Chemotherapy Benefit (SNRFCB) based gene expression datasets of lung cancer. The SNRFCB approach was then validated in independent test cohorts for identifying chemotherapy responder cohorts and chemotherapy non-responder cohorts. SNRFCB involved the pre-selection of gene sub-network signatures based on the mutations and on protein-protein interaction data as well as the application of the random forest algorithm to gene expression datasets. Adjuvant CTX was significantly associated with the prolonged overall survival of lung cancer patients in the chemotherapy responder group (P = 0.008), but it was not beneficial to patients in the chemotherapy non-responder group (P = 0.657). Adjuvant CTX was significantly associated with the prolonged overall survival of lung cancer squamous cell carcinoma (SQCC) subtype patients in the chemotherapy responder cohorts (P = 0.024), but it was not beneficial to patients in the chemotherapy non-responder cohorts (P = 0.383). SNRFCB improved prediction performance as compared to the machine learning method, support vector machine (SVM). To test the general applicability of the predictive model, we further applied the SNRFCB approach to human breast cancer datasets and also observed superior performance. SNRFCB could provide recurrent probability for individual patients and identify which patients may benefit from adjuvant CTX in clinical trials. PMID:26864276

  6. Administration of Concurrent Vaginal Brachytherapy During Chemotherapy for Treatment of Endometrial Cancer

    SciTech Connect

    Nagar, Himanshu; Boothe, Dustin; Parikh, Amar; Yondorf, Menachem; Parashar, Bhupesh; Gupta, Divya; Holcomb, Kevin; Caputo, Thomas; Chao, K. S. Clifford; Nori, Dattatreyudu; Wernicke, A. Gabriella

    2013-11-15

    Purpose: To evaluate the tolerability and toxicity of administering vaginal brachytherapy (VB) concurrently during chemotherapy compared with the sequential approach for patients with endometrial cancer. Methods and Materials: A retrospective analysis of 372 surgically staged patients with endometrial cancer American Joint Committee on Cancer 2009 stages I to IV treated with adjuvant postoperative radiation therapy (RT) at our institution from 2001 to 2012 was conducted. All patients received VB + external beam RT (EBRT) + 6 cycles of adjuvant carboplatin- and paclitaxel-based chemotherapy. The VB mean dose was 15.08 Gy (range, 15-20 Gy), with 3 to 4 weekly applications, and the EBRT mean dose was 45 Gy delivered with 3-dimensional or intensity modulated RT techniques. Hematologic, gastrointestinal (GI), and genitourinary (GU) toxicities were assessed by Common Toxicity Criteria (CTC) and compared between sequential and concurrent chemotherapy and VB schedules. Results: Among patients who received RT and adjuvant chemotherapy, 180 of 372 patients (48%) received RT sandwiched between cycles 3 and 4 of chemotherapy. A separate group of 192 patients (52%) were treated with VB during the first 3 cycles of chemotherapy, with a weekly application on nonchemotherapy days, and received the EBRT portion in a sandwiched fashion. Patients treated with VB during chemotherapy had a decreased overall treatment time by 4 weeks (P<.001; 95% confidence interval: 3.99-4.02) and sustained no difference in CTC-graded acute hematologic, GI, or GU toxicities in comparison with the patients treated with VB and chemotherapy in a sequential manner (P>.05). CTC grade 3 or 4 hematologic, GI, and GU toxicities were zero. Conclusions: VB during chemotherapy is well tolerated, decreases overall treatment time, and does not render more toxicity than the sequential regimen.

  7. Adjuvant Therapy for Thymic Carcinoma – A Decade of Experience in a Taiwan National Teaching Hospital

    PubMed Central

    Tseng, Yen-Han; Lin, Yi-Hsuan; Tseng, Yen-Chiang; Lee, Yu-Chin; Wu, Yu-Chung; Hsu, Wen-Hu; Yen, Sang-Hue; Whang-Peng, Jacqueline; Chen, Yuh-Min

    2016-01-01

    Background Thymic carcinomas are rare tumors for which surgical resection is the first treatment of choice. The role of adjuvant treatment after surgery is unknown because of limited available data. The present study evaluated the efficacy of post-surgery adjuvant chemotherapy or radiotherapy in patients with thymic carcinoma. Methods To evaluate the role of adjuvant therapy in patients with thymic carcinoma, we retrospectively reviewed the records of patients with thymic carcinoma who were diagnosed and treated between 2004 and 2014. Results Among 78 patients with thymic carcinoma, 30 patients received surgical resection. Progression-free survival (PFS) and overall survival (OS) were significantly longer among these patients than among patients who received other treatments (PFS: 88.4 months vs 9.1 months, p<0.001; OS: 134.9 months vs 60.9 months; p = 0.003). Patients with stage III thymic carcinoma who received surgery had a longer OS than patients who did not receive surgery (70.1 months vs 23.9 months; p = 0.017, n = 11). Among 47 patients with stage IV carcinoma, 12 patients who received an extended thymothymectomy had a longer PFS than 35 patients who did not receive surgery (18.9 months vs 8.7 months; p = 0.029). Among 30 patients (with stage I- IV carcinoma) who received primary lesion surgery, 19 patients received an R0 resection and 9 patients of the 19 patients received adjuvant radiotherapy. These patients had longer PFS (50.3 months) than 2 patients who received adjuvant chemotherapy (5.9 months) or 4 patients who received concurrent chemoradiotherapy (7.5 months) after surgery (p = 0.003). Conclusions Surgical resection should be considered for patients with thymic carcinoma, even for patients with locally advanced or stage IV carcinoma. Adjuvant radiotherapy resulted in a better PFS after R0 resection. PMID:26757052

  8. EGFR-TKIs in adjuvant treatment of lung cancer: to give or not to give?

    PubMed Central

    Milovancev, Aleksandar; Stojsic, Vladimir; Zaric, Bojan; Kovacevic, Tomi; Sarcev, Tatjana; Perin, Branislav; Zarogoulidis, Konstantinos; Tsirgogianni, Katerina; Freitag, Lutz; Darwiche, Kaid; Tsavlis, Drosos; Zissimopoulos, Athanasios; Stratakos, Grigoris; Zarogoulidis, Paul

    2015-01-01

    Epidermal growth factor receptor-tyrosine-kinase inhibitors (EGFR-TKIs) brought a significant revolution in the treatment of non-small-cell lung cancer (NSCLC). In a short period of time, EGFR-TKIs became the standard of treatment for mutation-positive, advanced stage non-squamous NSCLC. In recent years, second- and third-generation EGFR-TKIs are emerging, further widening the clinical use. However, the question of EGFR-TKIs efficiency in the treatment of early stage NSCLC still remains open. Early clinical trials failed to approve the use of EGFR-TKIs in adjuvant setting. The majority of these early trials were performed in unselected NSCLC populations and without standardized biomarker identification. One should certainly not rely solely on these results and dismiss the use of EGFR-TKIs as adjuvant therapy. Many important questions are still unanswered. Most important issues such as stage heterogeneity (IA–IIIA), timing (after or concomitantly with chemotherapy), and type of administration (monotherapy or combination) need to be answered in near future. Adjuvant TKIs in the treatment of lung cancer might offer significant number of advancements. Having in mind the significant duration of response observed in advance disease setting, there could be place for prolongation of response in adjuvant setting potentially, leading to improvement in survival. TKIs could offer less-toxic adjuvant treatment with better efficiency than chemotherapy. However, there is a chronic lack of randomized controlled trials in this field, leading to inability to draw any scientifically sound conclusion with regard to the adjuvant treatment. For now, the use of EGFR-TKIs outside clinical trial setting is not recommended. The purpose of this review is to evaluate current and available data. PMID:26508876

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

    SciTech Connect

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

    1983-01-01

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

  10. Trastuzumab after Chemotherapy Is Effective in HER2-Positive Breast Cancer

    Cancer.gov

    Treatment with trastuzumab for 1 year following standard chemotherapy improved disease-free survival in women with HER2-positive early breast cancer, according to 4-year follow-up results of the Herceptin Adjuvant (HERA) trial reported February 25, 2011,

  11. Chemotherapy in Prostate Cancer.

    PubMed

    Hurwitz, Michael

    2015-10-01

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

  12. The association of adjuvant therapy with survival at the population level following pancreatic adenocarcinoma resection

    PubMed Central

    Kagedan, Daniel J.; Raju, Ravish S.; Dixon, Matthew E.; Shin, Elizabeth; Li, Qing; Liu, Ning; Elmi, Maryam; El-Sedfy, Abraham; Paszat, Lawrence; Kiss, Alexander; Earle, Craig C.; Mittmann, Nicole; Coburn, Natalie G.

    2016-01-01

    Background Using a retrospective observational cohort approach, the overall survival (OS) following curative-intent resection of pancreatic adenocarcinoma (PC) was defined at the population level according to adjuvant treatment, and predictors of OS were identified. Methods Patients undergoing resection of PC in the province of Ontario between 2005 and 2010 were identified using the provincial cancer registry, and linked to databases that include all treatments received and outcomes experienced in the province. Pathology reports were abstracted for staging and margin status. Patients were identified as having received chemotherapy (CT), chemoradiation therapy (CRT), or no adjuvant treatment (NAT). Kaplan–Meier survival analysis of patients surviving ≥6 months was performed, and predictors of OS identified by log-rank test. Cox multivariable analysis was used to define independent predictors of OS. Results Among the 473 patients undergoing PC resection, the median survival was 17.8 months; for the 397 who survived ≥6 months following surgery, the 5-year OS for the CT, CRT, and NAT groups was 21%, 16%, and 17%, respectively (p = 0.584). Lymph node-negative patients demonstrated improved OS associated with chemotherapy on multivariable analysis (HR = 2.20, 95% CI = 1.25–3.83 for NAT vs. CT). Conclusions Following PC resection, only patients with negative lymph nodes demonstrated improved OS associated with adjuvant chemotherapy. PMID:27037203

  13. Chemotherapy-induced antitumor immunity requires formyl peptide receptor 1.

    PubMed

    Vacchelli, Erika; Ma, Yuting; Baracco, Elisa E; Sistigu, Antonella; Enot, David P; Pietrocola, Federico; Yang, Heng; Adjemian, Sandy; Chaba, Kariman; Semeraro, Michaela; Signore, Michele; De Ninno, Adele; Lucarini, Valeria; Peschiaroli, Francesca; Businaro, Luca; Gerardino, Annamaria; Manic, Gwenola; Ulas, Thomas; Günther, Patrick; Schultze, Joachim L; Kepp, Oliver; Stoll, Gautier; Lefebvre, Céline; Mulot, Claire; Castoldi, Francesca; Rusakiewicz, Sylvie; Ladoire, Sylvain; Apetoh, Lionel; Bravo-San Pedro, José Manuel; Lucattelli, Monica; Delarasse, Cécile; Boige, Valérie; Ducreux, Michel; Delaloge, Suzette; Borg, Christophe; André, Fabrice; Schiavoni, Giovanna; Vitale, Ilio; Laurent-Puig, Pierre; Mattei, Fabrizio; Zitvogel, Laurence; Kroemer, Guido

    2015-11-20

    Antitumor immunity driven by intratumoral dendritic cells contributes to the efficacy of anthracycline-based chemotherapy in cancer. We identified a loss-of-function allele of the gene coding for formyl peptide receptor 1 (FPR1) that was associated with poor metastasis-free and overall survival in breast and colorectal cancer patients receiving adjuvant chemotherapy. The therapeutic effects of anthracyclines were abrogated in tumor-bearing Fpr1(-/-) mice due to impaired antitumor immunity. Fpr1-deficient dendritic cells failed to approach dying cancer cells and, as a result, could not elicit antitumor T cell immunity. Experiments performed in a microfluidic device confirmed that FPR1 and its ligand, annexin-1, promoted stable interactions between dying cancer cells and human or murine leukocytes. Altogether, these results highlight the importance of FPR1 in chemotherapy-induced anticancer immune responses. PMID:26516201

  14. Vaccine adjuvants as potential cancer immunotherapeutics.

    PubMed

    Temizoz, Burcu; Kuroda, Etsushi; Ishii, Ken J

    2016-07-01

    Accumulated evidence obtained from various clinical trials and animal studies suggested that cancer vaccines need better adjuvants than those that are currently licensed, which include the most commonly used alum and incomplete Freund's adjuvant, because of either a lack of potent anti-tumor immunity or the induction of undesired immunity. Several clinical trials using immunostimulatory adjuvants, particularly agonistic as well as non-agonistic ligands for TLRs, C-type lectin receptors, retinoic acid-inducible gene I-like receptors and stimulator of interferon genes, have revealed their therapeutic potential not only as vaccine adjuvants but also as anti-tumor agents. Recently, combinations of such immunostimulatory or immunomodulatory adjuvants have shown superior efficacy over their singular use, suggesting that seeking optimal combinations of the currently available or well-characterized adjuvants may provide a better chance for the development of novel adjuvants for cancer immunotherapy. PMID:27006304

  15. Improving vaccine delivery using novel adjuvant systems.

    PubMed

    Pichichero, Michael E

    2008-01-01

    Adjuvants have been common additions to vaccines to help facilitate vaccine delivery. With advancements in vaccine technology, several adjuvants which activate immune specific responses have emerged. Available data show these adjuvants elicit important immune responses in both healthy and immunocompromised populations, as well as the elderly. Guidelines for the use and licensure of vaccine adjuvants remain under discussion. However, there is a greater understanding of the innate and adaptive immune response, and the realization of the need for immune specific adjuvants appears to be growing. This is a focused review of four adjuvants currently in clinical trial development: ASO4, ASO2A, CPG 7907, and GM-CSF. The vaccines including these adjuvants are highly relevant today, and are expected to reduce the disease burden of cervical cancer, hepatitis B and malaria. PMID:18398303

  16. Vaccine adjuvants as potential cancer immunotherapeutics

    PubMed Central

    Temizoz, Burcu; Kuroda, Etsushi

    2016-01-01

    Accumulated evidence obtained from various clinical trials and animal studies suggested that cancer vaccines need better adjuvants than those that are currently licensed, which include the most commonly used alum and incomplete Freund’s adjuvant, because of either a lack of potent anti-tumor immunity or the induction of undesired immunity. Several clinical trials using immunostimulatory adjuvants, particularly agonistic as well as non-agonistic ligands for TLRs, C-type lectin receptors, retinoic acid-inducible gene I-like receptors and stimulator of interferon genes, have revealed their therapeutic potential not only as vaccine adjuvants but also as anti-tumor agents. Recently, combinations of such immunostimulatory or immunomodulatory adjuvants have shown superior efficacy over their singular use, suggesting that seeking optimal combinations of the currently available or well-characterized adjuvants may provide a better chance for the development of novel adjuvants for cancer immunotherapy. PMID:27006304

  17. Chemotherapy in locally advanced head and neck squamous cell carcinoma.

    PubMed

    Gyawali, Bishal; Shimokata, Tomoya; Honda, Kazunori; Ando, Yuichi

    2016-03-01

    Chemotherapy, in combination with a local treatment, has a role in nearly all the settings of locally advanced head and neck squamous cell carcinoma (LAHNSCC) treatment: as definitive, adjuvant or induction therapy. However, despite many years of trials, controversies still exist regarding the best approach to using chemotherapy in the multi-modal treatment of LAHNSCC. Opinions are divided on sequential versus concurrent use of chemotherapy and radiotherapy for unresectable LAHNSCC. More debate exists on whether the addition of induction chemotherapy to concomitant chemoradiotherapy is clinically meaningful. After the approval of cetuximab in combination with radiotherapy for this disease, making treatment choices have become further complicated. Although new data from trials are arriving every year, the results have been inconclusive. In this review, we provide the readers with the latest information on various strategies of using chemotherapy and cetuximab that will help to make an evidence-based decision in the treatment of LAHNSCC, including the approach to larynx preservation. We conclude that with the available information, concurrent chemoradiotherapy should be preferred over induction chemotherapy, except in the setting of larynx preservation. Furthermore, given the paucity of positive data and severe financial toxicity associated with cetuximab, concurrent chemoradiotherapy should be the preferred choice over cetuximab-radiotherapy. Future trials in head and neck cancer should be properly planned to address these controversies and provide clear solutions. PMID:26924194

  18. High Id1 expression, a generally negative prognostic factor, paradoxically predicts a favorable prognosis for adjuvant paclitaxel plus cisplatin therapy in surgically treated lung cancer patients

    PubMed Central

    Cheng, Yu-Jen; Lee, Yi-Chen; Chiu, Wen-Chin; Tsai, Jen-Wei; Su, Yu-Han; Hung, Amos C.; Chang, Po-Chih; Huang, Chih-Jen; Chai, Chee-Yin; Yuan, Shyng-Shiou F.

    2014-01-01

    Adjuvant chemotherapy is commonly given to surgically treated non-small-cell lung cancer (NSCLC) patients. However, the prerequisite for chemotherapy needs to be scrutinized in order to maximize the benefits to patients. In this study, we observed that NSCLC cells with high Id1 protein expression were vulnerable to the treatment of paclitaxel and cisplatin. In addition, paclitaxel and cisplatin caused Id1 protein degradation through ubiquitination. In the nude mice xenograft model, the tumor growth was reduced to a large degree in the Id1-overexpressing group upon treatment with paclitaxel and cisplatin. Furthermore, immunohistochemical staining for Id1 followed by Kaplan-Meier survival analysis showed that surgically treated NSCLC patients with high Id1 expression in primary tumor tissues had better disease-free and overall survivals after adjuvant paclitaxel and cisplatin chemotherapy. In summary, our current data suggest that Id1, a generally negative prognostic factor, predicts a favorable prognosis in the case of surgically treated NSCLC patients receiving the definitive adjuvant chemotherapy. The distinct role of Id1 reported in this study may arise from the phenomenon of Id1 dependence of NSCLC cells for survival, which renders the cancer cells additionally susceptive to the adjuvant chemotherapy with paclitaxel and cisplatin. PMID:25344919

  19. Chemotherapy Altered Brain Functional Connectivity in Women with Breast Cancer: A Pilot Study

    PubMed Central

    Dumas, Julie A.; Makarewicz, Jenna; Schaubhut, Geoffrey J.; Devins, Robert; Albert, Kimberly; Dittus, Kim; Newhouse, Paul A.

    2013-01-01

    Adjuvant chemotherapy is associated with improvements in long-term cancer survival. However, reports of cognitive impairment following treatment emphasize the importance of understanding the long-term effects of chemotherapy on brain functioning. Cognitive deficits found in chemotherapy patients suggest a change in brain functioning that affects specific cognitive domains such as attentional processing and executive functioning. This study examined the processes potentially underlying these changes in cognition by examining brain functional connectivity pre- and post-chemotherapy in women with breast cancer. Functional connectivity examines the temporal correlation between spatially remote brain regions in an effort to understand how brain networks support specific cognitive functions. Nine women diagnosed with breast cancer completed a functional magnetic resonance imaging (fMRI) session before chemotherapy, one month after, and one year after the completion of chemotherapy. Seed-based functional connectivity analyses were completed using seeds in the intraparietal sulcus (IPS) to examine connectivity in the dorsal anterior attention network and in the posterior cingulate cortex (PCC) to examine connectivity in the default mode network. Results showed decreased functional connectivity one month after chemotherapy that partially returned to baseline at one year in the dorsal attention network. Decreased connectivity was seen in the default mode network at one month and one year following chemotherapy. In addition, increased subjective memory complaints were noted at one month and one year post-chemotherapy. These findings suggest a detrimental effect of chemotherapy on brain functional connectivity that is potentially related to subjective cognitive assessment. PMID:23852814

  20. Chemotherapy-Related Neurotoxicity.

    PubMed

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

    2016-09-01

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

  1. Biosafe Nanoscale Pharmaceutical Adjuvant Materials

    PubMed Central

    Jin, Shubin; Li, Shengliang; Wang, Chongxi; Liu, Juan; Yang, Xiaolong; Wang, Paul C.; Zhang, Xin; Liang, Xing-Jie

    2014-01-01

    Thanks to developments in the field of nanotechnology over the past decades, more and more biosafe nanoscale materials have become available for use as pharmaceutical adjuvants in medical research. Nanomaterials possess unique properties which could be employed to develop drug carriers with longer circulation time, higher loading capacity, better stability in physiological conditions, controlled drug release, and targeted drug delivery. In this review article, we will review recent progress in the application of representative organic, inorganic and hybrid biosafe nanoscale materials in pharmaceutical research, especially focusing on nanomaterial-based novel drug delivery systems. In addition, we briefly discuss the advantages and notable functions that make these nanomaterials suitable for the design of new medicines; the biosafety of each material discussed in this article is also highlighted to provide a comprehensive understanding of their adjuvant attributes. PMID:25429253

  2. Adjuvant therapy for endometrial cancer

    PubMed Central

    DeLeon, Maria C.; Ammakkanavar, Natraj R.

    2014-01-01

    Endometrial cancer is a common gynecologic malignancy typically diagnosed at early stage and cured with surgery alone. Adjuvant therapy is tailored according to the risk of recurrence, estimated based on the International Federation of Gynecology and Obstetrics (FIGO) stage and other histological factors. The objective of this manuscript is to review the evidence guiding adjuvant therapy for early stage and locally advanced uterine cancer. For patients with early stage disease, minimizing toxicity, while preserving outstanding cure rates remains the major goal. For patients with locally advanced endometrial cancer optimal combined regimens are being defined. Risk stratification based on molecular traits is under development and may aid refine the current risk prediction model and permit personalized approaches for women with endometrial cancer. PMID:24761218

  3. Polysaccharides: Candidates of promising vaccine adjuvants.

    PubMed

    Li, Pingli; Wang, Fengshan

    2015-04-01

    Aluminium-based adjuvants remain the only adjuvants approved for human use in the USA for over 80 years because of alum's simplicity, tolerability, safety and cost-efficiency. Recent development of vaccines, especially the increasing applications of recombinant subunit and synthetic vaccines, makes aluminium adjuvants cannot stimulate enough immunity to the antigens, since aluminium adjuvants can only induce Th2 type immune responses. So, novel adjuvants are urgent to make up the disadvantages of aluminium adjuvants. However, some major hurdles need to be overcome, not only the scientific knowledge of adjuvants but also unacceptable side-effects and toxicity. A number of carbohydrate-based polysaccharides from plant, bacterial, yeast and synthetic sources can act as pathogen-associated molecular patterns (PAMPs) and recognize pattern recognition receptors (PRRs) on immune cells, followed by triggering innate immunity and regulating adaptive immunity. What is more, polysaccharides are safe and biodegradable without tissue deposits as observed in aluminium adjuvants. Therefore, polysaccharide-based compounds and formulations are potential vaccine adjuvant candidates. Here, we mainly review polysaccharide-based adjuvants investigated in recent years. PMID:25994059

  4. Role of Adjuvant Chemoradiation Therapy in Adenocarcinomas of the Ampulla of Vater

    SciTech Connect

    Krishnan, Sunil Rana, Vishal; Evans, Douglas B.; Varadhachary, Gauri; Das, Prajnan; Bhatia, Sumita; Delclos, Marc E.; Janjan, Nora A.; Wolff, Robert A.; Crane, Christopher H.; Pisters, Peter W.

    2008-03-01

    Purpose: The role of adjuvant chemoradiation therapy (CRT) in the treatment of ampullary cancers remains undefined. We retrospectively compared treatment outcomes in patients treated with pancreaticoduodenectomy alone versus those who received additional adjuvant CRT. Methods and Materials: Between May 1990 and January 2006, 54 of 96 patients with ampullary adenocarcinoma who underwent potentially curative pancreaticoduodenectomy also received adjuvant CRT. The median preoperative radiation dose was 45 Gy (range, 30-50.4 Gy) and median postoperative dose was 50.4 Gy (range, 45-55.8 Gy). Concurrent chemotherapy included primarily 5-fluorouracil (52%) and capecitabine (43%). Median follow-up was 31 months. Univariate and multivariate statistical methodologies were used to determine significant prognostic factors for local control (LC), distant control (DC), and overall survival (OS). Results: Actuarial 5-year LC, DC, and OS were 77%, 69%, and 64%, respectively. On univariate analysis, age, gender, race/ethnicity, tumor grade, use of adjuvant treatment, and sequencing of adjuvant therapy were not significantly associated with LC, DC, or OS. However, on univariate analysis, T3/T4 tumor stage was prognostic for poorer LC and OS (p = 0.02 and p < 0.001, respectively); node-positive disease was prognostic for poorer LC (p = 0.03). On multivariate analysis, T3/T4 tumor stage was independently prognostic for decreased OS (p = 0.002). Among these patients (n = 34), those who received adjuvant CRT had a trend toward improved OS (median, 35.2 vs. 16.5 months; p = 0.06). Conclusions: Ampullary cancers have a distinctly better treatment outcome than pancreatic adenocarcinomas. Higher primary tumor stage (T3/T4), an independent adverse risk factor for poorer treatment outcomes, may warrant the addition of adjuvant CRT to pancreaticoduodenectomy.

  5. Arterial, portal, or systemic chemotherapy for patients with hepatic metastasis of colorectal carcinoma.

    PubMed

    Kemeny, N; Fata, F

    1999-01-01

    Hepatic metastases from colorectal carcinoma are common and may be resected for cure. The response of liver metastases to systemic chemotherapy is low. In contrast, hepatic arterial chemotherapy produces higher response rates than systemic chemotherapy, but randomized trials have not definitely proved a survival advantage because they allowed cross over. Most adjuvant portal vein chemotherapy studies have shown a survival advantage over the control group, but it is not clear whether this benefit is from the portal vein therapy or from immediate postoperative chemotherapy, since there is rarely a reduction in liver metastases. We describe the results of systemic, hepatic artery infusion, and portal therapy for patients with liver metastases of colorectal carcinoma. PMID:10436236

  6. Risk of Marrow Neoplasms After Adjuvant Breast Cancer Therapy: The National Comprehensive Cancer Network Experience

    PubMed Central

    Wolff, Antonio C.; Blackford, Amanda L.; Visvanathan, Kala; Rugo, Hope S.; Moy, Beverly; Goldstein, Lori J.; Stockerl-Goldstein, Keith; Neumayer, Leigh; Langbaum, Terry S.; Theriault, Richard L.; Hughes, Melissa E.; Weeks, Jane C.; Karp, Judith E.

    2015-01-01

    Purpose Outcomes for early-stage breast cancer have improved. First-generation adjuvant chemotherapy trials reported a 0.27% 8-year cumulative incidence of myelodysplastic syndrome/acute myelogenous leukemia. Incomplete ascertainment and follow-up may have underestimated subsequent risk of treatment-associated marrow neoplasm (MN). Patients and Methods We examined the MN frequency in 20,063 patients with stage I to III breast cancer treated at US academic centers between 1998 and 2007. Time-to-event analyses were censored at first date of new cancer event, last contact date, or death and considered competing risks. Cumulative incidence, hazard ratios (HRs), and comparisons with Surveillance, Epidemiology, and End Results estimates were obtained. Marrow cytogenetics data were reviewed. Results Fifty patients developed MN (myeloid, n = 42; lymphoid, n = 8) after breast cancer (median follow-up, 5.1 years). Patients who developed MN had similar breast cancer stage distribution, race, and chemotherapy exposure but were older compared with patients who did not develop MN (median age, 59.1 v 53.9 years, respectively; P = .03). Two thirds of patients had complex MN cytogenetics. Risk of MN was significantly increased after surgery plus chemotherapy (HR, 6.8; 95% CI, 1.3 to 36.1) or after all modalities (surgery, chemotherapy, and radiation; HR, 7.6; 95% CI, 1.6 to 35.8), compared with no treatment with chemotherapy. MN rates per 1,000 person-years were 0.16 (surgery), 0.43 (plus radiation), 0.46 (plus chemotherapy), and 0.54 (all three modalities). Cumulative incidence of MN doubled between years 5 and 10 (0.24% to 0.48%); 9% of patients were alive at 10 years. Conclusion In this large early-stage breast cancer cohort, MN risk after radiation and/or adjuvant chemotherapy was low but higher than previously described. Risk continued to increase beyond 5 years. Individual risk of MN must be balanced against the absolute survival benefit of adjuvant chemotherapy. PMID

  7. Adjuvant progestagens for endometrial cancer

    PubMed Central

    Martin-Hirsch, Pierre PL; Bryant, Andrew; Keep, Sarah L; Kitchener, Henry C; Lilford, Richard

    2014-01-01

    Background Endometrial cancer is the most common genital tract carcinoma among women in developed countries, with most women presenting with stage 1 disease. Adjuvant progestagen therapy has been advocated following primary surgery to reduce the risk of recurrence of disease. Objectives To evaluate the effectiveness and safety of adjuvant progestagen therapy for the treatment of endometrial cancer. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Specilaised Register, Cochrane Central Register of Controlled Trials (CENTRAL) Issue 2, 2009. MEDLINE and EMBASE up to April 2009. Selection criteria Randomised controlled trials (RCTs) of progestagen therapy in women who have had surgery for endometrial cancer. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Risk ratios (RRs) comparing survival in women who did and did not receive progestagen were pooled in random effects meta-analyses.. Main results Seven trials assessing 4556 women were identified. Three trials included women with stage one disease only, whereas four included women with more advanced disease. Meta-analysis of four trials showed that there was no significant difference in the risk of death at five years between adjuvant progestagen therapy and no further treatment (RR = 1.00, 95% CI 0.85 to 1.18). This conclusion is also robust to single trial analyses at 4 and 7 years and in one trial across all points in time using a hazard ratio (HR). There was also no significant difference between progestagen therapy and control in terms of the risk of death from endometrial cancer, cardiovascular disease and intercurrent disease. Relapse of disease appeared to be reduced by progestagen therapy in one trial (HR = 0.71, 95% CI 0.52 to 0.97 and 5 year RR = 0.74, 95% CI 0.58 to 0.96), but there was no evidence of a difference in disease recurrence in another trial at 7 years (RR = 1.34, 95% CI 0.79 to 2.27). Authors’ conclusions There

  8. The role of neoadjuvant and adjuvant treatment for adenocarcinoma of the upper gastrointestinal tract

    PubMed Central

    2011-01-01

    Both locally advanced adenocarcinoma of the stomach and gastro-esophageal junction are associated with poor prognosis due to the lack of effective treatment. Recently multimodal treatment consisting of neoadjuvant chemotherapy in combination with radiotherapy is reported to improve survival when compared to surgery alone. Neoadjuvant therapy in these locally advanced tumors allows for early tumor responses and the extent of tumor regression that can be achieved is considered a significant prognostic factor. This, in turn, increases the resectability of these tumors. Also due to the high frequency of lymph node metastasis, patients with locally advanced adenocarcinoma should undergo a D2 lymphadenectomy. Postoperative chemoradiation and perioperative chemotherapy have been studied in gastric adenocarcinomas and showed a survival benefit. However, the surgical techniques used in these trials are no longer considered to be standard by today's surgical practice. In addition, there are no standard recommendations for adjuvant chemotherapy or chemoradiation after R0 resection and adequate lymph node dissection. PMID:21810561

  9. Thermal potentiation of chemotherapy by magnetic nanoparticles

    PubMed Central

    Torres-Lugo, Madeline; Rinaldi, Carlos

    2014-01-01

    Clinical studies have demonstrated the effectiveness of hyperthermia as an adjuvant for chemotherapy and radiotherapy. However, significant clinical challenges have been encountered, such as a broader spectrum of toxicity, lack of patient tolerance, temperature control and significant invasiveness. Hyperthermia induced by magnetic nanoparticles in high-frequency oscillating magnetic fields, commonly termed magnetic fluid hyperthermia, is a promising form of heat delivery in which thermal energy is supplied at the nanoscale to the tumor. This review discusses the mechanisms of heat dissipation of iron oxide-based magnetic nanoparticles, current methods and challenges to deliver heat in the clinic, and the current work related to the use of magnetic nanoparticles for the thermal-chemopotentiation of therapeutic drugs. PMID:24074390

  10. Chemotherapy of prostate cancer: present and future.

    PubMed

    Trump, Donald; Lau, Yiu-Keung

    2003-06-01

    The role of chemotherapy in prostate cancer continues to evolve. In men with symptomatic androgen-independent prostate cancer, significant reduction in pain and analgesic requirements are achievable with mitoxantrone and glucocorticoid combinations compared with glucocorticoids alone. However, survival rates are not improved. Taxane-based combinations with estramustine phosphate or other new agents show promise. Prostate-specific antigen response rates with these combinations appear to be 1.5 to 2 times more frequent than with mitoxantrone-based combinations. Randomized trials of taxane versus mitoxantrone-based therapies are underway. New agents and applications of current agents in adjuvant settings should be explored if survival in men with prostate cancer is to be improved. PMID:12756087

  11. Adjuvant systemic therapy in older women with breast cancer

    PubMed Central

    Leone, Julieta; Leone, Bernardo Amadeo; Leone, José Pablo

    2016-01-01

    Breast cancer in the elderly is an increasing clinical problem. In addition, ~60% of deaths from breast cancer occur in women aged 65 years and older. Despite this, older women with breast cancer have been underrepresented in clinical trials, and this has led to less than optimal evidence to guide their therapy. The management of elderly women with early breast cancer is a complex process that requires careful evaluation of life expectancy, comorbidities, patient values, and risks and benefits of available treatment options. This review will focus on current adjuvant systemic therapy options for older women with breast cancer, discuss the principles in the decision-making process, and define the role of endocrine therapy, chemotherapy, and targeted agents. PMID:27524919

  12. Surgeons’ Volume of Colorectal Cancer Procedures and Collaborative Decision-making about Adjuvant Therapies

    PubMed Central

    Rogers, Selwyn O.; Ayanian, John Z.; Ko, Clifford Y.; Kahn, Katherine L.; Zaslavsky, Alan M.; Sandler, Robert S.; Keating, Nancy L.

    2011-01-01

    Background Few studies have assessed associations of surgeons’ practice volume with processes of care that lead to better outcomes. Objective We surveyed surgeons treating colorectal cancer to determine whether high-volume surgeons were more likely to collaborate with other physicians in decisions about adjuvant therapies. Subjects and methods Surgeons caring for patients with colorectal cancer in multiple regions and health-care organizations were surveyed to assess their volume of colorectal cancer resections and participation in decisions about adjuvant chemotherapy and radiation therapy. We used logistic regression to assess physician and practice characteristics associated with surgical volume and the relation of surgical volume and these other characteristics to collaborative decision-making regarding adjuvant therapies. Results Of 635 responding surgeons, those who identified themselves as surgical oncologists or colorectal surgeons were more likely than others to report high volume of colorectal cancer resections (p<.001), as were those who practiced at a comprehensive cancer center (P=.06) and attended tumor board meetings weekly (vs. quarterly or less, P=.09). Most surgeons reported a collaborative role in decisions about chemotherapy and radiation therapy. However, in adjusted analyses, higher-volume surgeons more often reported a collaborative role with other physicians in decisions about chemotherapy (P<0.001) and radiation therapy (P<0.001). Conclusions Higher-volume surgeons are more likely to report collaborating with other physicians in decisions about adjuvant therapies for patients following colorectal cancer surgery. This collaborative decision-making of higher-volume surgeons may contribute to outcome differences by surgeon volume. PMID:19855265

  13. Adjuvant photodynamic therapy (PDT) of the superficial bladder cancer

    NASA Astrophysics Data System (ADS)

    Sokolov, V. V.; Russakov, I. G.; Teplov, A. A.; Filonenko, E. V.; Ul'yanov, R. V.; Bystrov, A. A.

    2005-08-01

    Superficial transitional cell carcinoma represents 50 to 80% of newly diagnosed bladder cancer in various countries. Transurethral resection of the urinary bladder is the standard procedure for biopsy and treatment superficial bladder cancer. However recurrence tumors after transurethral resection alone is high enough (50-90%). Intravesical chemotherapy for prophylaxis after complete transurethral resection is reducing recurrence rate about 1 5%. Adjuvant intravesical Bacillus of Calmette and Guerin (BCG) is reducing recurrence rate about 30%, but frequency side effects of this therapy is very high. Purpose of this study is appreciate efficacy adjuvant PDT with photosensitizer Photogeme (Russia) of superficial bladder cancer for prophylaxis after complete transurethral resection. The follow up was from 3 to 63 months (27 months, on average). Sixty-five patients (75.6%) showed no recurrence. For the follow up period, the recurrence was revealed in 21 (24.4%) patient, in two of them it was progressing (one case of invasive growth and one case of remote metastases). Four cases of recurrence were revealed 4 months after the surgery. In other cases, the recurrence was diagnosed from 9 to 18 months.

  14. [Standards and new developments in the chemotherapy of glioblastomas].

    PubMed

    Weller, M

    2005-10-01

    For 25 years involved-field radiotherapy has remained the mainstay of postoperative treatment for glioblastoma. In contrast, the role of adjuvant chemotherapy in addition to radiotherapy has remained controversial. A recent randomized multinational phase III trial (EORTC 26 981/22 981/NCIC CE.3) assessing concomitant and adjuvant chemotherapy with the alkylating agent, temozolomide, in addition to radiotherapy in newly diagnosed glioblastoma defines an increase in median survival from 12.1 months with radiotherapy alone to 14.6 months with radiochemotherapy and an increase in the 2-year survival rate from 10 to 26 %. Subgroup analysis revealed that the gain in survival in the experimental arm was largely achieved in patients with glioblastomas which exhibited a methylation of the promoter region of the O (6)-methylguanine DNA methyltransferase (MGMT) gene and thus did not express MGMT. MGMT is a DNA repair enzyme which repairs DNA lesions induced by chemotherapy with alkylating agents. The cellular MGMT stores are consumed during DNA repair, suggesting that temozolomide itself may deplete MGMT and thus overcome its own most important pathway of resistance. EORTC 26 981/22 981/NCIC CE.3 thus defines a milestone in the treatment of glioblastoma and will provide a platform for further efforts at improving the outcome for patients suffering from this still invariably fatal neoplasm. PMID:16208603

  15. Selection of chemotherapy for non-small cell lung cancer is facilitated by new therapeutic strategies

    PubMed Central

    Wang, Zhehai

    2014-01-01

    Nowadays, advanced non-small cell lung cancer is still an incurable disease. Recent researches have led to considerable progress in the treatment of non-small cell lung cancer. This article reviews the main studies on chemotherapy on non-small cell lung cancer and discusses the new therapeutic strategies available to date. Stable disease (SD) is necessary in chemotherapy for tumor. The proportion of population with responders or SD basically maintained similar regardless of regimens. The overall survival after chemotherapy for patients with SD was lower than patients with responders, and higher than patients with progressive disease. Greater benefits could be achieved in patients with effective induction chemotherapy using chemotherapeutic agents for maintenance therapy, whereas the benefits were relatively small for patients with SD. It has been found that epidermal growth factor receptor (EGFR) mutation status had certain correlation with the efficacy of chemotherapy. First-line chemotherapy has shown advantages in effective rate and progression free survival on EGFR mutant. EGFR mutation produced significant effects on the efficacy of postoperative adjuvant chemotherapy. Patients with EGFR mutation had a higher effective rate than wild-type EGFR patients, and patients with responders had a greater benefit in progression free survival from maintenance therapy. However, it is still necessary to carry out more careful and deeper studies and analyses on traditional cytotoxic chemotherapy, to further optimize cytotoxic chemotherapy and to use molecular targeted agents with different mechanisms. PMID:25550891

  16. Chemotherapy (For Parents)

    MedlinePlus

    ... sample before beginning chemotherapy to evaluate kidney function. Giving your child plenty of fluids to drink will ... eating, after using the bathroom, and after touching animals. They shouldn't share cups or utensils with ...

  17. Adjuvant chemo- and hormonal therapy in locally advanced breast cancer: a randomized clinical study

    SciTech Connect

    Schaake-Koning, C.; van der Linden, E.H.; Hart, G.; Engelsman, E.

    1985-10-01

    Between 1977 and 1980, 118 breast cancer patients with locally advanced disease, T3B-4, any N, M0 or T1-3, tumor positive axillary apex biopsy, were randomized to one of three arms: I: radiotherapy (RT) to the breast and adjacent lymph node areas; II: RT followed by 12 cycles of cyclophosphamide, methotrexate, 5 fluorouracil (CMF) and tamoxifen during the chemotherapy period; III: 2 cycles of adriamycin and vincristine (AV), alternated with 2 cycles of CMF, then RT, followed by another 4 cycles of AV, alternated with 4 CMF; tamoxifen during the entire treatment period. The median follow-up period was 5 1/2 years. The adjuvant chemo- and hormonal therapy did not improve the overall survival; the 5-year survival was 37% for all three treatment arms. There was no statistically significant difference in RFS between the three modalities, nor when arm I was compared to arm II and III together. LR was not statistically different over the three treatment arms. In 18 of the 24 patients with LR, distant metastases appeared within a few months from the local recurrence. The menopausal status did not influence the treatment results. Dose reduction in more than 4 cycles of chemotherapy was accompanied by better results. In conclusion: adjuvant chemo- and hormonal therapy did not improve RFS and overall survival. These findings do not support the routine use of adjuvant chemo- and endocrine therapy for inoperable breast cancer.

  18. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Methodology, Drugs and Bidirectional Chemotherapy.

    PubMed

    Valle, S J; Alzahrani, N A; Liauw, W; Sugarbaker, P H; Bhatt, A; Morris, D L

    2016-06-01

    Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) combined have been recognized as standard of care for treatment of a subset of patients with peritoneal carcinomatosis (PC). The aim of CRS is to eliminate all macroscopic disease through a series of visceral resections followed by targeting any residual microscopic disease with intraperitoneal chemotherapy, exposing the peritoneal surfaces to a high concentration of chemotherapy with a lower systemic toxicity. Different regimes of intraperitoneal chemotherapy include HIPEC, early postoperative intraperitoneal chemotherapy (EPIC) and bidirectional chemotherapy. The efficacy and modality of treatment with intraperitoneal chemotherapy is dependent on multiple factors including the chosen cytotoxic agent and its pharmacokinetics and pharmacodynamics. There is no standardized methodology for intraperitoneal chemotherapy administration. This review will discuss the pharmacological principles of the various intraperitoneal chemotherapy techniques. PMID:27065705

  19. Quality of life during chemotherapy in lung cancer patients: results across different treatment lines

    PubMed Central

    Wintner, L M; Giesinger, J M; Zabernigg, A; Sztankay, M; Meraner, V; Pall, G; Hilbe, W; Holzner, B

    2013-01-01

    Background: Most lung cancer patients are diagnosed at an advanced disease stage and predominantly receive palliative treatment, which increasingly consists of several chemotherapy lines. We report on patients' quality of life (QOL) to gain knowledge on QOL during and across multiple lines of chemotherapy. This includes patients with (neo)adjuvant therapy up to 3rd or above line palliative chemotherapy. Methods: Lung cancer patients receiving outpatient chemotherapy at the Kufstein County Hospital completed an electronic version of the EORTC QLQ-C30. Linear mixed models were used for statistical analysis. Results: One hundred and eighty seven patients were included in the study. Surprisingly, irrespective of the chemotherapy line patients reported stable QOL scores during treatment. None of the calculated monthly change rates attained clinical significance, referring to established guidelines that classify a small clinical meaningful change as 5 to 10 points. According to treatment line, 3rd or above line palliative chemotherapy was associated with the worst QOL scores, whereas patients undergoing (neo)adjuvant or 1st line palliative chemotherapy reported fairly comparable QOL. Conclusion: The essential finding of our study is that all QOL aspects of the EORTC QLQ-C30 questionnaire remained unchanged during each chemotherapy line in an unselected population of lung cancer patients. Between treatment lines pronounced differences were found, indicating that later palliative chemotherapy lines are associated with higher QOL impairments. These changes in QOL may not primarily be related to the treatment, but rather refer to impairments due to disease progression and may be partly due to a consequence of the prior therapies. PMID:24091620

  20. Chemotherapy for colorectal cancer in the elderly

    PubMed Central

    Kim, Jung Han

    2015-01-01

    Colorectal cancer (CRC) is one of the leading causes of cancer-related death in the elderly. However, elderly patients with CRC tend to be under-presented in clinical trials and undertreated in clinical practice. Advanced age alone should not be the only criteria to preclude effective therapy in elderly patients with CRC. The best guide about optimal cancer treatment can be provided by comprehensive geriatric assessment. Elderly patients with stage III colon cancer can enjoy the same benefit from adjuvant chemotherapy with 5-fluorouracil/leucovorin or capecitabine as younger patients, without a substantial increase in toxicity. With conflicting results of retrospective studies and a lack of data available from randomized studies, combined modality treatment should be used with great caution in elderly patients with locally advanced rectal cancer. Combination chemotherapy can be considered for older patients with metastatic CRC. For elderly patients who are frail or vulnerable, however, monotherapy or a stop-and-go strategy may be desirable. The use of targeted therapies in older patients with metastatic CRC appears to be promising in view of their better efficacy and toxicity. Treatment should be individualized based on the nature of the disease, the physiologic or functional status, and the patient’s preference. PMID:25954089

  1. Adjuvant radiotherapy following radical hysterectomy for patients with stage IB and IIA cervical cancer

    SciTech Connect

    Soisson, A.P.; Soper, J.T.; Clarke-Pearson, D.L.; Berchuck, A.; Montana, G.; Creasman, W.T. )

    1990-06-01

    From 1971 through 1984, 320 women underwent radical hysterectomy as primary therapy of stage IB and IIA cervical cancer. Two hundred forty-eight patients (78%) were treated with surgery alone and 72 patients (22%) received adjuvant postoperative external-beam radiotherapy. Presence of lymph node metastasis, large lesion (greater than 4 cm in diameter), histologic grade, race (noncaucasian), and age (greater than 40 years) were significant poor prognostic factors for the entire group of patients. Patients treated with surgery alone had a better disease-free survival than those who received combination therapy (P less than 0.001). However, patients receiving adjuvant radiation therapy had a higher incidence of lymphatic metastases, tumor involvement of the surgical margin, and large cervical lesions. Adjuvant pelvic radiation therapy did not improve the survival of patients with unilateral nodal metastases or those who had a large cervical lesion with free surgical margins and the absence of nodal involvement. Radiation therapy appears to reduce the incidence of pelvic recurrences. Unfortunately, 84% of patients who developed recurrent tumor after combination therapy had a component of distant failure. The incidence of severe gastrointestinal or genitourinary tract complications was not different in the two treatment groups. However, the incidence of lymphedema was increased in patients who received adjuvant radiation therapy. Although adjuvant radiation therapy appears to be tolerated without a significant increase in serious complications, the extent to which it may improve local control rates and survival in high-risk patients appears to be limited. In view of the high incidence of distant metastases in high-risk patients, consideration should be given to adjuvant systemic chemotherapy in addition to radiation therapy.

  2. Primary Ewing's sarcoma of the squamous part of temporal bone in a young girl treated with adjuvant volumetric arc therapy.

    PubMed

    Nandi, Moujhuri; Bhattacharya, Jibak; Goswami, Suchanda; Goswami, Chanchal

    2015-01-01

    Ewing's sarcoma (ES)/peripheral primitive neuroectodermal tumors usually arise in the long bones of children and young adults. Primary ES of the cranium is unusual. Treatment involves multi-modality therapy incorporating surgery, radiotherapy and chemotherapy; outcomes are similar to those arising from long bones. We report a case of Primary ES of the squamous part of temporal bone with intracranial extension in a 9-year-old girl who was treated with surgery, chemotherapy followed by adjuvant radiotherapy by volumetric arc therapy. Post 1-year of treatment the girl is performing well in her classes. PMID:26881573

  3. Adjuvants: Classification, Modus Operandi, and Licensing

    PubMed Central

    Apostólico, Juliana de Souza

    2016-01-01

    Vaccination is one of the most efficient strategies for the prevention of infectious diseases. Although safer, subunit vaccines are poorly immunogenic and for this reason the use of adjuvants is strongly recommended. Since their discovery in the beginning of the 20th century, adjuvants have been used to improve immune responses that ultimately lead to protection against disease. The choice of the adjuvant is of utmost importance as it can stimulate protective immunity. Their mechanisms of action have now been revealed. Our increasing understanding of the immune system, and of correlates of protection, is helping in the development of new vaccine formulations for global infections. Nevertheless, few adjuvants are licensed for human vaccines and several formulations are now being evaluated in clinical trials. In this review, we briefly describe the most well known adjuvants used in experimental and clinical settings based on their main mechanisms of action and also highlight the requirements for licensing new vaccine formulations. PMID:27274998

  4. Role of Axillary Clearance After a Tumor-Positive Sentinel Node in the Administration of Adjuvant Therapy in Early Breast Cancer

    PubMed Central

    Straver, Marieke E.; Meijnen, Philip; van Tienhoven, Geertjan; van de Velde, Cornelis J.H.; Mansel, Robert E.; Bogaerts, Jan; Demonty, Gaston; Duez, Nicole; Cataliotti, Luigi; Klinkenbijl, Jean; Westenberg, Helen A.; van der Mijle, Huub; Hurkmans, Coen; Rutgers, Emiel J.T.

    2010-01-01

    Purpose The After Mapping of the Axilla: Radiotherapy or Surgery? (AMAROS) phase III study compares axillary lymph node dissection (ALND) and axillary radiation therapy (ART) in early breast cancer patients with tumor-positive sentinel nodes. In the ART arm, the extent of nodal involvement remains unknown, which could have implications on the administration of adjuvant therapy. In this preliminary analysis, we studied the influence of random assignment to ALND or ART on the choice for adjuvant treatment. Patients and Methods In the first 2,000 patients enrolled in the AMAROS trial, we analyzed the administration of adjuvant systemic therapy. Multivariate analysis was used to assess variables affecting the administration of adjuvant chemotherapy. Adjuvant therapy was applied according to institutional guidelines. Results Of 2,000 patients, 566 patients had a positive sentinel node and were treated per random assignment. There was no significant difference in the administration of adjuvant systemic therapy. In the ALND and ART arms, 58% (175 of 300) and 61% (162 of 266) of the patients, respectively, received chemotherapy. Endocrine therapy was administered in 78% (235 of 300) of the patients in the ALND arm and in 76% (203 of 266) of the patients in the ART arm. Treatment arm was not a significant factor in the decision, and no interactions between treatment arm and other factors were observed. Multivariate analysis showed that age, tumor grade, multifocality, and size of the sentinel node metastasis significantly affected the administration of chemotherapy. Within the ALND arm, the extent of nodal involvement remained not significant in a sensitivity multivariate analysis. Conclusion Absence of knowledge regarding the extent of nodal involvement in the ART arm appears to have no major impact on the administration of adjuvant therapy. PMID:20038733

  5. Identification of Novel FAM134B (JK1) Mutations in Oesophageal Squamous Cell Carcinoma

    PubMed Central

    Haque, Md. Hakimul; Gopalan, Vinod; Chan, Kwok-wah; Shiddiky, Muhammad J. A.; Smith, Robert Anthony; Lam, Alfred King-yin

    2016-01-01

    Mutation of FAM134B (Family with Sequence Similarity 134, Member B) leading to loss of function of its encoded Golgi protein and has been reported induce apoptosis in neurological disorders. FAM134B mutation is still unexplored in cancer. Herein, we studied the DNA copy number variation and novel mutation sites of FAM134B in a large cohort of freshly collected oesophageal squamous cell carcinoma (ESCC) tissue samples. In ESCC tissues, 37% (38/102) showed increased FAM134B DNA copies whereas 35% (36/102) showed loss of FAM134B copies relative to matched non-cancer tissues. Novel mutations were detected in exons 4, 5, 7, 9 as well as introns 2, 4-8 of FAM134B via HRM (High-Resolution Melt) and Sanger sequencing analysis. Overall, thirty-seven FAM134B mutations were noted in which most (31/37) mutations were homozygous. FAM134B mutations were detected in all the cases with metastatic ESCC in the lymph node tested and in 14% (8/57) of the primary ESCC. Genetic alteration of FAM134B is a frequent event in the progression of ESCCs. These findings imply that mutation might be the major driving source of FAM134B genetic modulation in ESCCs. PMID:27373372

  6. Identification of Novel FAM134B (JK1) Mutations in Oesophageal Squamous Cell Carcinoma.

    PubMed

    Haque, Md Hakimul; Gopalan, Vinod; Chan, Kwok-Wah; Shiddiky, Muhammad J A; Smith, Robert Anthony; Lam, Alfred King-Yin

    2016-01-01

    Mutation of FAM134B (Family with Sequence Similarity 134, Member B) leading to loss of function of its encoded Golgi protein and has been reported induce apoptosis in neurological disorders. FAM134B mutation is still unexplored in cancer. Herein, we studied the DNA copy number variation and novel mutation sites of FAM134B in a large cohort of freshly collected oesophageal squamous cell carcinoma (ESCC) tissue samples. In ESCC tissues, 37% (38/102) showed increased FAM134B DNA copies whereas 35% (36/102) showed loss of FAM134B copies relative to matched non-cancer tissues. Novel mutations were detected in exons 4, 5, 7, 9 as well as introns 2, 4-8 of FAM134B via HRM (High-Resolution Melt) and Sanger sequencing analysis. Overall, thirty-seven FAM134B mutations were noted in which most (31/37) mutations were homozygous. FAM134B mutations were detected in all the cases with metastatic ESCC in the lymph node tested and in 14% (8/57) of the primary ESCC. Genetic alteration of FAM134B is a frequent event in the progression of ESCCs. These findings imply that mutation might be the major driving source of FAM134B genetic modulation in ESCCs. PMID:27373372

  7. Adjuvant-induced Human Monocyte Secretome Profiles Reveal Adjuvant- and Age-specific Protein Signatures.

    PubMed

    Oh, Djin-Ye; Dowling, David J; Ahmed, Saima; Choi, Hyungwon; Brightman, Spencer; Bergelson, Ilana; Berger, Sebastian T; Sauld, John F; Pettengill, Matthew; Kho, Alvin T; Pollack, Henry J; Steen, Hanno; Levy, Ofer

    2016-06-01

    Adjuvants boost vaccine responses, enhancing protective immunity against infections that are most common among the very young. Many adjuvants activate innate immunity, some via Toll-Like Receptors (TLRs), whose activities varies with age. Accordingly, characterization of age-specific adjuvant-induced immune responses may inform rational adjuvant design targeting vulnerable populations. In this study, we employed proteomics to characterize the adjuvant-induced changes of secretomes from human newborn and adult monocytes in response to Alum, the most commonly used adjuvant in licensed vaccines; Monophosphoryl Lipid A (MPLA), a TLR4-activating adjuvant component of a licensed Human Papilloma Virus vaccine; and R848 an imidazoquinoline TLR7/8 agonist that is a candidate adjuvant for early life vaccines. Monocytes were incubated in vitro for 24 h with vehicle, Alum, MPLA, or R848 and supernatants collected for proteomic analysis employing liquid chromatography-mass spectrometry (LC-MS) (data available via ProteomeXchange, ID PXD003534). 1894 non-redundant proteins were identified, of which ∼30 - 40% were common to all treatment conditions and ∼5% were treatment-specific. Adjuvant-stimulated secretome profiles, as identified by cluster analyses of over-represented proteins, varied with age and adjuvant type. Adjuvants, especially Alum, activated multiple innate immune pathways as assessed by functional enrichment analyses. Release of lactoferrin, pentraxin 3, and matrix metalloproteinase-9 was confirmed in newborn and adult whole blood and blood monocytes stimulated with adjuvants alone or adjuvanted licensed vaccines with distinct clinical reactogenicity profiles. MPLA-induced adult monocyte secretome profiles correlated in silico with transcriptome profiles induced in adults immunized with the MPLA-adjuvanted RTS,S malaria vaccine (Mosquirix™). Overall, adjuvants such as Alum, MPLA and R848 give rise to distinct and age-specific monocyte secretome profiles

  8. Adjuvant treatment of node-positive breast cancer with adriamycin-cyclophosphamide with or without radiation therapy: interim results of an ongoing clinical trial.

    PubMed

    Jones, S E; Salmon, S E; Allen, H; Giordano, G F; Davis, S; Chase, E; Moon, T E; Heusinkveld, R S

    1982-01-01

    During 1974-1980, 138 women with node-positive stage II breast cancer were treated with either eight courses of adriamycin-cyclophosphamide (AC) chemotherapy (82 patients) or AC chemotherapy plus comprehensive regional radiotherapy (56 patients). The overall relapse-free survival of the treated patients was significantly superior (P less than 0.001) to a comparable group of women who underwent surgery alone. This effect of adjuvant therapy was clearly manifest in all groups of patients irrespective of nodal involvement or menopausal status. To date, relapse-free survival for patients receiving AC compared to AC plus radiotherapy is not different (P = 0.7). In summary, wer have demonstrated that a brief 6-month course of adjuvant chemotherapy with AC can significantly reduce the recurrence rate in women with stage II breast cancer. PMID:7036279

  9. Review of Adjuvant Radiochemotherapy for Resected Pancreatic Cancer and Results From Mayo Clinic for the 5th JUCTS Symposium

    SciTech Connect

    Miller, Robert C. Iott, Matthew J.; Corsini, Michele M.

    2009-10-01

    Purpose: To present an overview of Phase III trials in adjuvant therapy for pancreatic cancer and review outcomes at the Mayo Clinic after adjuvant radiochemotherapy (RT/CT) for resected pancreatic cancer. Methods and Materials: A literature review and a retrospective review of 472 patients who underwent an R0 resection for T1-3N0-1M0 invasive carcinoma of the pancreas from 1975 to 2005 at the Mayo Clinic, Rochester, MN. Patients with metastatic or unresectable disease at the time of surgery, positive surgical margins, or indolent tumors and those treated with intraoperative radiotherapy were excluded from the analysis. Median radiotherapy dose was 50.4Gy in 28 fractions, with 98% of patients receiving concurrent 5-fluorouracil- based chemotherapy. Results: Median follow-up was 2.7 years. Median overall survival (OS) was 1.8 years. Median OS after adjuvant RT/CT was 2.1 vs. 1.6 years for surgery alone (p = 0.001). The 2-y OS was 50% vs. 39%, and 5-y was 28% vs. 17% for patients receiving RT/CT vs. surgery alone. Univariate and multivariate analysis revealed that adverse prognostic factors were positive lymph nodes (risk ratio [RR] 1.3, p < 0.001) and high histologic grade (RR 1.2, p < 0.001). T3 tumor status was found significant on univariate analysis only (RR 1.1, p = 0.07). Conclusions: Results from recent clinical trials support the use of adjuvant chemotherapy in resected pancreatic cancer. The role of radiochemotherapy in adjuvant treatment of pancreatic cancer remains a topic of debate. Results from the Mayo Clinic suggest improved outcomes after the administration of adjuvant radiochemotherapy after a complete resection of invasive pancreatic malignancies.

  10. Uncaria tomentosa for Reducing Side Effects Caused by Chemotherapy in CRC Patients: Clinical Trial.

    PubMed

    Farias, I L G; Araújo, M C S; Farias, J G; Rossato, L V; Elsenbach, L I; Dalmora, S L; Flores, N M P; Durigon, M; Cruz, I B M; Morsch, V M; Schetinger, M R C

    2012-01-01

    To evaluate the effectiveness of Uncaria tomentosa in minimizing the side effects of chemotherapy and improving the antioxidant status of colorectal cancer (CRC) patients, a randomized clinical trial was conducted. Patients (43) undergoing adjuvant/palliative chemotherapy with 5-Fluorouracil/leucovorin + oxaliplatin (FOLFOX4) were split into two groups: the UT group received chemotherapy plus 300 mg of Uncaria tomentosa daily and the C group received only FOLFOX4 and served as a control. Blood samples were collected before each of the 6 cycles of chemotherapy, and hemograms, oxidative stress, enzymes antioxidants, immunologic parameters, and adverse events were analyzed. The use of 300 mg of Uncaria tomentosa daily during 6 cycles of FOLFOX4 did not change the analyzed parameters, and no toxic effects were observed. PMID:21869902

  11. Uncaria tomentosa for Reducing Side Effects Caused by Chemotherapy in CRC Patients: Clinical Trial

    PubMed Central

    Farias, I. L. G.; Araújo, M. C. S.; Farias, J. G.; Rossato, L. V.; Elsenbach, L. I.; Dalmora, S. L.; Flores, N. M. P.; Durigon, M.; Cruz, I. B. M.; Morsch, V. M.; Schetinger, M. R. C.

    2012-01-01

    To evaluate the effectiveness of Uncaria tomentosa in minimizing the side effects of chemotherapy and improving the antioxidant status of colorectal cancer (CRC) patients, a randomized clinical trial was conducted. Patients (43) undergoing adjuvant/palliative chemotherapy with 5-Fluorouracil/leucovorin + oxaliplatin (FOLFOX4) were split into two groups: the UT group received chemotherapy plus 300 mg of Uncaria tomentosa daily and the C group received only FOLFOX4 and served as a control. Blood samples were collected before each of the 6 cycles of chemotherapy, and hemograms, oxidative stress, enzymes antioxidants, immunologic parameters, and adverse events were analyzed. The use of 300 mg of Uncaria tomentosa daily during 6 cycles of FOLFOX4 did not change the analyzed parameters, and no toxic effects were observed. PMID:21869902

  12. Splenomegaly and Its Associations with Genetic Polymorphisms and Treatment Outcome in Colorectal Cancer Patients Treated with Adjuvant FOLFOX

    PubMed Central

    Kim, Mi-Jung; Han, Sae-Won; Lee, Dae-Won; Cha, Yongjun; Lee, Kyung-Hun; Kim, Tae-Yong; Oh, Do-Youn; Kim, Se Hyung; Im, Seock-Ah; Bang, Yung-Jue; Kim, Tae-You

    2016-01-01

    Purpose Splenomegaly is a clinical surrogate of oxaliplatin-induced sinusoidal obstruction syndrome (SOS). We investigated development of splenomegaly and its association with treatment outcome and genetic polymorphisms following adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) in colorectal cancer (CRC) patients. Materials and Methods Splenomegaly was determined by spleen volumetry using computed tomography images obtained before initiation of chemotherapy and after completion of adjuvant FOLFOX in CRC patients. Ten genetic polymorphisms in 4 SOS-related genes (VEGFA, MMP9, NOS3, and GSTP1) were analyzed using DNA from peripheral blood mononuclear cells. Results Of 124 patients included, increase in spleen size was observed in 109 (87.9%). Median change was 31% (range, –42% to 168%). Patients with splenomegaly had more severe thrombocytopenia compared to patients without splenomegaly during the chemotherapy period (p < 0.0001). The cumulative dose of oxaliplatin and the lowest platelet count during the chemotherapy period were clinical factors associated with splenomegaly. However, no significant associations were found between genetic polymorphisms and development of splenomegaly. Disease-free survival was similar regardless of the development of splenomegaly. Conclusion Splenomegaly was frequently observed in patients receiving adjuvant FOLFOX and resulted in more severe thrombocytopenia but did not influence treatment outcome. Examined genetic polymorphisms did not predict development of splenomegaly. PMID:26790967

  13. Integrating Chemotherapy in the Management of Cervical Cancer: A Critical Appraisal.

    PubMed

    Kumar, Lalit; Gupta, Sudeep

    2016-01-01

    The management of locally advanced cervix cancer has undergone a paradigm shift during the last decade. Concurrent chemoradiation (CCRT) (with cisplatin alone or in combination) is currently the standard treatment approach. CCRT results in a 5-year overall survival rate of 66% and a disease-free survival of 58%. About 30-40% of patients with locally advanced cervical cancer fail to achieve complete response to CCRT; alternative approaches are needed to improve the outcome for such patients. Weekly paclitaxel and carboplatin for 4-6 weeks as dose-dense chemotherapy prior to CCRT could be one such potential approach. The role of adjuvant chemotherapy after CCRT in patients with positive lymph nodes, larger tumor volume and stage III-IVA disease needs further exploration. Adjuvant chemotherapy is also being investigated for early-stage (stages IA2, IB1 or IIA) cervical cancer with presence of risk factors such as lymph node metastasis, lymphovascular space invasion and invasion depth of more than 10 mm, microscopic parametrial invasion, non-squamous histology and positive surgical margins. For patients with early-stage disease (IA2-IIA), short-course chemotherapy prior to surgery is associated with an improved outcome in many studies. Neo-adjuvant chemotherapy followed by fertility preservation surgery is feasible in carefully selected young patients with bulky stage IB1 disease. Recently, a number of molecular pathways have been identified as potential therapeutic targets. Bevacizumab - an inhibitor of vascular endothelial growth factor - is associated with improved survival in patients with recurrent/metastatic cervical cancer. Whether bevacizumab and other similar novel agents targeting molecular pathways could be used in front-line treatment along with cytotoxic chemotherapy is likely to be an area of research in future studies. PMID:27464068

  14. A prospective evaluation of the combined helical tomotherapy and chemotherapy in pediatric patients with unresectable rhabdomyosarcoma of the temporal bone.

    PubMed

    Zhang, Xinxin; Ma, Kun; Wang, Jaling; Wu, Wenming; Ma, Lin; Huang, Deliang

    2014-09-01

    We determined the efficacy of combined helical tomotherapy (HT) and chemotherapy in primary/recurrent unresectable rhabdomyosarcoma (RMS) of temporal bone. For this purpose, 9 patients (7 males/2 females), aged 4-9 (average: 6.89) years, with unresectable embryonal RMS of the temporal bone were treated at our hospital. The tumors had either invaded the carotid artery in the cavernous sinus (7/9) or both the cavernous sinus and the skull base foramen (2/9); 7 patients had primary and 2 had recurrent RMS. All patients underwent 2 cycles of induction chemotherapy with VIE (vincristine, ifosfamide, and etoposide), followed by concurrent HT (50-70 Gy) and chemotherapy with VE (vincristine and etoposide for 2 cycles), and 11 cycles of adjuvant chemotherapy with VIE. As a result, all patients achieved complete response, and the 2-year tumor-free survival rate was 100 %. During a follow-up of 3-51 months, all 9 patients were alive. We, therefore, conclude that the induction chemotherapy, adjuvant chemotherapy with VIE and concurrent HT and chemotherapy with VE regimen is effective in treating unresectable embryonal RMS of the temporal bone. The combined modality treatment may achieve the best chance of cure for these patients, thereby changing the therapeutic strategy from palliative to possibly curative. PMID:24619819

  15. Identification of a novel putative mitochondrial protein FAM210B associated with erythroid differentiation.

    PubMed

    Kondo, Aiko; Fujiwara, Tohru; Okitsu, Yoko; Fukuhara, Noriko; Onishi, Yasushi; Nakamura, Yukio; Sawada, Kenichi; Harigae, Hideo

    2016-04-01

    The transcription factor GATA-1 plays an essential role in erythroid differentiation. To identify novel GATA-1 target genes, we analyzed a merged ChIP-seq and expression profiling dataset. We identified FAM210B as a putative novel GATA-1 target gene. Study results demonstrated that GATA-1 directly regulates FAM210B expression, presumably by binding to an intronic enhancer region. Both human and murine FAM210B are abundantly expressed in the later stages of erythroblast development. Moreover, the deduced amino acid sequence predicted that FAM210B is a membrane protein, and Western blot analysis demonstrated its mitochondrial localization. Loss-of-function analysis in erythroid cells suggested that FAM210B may be involved in erythroid differentiation. The identification and characterization of FAM210B provides new insights in the study of erythropoiesis and hereditary anemias. PMID:26968549

  16. Managing Chemotherapy Side Effects: Infection

    MedlinePlus

    ... ational C ancer I nstitute Managing Chemotherapy Side Effects Infection “I am extra careful to stay away ... doctor or nurse right away. Managing Chemotherapy Side Effects: Infection Take these steps to lower your chances ...

  17. Managing Chemotherapy Side Effects: Diarrhea

    MedlinePlus

    ... ational C ancer I nstitute Managing Chemotherapy Side Effects U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES National ... before taking medicine for diarrhea. Managing Chemotherapy Side Effects: Diarrhea These foods and drinks may help if ...

  18. Survival After Chemoradiation in Resected Pancreatic Cancer: The Impact of Adjuvant Gemcitabine

    SciTech Connect

    Baschnagel, Andrew; Shah, Chirag; Margolis, Jeffrey; Nadeau, Laura; Stein, Julie; Jury, Robert; Robertson, John M.

    2012-07-01

    Purpose: To evaluate survival in patients with resected pancreatic cancer treated with concurrent chemoradiation with or without adjuvant gemcitabine (Gem). Methods and Materials: From 1998 to 2010, 86 patients with pancreatic adenocarcinoma who underwent resection were treated with adjuvant concurrent chemoradiation. Thirty-four patients received concurrent 5-fluorouracil-based chemoradiation (5-FU/RT) with traditional field radiation (range, 45-61.2 Gy; median, 50.4 Gy) without further adjuvant therapy. Thirty patients received traditional field 5-FU/RT (range, 45-60.4 Gy; median, 50.4 Gy) with Gem (1,000 mg/m{sup 2} weekly) either before and after radiotherapy or only after radiotherapy. Twenty-two patients received concurrent full-dose Gem (1,000 mg/m{sup 2} weekly)-based chemoradiation (Gem/RT), consisting of involved-field radiation (range, 27-38 Gy; median, 36 Gy) followed by further adjuvant Gem. Results: The median age of the cohort was 65 years (range, 40-80 years). Of the patients, 58 had T3 tumors (67%), 22 had T2 tumors (26%), and 6 had T1 tumors (7%). N1 disease was present in 61 patients (71%), whereas 18 patients (21%) had R1 resections. Performance status, lymph node status, and margin status were all similar among the treatment groups. Median follow-up was 19.0 months. Median overall survival (OS) (19.2 months, 19.0 months, and 21.0 months) and 3-year OS rates (26.5%, 27.2%, and 32.1%) were similar among patients with 5-FU/RT with no adjuvant Gem, those with 5-FU/RT with adjuvant Gem, and those with Gem/RT with adjuvant Gem, respectively (p = 0.88). Patients who received adjuvant Gem had a similar median OS (22.1 months) and 3-year OS rate (29%) compared to patients who did not (19.2 months and 26.5%, respectively) (p = 0.62). There was a trend for improved 3-year OS rates in patients with R0 vs. R1 resections (28.1% vs. 14.2%, p = 0.06) and in patients with T1 and T2 vs. T3 tumors (38% vs. 20%, p = 0.09). Node-negative patients had an improved 3

  19. [A case of recurrent gastric cancer successfully treated with TS-1+CDDP chemotherapy].

    PubMed

    Ogasawara, Takeshi; Ootsuka, Yasuhiro; Nakano, Shigeharu; Shida, Takashi; Nomura, Satoru; Kin, Mirei; Takahashi, Makoto; Komatsu, Teisuke

    2014-11-01

    A 74-year-old woman underwent distal gastrectomy and D1+ α dissection for the treatment of gastric cancer (pT2a, pN2, H0, P0, M0, Stage IIIA) in February 2008. She was treated with adjuvant postoperative chemotherapy consisting of TS-1. However, 32 months after the operation, paraaortic lymph node recurrence was confirmed by computed tomography (CT). She was treated with combined TS-1 and cisplatin chemotherapy. After 14 courses, CT revealed that the paraaortic lymph node metastasis had disappeared, and a complete response was attained. The patient is currently disease-free, 6 years after the operation. PMID:25731546

  20. A Pediatric Case of Metastatic Conventional Parosteal Osteosarcoma Treated With Multidrug Chemotherapy.

    PubMed

    Nodomi, Seishiro; Umeda, Katsutsugu; Okamoto, Takeshi; Saida, Satoshi; Hiramatsu, Hidefumi; Watanabe, Ken-Ichiro; Adachi, Souichi; Heike, Toshio

    2016-08-01

    Parosteal osteosarcoma (POS) is conventionally a low-grade sarcoma with limited metastatic potential; however, the tumor occasionally transforms into a high-grade dedifferentiated POS, which commonly metastasizes to distant organs. The present report describes a rare pediatric case of conventional POS with no dedifferentiated component yet had multiple pulmonary metastases at initial diagnosis. Following limb-sparing surgery and osteosarcoma-oriented neoadjuvant chemotherapy, the patient received total resection of pulmonary metastases. Despite no treatment for pulmonary recurrence 1 year after adjuvant chemotherapy, the patient is alive with stable disease 4 years and 6 months after the initial diagnosis. PMID:27149276

  1. Factors Influencing Chemotherapy Goal Perception in Newly Diagnosed Cancer Patients.

    PubMed

    Gumusay, Ozge; Cetin, Bulent; Benekli, Mustafa; Gurcan, Gamze; Ilhan, Mustafa N; Bostankolu, Basak; Ozet, Ahmet; Uner, Aytug; Coskun, Ugur; Buyukberber, Suleyman

    2016-06-01

    Cancer patients who start receiving chemotherapy have difficulty in understanding the state of their disease, the prognosis, and the purpose of treatment. We used a survey to evaluate the extent of perception of chemotherapy goal among cancer patients. Two hundred sixteen cancer patients who received chemotherapy for the first time participated in the study. The presence of depression and anxiety was assessed using the "Hospital Anxiety and Depression Scale" (HAD). The consistency between the patients' perception of the chemotherapy goal and the physician's perception was described as "right," and the inconsistency was described as "wrong." Among the patients who participated in the survey, 53.2 % (n = 115) were receiving adjuvant treatment and 46.8 % (n = 101) were receiving palliative treatment for metastatic disease. The rate of right and wrong perception of the chemotherapy goal was 51.9 % (n = 108) and 32.2 % (n = 67), respectively, and the rate of confused patients was 18.9 % (n = 41). The level of education was shown to be the only parameter involved in accurate perception of the treatment purpose (hazard ratio (HR) = 0.444, p = 0.025, 95 % confidence interval (CI) 0.219-0.903). In this study, there was a 51.9 % consistency between the physician's perception and that of the patient regarding the purpose of treatment. We demonstrated that the level of education was the unique factor in accurate perception of chemotherapy goal among cancer patients. PMID:25851203

  2. FAM46 proteins are novel eukaryotic non-canonical poly(A) polymerases.

    PubMed

    Kuchta, Krzysztof; Muszewska, Anna; Knizewski, Lukasz; Steczkiewicz, Kamil; Wyrwicz, Lucjan S; Pawlowski, Krzysztof; Rychlewski, Leszek; Ginalski, Krzysztof

    2016-05-01

    FAM46 proteins, encoded in all known animal genomes, belong to the nucleotidyltransferase (NTase) fold superfamily. All four human FAM46 paralogs (FAM46A, FAM46B, FAM46C, FAM46D) are thought to be involved in several diseases, with FAM46C reported as a causal driver of multiple myeloma; however, their exact functions remain unknown. By using a combination of various bioinformatics analyses (e.g. domain architecture, cellular localization) and exhaustive literature and database searches (e.g. expression profiles, protein interactors), we classified FAM46 proteins as active non-canonical poly(A) polymerases, which modify cytosolic and/or nuclear RNA 3' ends. These proteins may thus regulate gene expression and probably play a critical role during cell differentiation. A detailed analysis of sequence and structure diversity of known NTases possessing PAP/OAS1 SBD domain, combined with state-of-the-art comparative modelling, allowed us to identify potential active site residues responsible for catalysis and substrate binding. We also explored the role of single point mutations found in human cancers and propose that FAM46 genes may be involved in the development of other major malignancies including lung, colorectal, hepatocellular, head and neck, urothelial, endometrial and renal papillary carcinomas and melanoma. Identification of these novel enzymes taking part in RNA metabolism in eukaryotes may guide their further functional studies. PMID:27060136

  3. FAM46 proteins are novel eukaryotic non-canonical poly(A) polymerases

    PubMed Central

    Kuchta, Krzysztof; Muszewska, Anna; Knizewski, Lukasz; Steczkiewicz, Kamil; Wyrwicz, Lucjan S.; Pawlowski, Krzysztof; Rychlewski, Leszek; Ginalski, Krzysztof

    2016-01-01

    FAM46 proteins, encoded in all known animal genomes, belong to the nucleotidyltransferase (NTase) fold superfamily. All four human FAM46 paralogs (FAM46A, FAM46B, FAM46C, FAM46D) are thought to be involved in several diseases, with FAM46C reported as a causal driver of multiple myeloma; however, their exact functions remain unknown. By using a combination of various bioinformatics analyses (e.g. domain architecture, cellular localization) and exhaustive literature and database searches (e.g. expression profiles, protein interactors), we classified FAM46 proteins as active non-canonical poly(A) polymerases, which modify cytosolic and/or nuclear RNA 3′ ends. These proteins may thus regulate gene expression and probably play a critical role during cell differentiation. A detailed analysis of sequence and structure diversity of known NTases possessing PAP/OAS1 SBD domain, combined with state-of-the-art comparative modelling, allowed us to identify potential active site residues responsible for catalysis and substrate binding. We also explored the role of single point mutations found in human cancers and propose that FAM46 genes may be involved in the development of other major malignancies including lung, colorectal, hepatocellular, head and neck, urothelial, endometrial and renal papillary carcinomas and melanoma. Identification of these novel enzymes taking part in RNA metabolism in eukaryotes may guide their further functional studies. PMID:27060136

  4. Extended Adjuvant Therapy for Breast Cancer

    Cancer.gov

    An NCI Cancer Currents blog on findings from a recent clinical trial which showed that extending adjuvant therapy with an aromatase inhibitor can have important benefits for some women with early-stage cancer.

  5. Adjuvant Bisphosphonates for Postmenopausal Breast Cancer

    Cancer.gov

    A summary of a meta-analysis of randomized trials of bisphosphonates as adjuvant therapy for women with early-stage breast cancer that shows the drugs can reduce the rate of disease recurrence in bone.

  6. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in gastric cancer

    PubMed Central

    Seshadri, Ramakrishnan Ayloor; Glehen, Olivier

    2016-01-01

    Gastric cancer associated peritoneal carcinomatosis (GCPC) has a poor prognosis with a median survival of less than one year. Systemic chemotherapy including targeted agents has not been found to significantly increase the survival in GCPC. Since recurrent gastric cancer remains confined to the abdominal cavity in many patients, regional therapies like aggressive cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been investigated for GCPC. HIPEC has been used for three indications in GC- as an adjuvant therapy after a curative surgery, HIPEC has been shown to improve survival and reduce peritoneal recurrences in many randomised trials in Asian countries; as a definitive treatment in established PC, HIPEC along with CRS is the only therapeutic modality that has resulted in long-term survival in select groups of patients; as a palliative treatment in advanced PC with intractable ascites, HIPEC has been shown to control ascites and reduce the need for frequent paracentesis. While the results of randomised trials of adjuvant HIPEC from western centres are awaited, the role of HIPEC in the treatment of GCPC is still evolving and needs larger studies before it is accepted as a standard of care. PMID:26811651

  7. Role of chemotherapy in patients with soft tissue sarcomas.

    PubMed

    Maki, Robert G

    2004-04-01

    The management of soft tissue sarcomas has been highlighted in the last few years by the responsiveness of gastrointestinal stromal tumors to imatinib (Gleevec, Novartis). In this article, the use of chemotherapeutic agents in the management of this and some of the 50 or more subtypes of sarcomas are discussed, and a brief review of the use of chemotherapy in the adjuvant or neoadjuvant setting for people with large extremity sarcomas is provided. Doxorubicin and ifosfamide (Mitoxana, Bristol-Myers Squibb) remain the best individual drugs for sarcomas overall, although dacarbazine and gemcitabine (Gemzar, Eli Lilly) with or without a taxane has activity in at least a subset of sarcomas. The data regarding adjuvant chemotherapy for extremity soft tissue sarcomas is still quite mixed, with little if any overall survival advantage found to support its incorporation into disease management. The finding of tyrosine kinase inhibitors such as imatinib with demonstrated activity in gastrointestinal stromal tumors and dermatofibrosarcoma protuberans, as well as the finding of new agents such as ecteinascidin-743 (Yondelis, PharmaMar) with at least some activity against soft tissue sarcomas, reinforces the idea that we should target individual subtypes of sarcoma, just as treatment varies by subtype for the hematological malignancies. PMID:15056053

  8. Applications of nanomaterials as vaccine adjuvants

    PubMed Central

    Zhu, Motao; Wang, Rongfu; Nie, Guangjun

    2014-01-01

    Vaccine adjuvants are applied to amplify the recipient's specific immune responses against pathogen infection or malignancy. A new generation of adjuvants is being developed to meet the demands for more potent antigen-specific responses, specific types of immune responses, and a high margin of safety. Nanotechnology provides a multifunctional stage for the integration of desired adjuvant activities performed by the building blocks of tailor-designed nanoparticles. Using nanomaterials for antigen delivery can provide high bioavailability, sustained and controlled release profiles, and targeting and imaging properties resulting from manipulation of the nanomaterials’ physicochemical properties. Moreover, the inherent immune-regulating activity of particular nanomaterials can further promote and shape the cellular and humoral immune responses toward desired types. The combination of both the delivery function and immunomodulatory effect of nanomaterials as adjuvants is thought to largely benefit the immune outcomes of vaccination. In this review, we will address the current achievements of nanotechnology in the development of novel adjuvants. The potential mechanisms by which nanomaterials impact the immune responses to a vaccine and how physicochemical properties, including size, surface charge and surface modification, impact their resulting immunological outcomes will be discussed. This review aims to provide concentrated information to promote new insights for the development of novel vaccine adjuvants. PMID:25483497

  9. Use of Adjuvant 5-Fluorouracil and Radiation Therapy After Gastric Cancer Resection Among the Elderly and Impact on Survival

    SciTech Connect

    Strauss, Joshua; Hershman, Dawn L.; Buono, Donna; McBride, Russell; Clark-Garvey, Sean; Woodhouse, Shermian A.; Abrams, Julian A.

    2010-04-15

    Purpose: In randomized trials patients with resected nonmetastatic gastric cancer who received adjuvant chemotherapy and radiotherapy (chemoRT) had better survival than those who did not. We investigated the effectiveness of adjuvant chemoRT after gastric cancer resection in an elderly general population and its effects by stage. Methods and Materials: We identified individuals in the Surveillance, Epidemiology, and End Results-Medicare database aged 65 years or older with Stage IB through Stage IV (M0) gastric cancer, from 1991 to 2002, who underwent gastric resection, using multivariate modeling to analyze predictors of chemoRT use and survival. Results: Among 1,993 patients who received combined chemoRT or no adjuvant therapy after resection, having a later year of diagnosis, having a more advanced stage, being younger, being white, being married, and having fewer comorbidities were associated with combined treatment. Among 1,476 patients aged less than 85 years who survived more than 4 months, the 313 who received combined treatment had a lower mortality rate (hazard ratio, 0.83; 95% confidence interval, 0.71-0.98) than the 1,163 who received surgery alone. Adjuvant therapy significantly reduced the mortality rate for Stages III and IV (M0), trended toward improved survival for Stage II, and showed no benefit for Stage IB. We observed trends toward improved survival in all age categories except 80 to 85 years. Conclusions: The association of combined adjuvant chemoRT with improved survival in an overall analysis of Stage IB through Stage IV (M0) resected gastric cancer is consistent with clinical trial results and suggests that, in an elderly population, adjuvant chemoradiotherapy is effective. However, our observational data suggest that adjuvant treatment may not be effective for Stage IB cancer, is possibly appropriate for Stage II, and shows significant survival benefits for Stages III and IV (M0) for those aged less than 80 years.

  10. Impact of margin status and lymphadenectomy on clinical outcomes in resected pancreatic adenocarcinoma: implications for adjuvant radiotherapy

    PubMed Central

    Osipov, Arsen; Naziri, Jason; Hendifar, Andrew; Dhall, Deepti; Rutgers, Joanne K.; Chopra, Shefali; Li, Quanlin; Tighiouart, Mourad; Annamalai, Alagappan; Nissen, Nicholas N.

    2016-01-01

    Background Adjuvant chemoradiotherapy (CRT) in the treatment of pancreatic ductal adenocarcinoma (PDA) is controversial. Minimal data exists regarding the clinical significance of margin clearance distance and lymph node (LN) parameters, such as extent of dissection and LN ratio. We assessed the impact of these variables on clinical outcomes to more clearly define the subset of patients who may benefit from adjuvant radiotherapy (RT). Methods We identified 106 patients with resected stage 1-3 PDA from 2007-2013. Resection margins were categorized as positive (tumor at ink), ≤1, or >1 mm. LN evaluation included total number examined (NE), number of positive nodes (NP), ratio of NP to NE (NR), extent of dissection, and positive periportal LNs. The impact of these variables was assessed on disease-free survival (DFS) and overall survival (OS) using multivariate cox proportional hazards modeling. Results In patients receiving adjuvant chemotherapy (CT) alone, greater margin clearance led to improved DFS (P=0.0412, HR =0.51). Range of NE was 4-37, with a mean of 19. NE was not associated with DFS or OS, yet absolute NP of 5 or more was associated with a significantly worse DFS (P=0.005). Whereas periportal lymphadenectomy did not result in improved DFS or OS, patients with positive periportal LN had worse clinical outcomes (DFS, P=0.0052; OS, P=0.023). The use of adjuvant CRT was associated with improved OS (P=0.049; HR=0.29). Conclusions In patients receiving adjuvant CT alone, there was a clinically significant benefit to clearing the surgical margin beyond tumor at ink. Having ≥5 NP and positive periportal LN led to significantly worse clinical outcomes. The addition of adjuvant RT to CT in resected PDA improved OS. A comprehensive evaluation of resection margin distance and LN parameters may identify more patients at risk for locoregional failure who may benefit from adjuvant CRT. PMID:27034792

  11. Transoral Laser Microsurgery (TLM) ± Adjuvant Therapy for Advanced Stage Oropharyngeal Cancer: Outcomes and Prognostic Factors

    PubMed Central

    Rich, Jason T.; Milov, Simon; Lewis, James S.; Thorstad, Wade L.; Adkins, Douglas R.; Haughey, Bruce H.

    2013-01-01

    Objectives/Hypothesis Document survival, prognostic variables, and functional outcomes of patients with AJCC stage III or IV oropharyngeal cancer, treated with transoral laser microsurgery (TLM) ± adjuvant therapy. Study Design Analysis of prospectively assembled data pertaining to the above-described patient cohort. Methods Patients treated with TLM for AJCC stage III or IV oropharyngeal cancer at Washington University School of Medicine from 1996 to 2006 were followed for a minimum of 2 years. Recurrence, survival, functional, and human papilloma virus data were analyzed. Results Eighty-four patients met inclusion criteria. Mean follow-up was 52.6 months. Overall AJCC stages were: III 15% and IV 85%. T stages were T1–2, 74%; T3–4, 26%. Eighty-three patients underwent neck dissection, 50 received adjuvant radiotherapy, and 28 received adjuvant chemoradiotherapy. Overall survival at 2 and 5 years was 94% and 88%, respectively. Disease-specific survival at 2 and 5 years was 96% and 92%, respectively. Six patients recurred (7%): locally (one), regionally (four), and distant (five). T stage, positive margins, and p16 status significantly impacted survival. The addition of adjuvant chemo-therapy in high-risk patients did not significantly impact survival. Five patients (6%) had major surgical complications, but without mortality. Eighty-one percent of patients had acceptable swallowing function at last follow-up. Immediately postoperatively, 17% required G-tubes, which dropped to 3.4% of living patients at 3 years. Conclusions In this population, our findings validate TLM ± adjuvant therapy as a highly effective strategy for survival, locoregional control, and swallowing recovery in AJCC stage III and IV oropharyngeal cancer. Our finding also show that p16 positivity improves survival. PMID:19572271

  12. Survival of women with clear cell and papillary serous endometrial cancer after adjuvant radiotherapy

    PubMed Central

    2014-01-01

    Background Type II (papillary serous and clear cell) endometrial carcinoma (EC) is a rare subgroup and is considered to have an unfavorable prognosis. The purpose of this retrospective analysis was to elucidate the meaning of adjuvant radiotherapy (RT) for clinical outcome and to define prognostic factors in these patients (pts). Methods From 2004-2012 forty-two pts with type II EC underwent surgery followed by adjuvant RT at our department. Median age was 72 years. The majority were early stage carcinomas (FIGO I n = 27 [64.3%], FIGO II n = 4 [9.5%], FIGO III n = 11 [26.2%]. Seven pts (16.7%) received adjuvant chemotherapy (ChT). Pts were treated with external beam radiotherapy (EBRT) and brachytherapy (IVB) boost. Results Five-year local recurrence free survival (LRFS), distant metastases free survival (DMFS) and overall survival (OS) were 85.4%, 78%, and 64.5% respectively. LRFS was better with lower pT stage, without lymphangiosis (L0), without haemangiosis (V0) and negative resection margins (R0). DMFS was prolonged in lymph node negatives (N0), L0, V0 and R0. OS was improved in younger pts, N0, L0, V0 and after lymphadenectomy (LNE). Multivariate analysis revealed haemangiosis (V1) as the only independent prognostic factor for OS (p = .014) and DMFS (p = .008). For LRFS pT stage remained as an independent prognostic factor (p = .028). Conclusions Adjuvant RT with EBRT/IVB ensures adequate local control in type II EC, but control rates remain lower than in type I EC. A benefit of additional adjuvant ChT could not be demonstrated and a general omission of EBRT cannot be recommended at this point. Lymphovascular infiltration and pT stage might be the best predictive factors for a benefit from combined local and systemic treatment. PMID:24941899

  13. Neoadjuvant Chemotherapy for Facilitating Surgical Resection of Infantile Massive Intracranial Immature Teratoma.

    PubMed

    Kitahara, Takahiro; Tsuji, Yoshihito; Shirase, Tomoyuki; Yukawa, Hiroyuki; Takeichi, Yasuhiro; Yamazoe, Naohiro

    2016-01-01

    Immature teratoma (IMT) is the most frequent histological subtype of infantile intracranial teratoma, the most common congenital brain tumor. IMT contains incompletely differentiated components resembling fetal tissues. Infantile intracranial IMT has a dismal prognosis, because it is often inoperable due to its massive size and high vascularity. Neoadjuvant chemotherapy has been shown to be effective in decreasing tumor volume and vascularity to facilitate surgical resection in other types of infantile brain tumors. However, only one recent case report described the effectiveness of neoadjuvant chemotherapy for infantile intracranial IMT in the literature, even though it is common entity with a poor prognosis in infants. Here, we describe the case of a 2-month-old male infant with a very large intracranial IMT. Maximal surgical resection was first attempted but was unsuccessful because of severe intraoperative hemorrhage. Neoadjuvant carboplatin and etoposide (CARE) chemotherapy was then administered with the aim of shrinking and devascularizing the tumor. After neoadjuvant chemotherapy, tumor size did not decrease, but intraoperative blood loss significantly decreased and near-total resection was achieved by the second and third surgery. The patient underwent adjuvant CARE chemotherapy and has been alive for 3 years after surgery without tumor regrowth. Even when neoadjuvant chemotherapy does not decrease tumor volume of infantile intracranial IMT, surgical resection should be tried because chemotherapy can facilitate surgical resection and improve clinical outcome by reducing tumor vascularity. PMID:27039944

  14. Survival Benefits and Trends in Use of Adjuvant Therapy Among Elderly Stage II and III Rectal Cancer Patients in the General Population

    PubMed Central

    Dobie, Sharon A.; Warren, Joan L.; Matthews, Barbara; Schwartz, David; Baldwin, Laura-Mae; Billingsley, Kevin

    2011-01-01

    BACKGROUND This study examined elderly stage II and III rectal cancer patients’ adjuvant chemoradiation therapy adherence, trends in adherence over time, and the relation of levels of adherence to mortality. METHODS The authors studied 2886 stage II and III rectal cancer patients who had surgical resection and who appeared in 1992–1999 linked SEER-Medicare claims data. The authors compared measures of adjuvant radiation and chemotherapy receipt and completion between stage II and III patients. Adjusted risk of cancer-related 5-year mortality was calculated by multivariate logistic regression for different levels of chemoradiation adherence among stage II and III patients. RESULTS Of the 2886 patients, 45.4% received both adjuvant radiation and chemotherapy. Stage III patients were more likely to receive chemoradiation than stage II patients. The receipt of chemoradiation by stage II patients increased significantly from 1992 to 1999. Stage III patients were more likely to complete radiation therapy (96.6%), chemotherapy (68.2%), and both modalities (67.5%) than stage II patients (91.5%, 49.8%, 47.6%, respectively). Only a complete course of both radiation and chemotherapy for both stage II (relative risk [RR] 0.74; 95% CI, 0.54, 0.97) and III (RR 0.80; 95% CI, 0.65, 0.96) decreased the adjusted 5-year cancer mortality risk compared with counterparts with no adjuvant therapy. CONCLUSIONS Even though stage II rectal cancer patients were less likely than stage III patients to receive and complete adjuvant chemoradiation, both patient groups in the general population had lower cancer-related mortality if they completed chemoradiation. These patients deserve support and encouragement to complete treatment. PMID:18189291

  15. Inactivation of a Novel FGF23 Regulator, FAM20C, Leads to Hypophosphatemic Rickets in Mice

    PubMed Central

    Wang, Xiaofang; Wang, Suzhen; Li, Changcheng; Gao, Tian; Liu, Ying; Rangiani, Afsaneh; Sun, Yao; Hao, Jianjun; George, Anne; Lu, Yongbo; Groppe, Jay; Yuan, Baozhi; Feng, Jian Q.; Qin, Chunlin

    2012-01-01

    Family with sequence similarity 20,-member C (FAM20C) is highly expressed in the mineralized tissues of mammals. Genetic studies showed that the loss-of-function mutations in FAM20C were associated with human lethal osteosclerotic bone dysplasia (Raine Syndrome), implying an inhibitory role of this molecule in bone formation. However, in vitro gain- and loss-of-function studies suggested that FAM20C promotes the differentiation and mineralization of mouse mesenchymal cells and odontoblasts. Recently, we generated Fam20c conditional knockout (cKO) mice in which Fam20c was globally inactivated (by crossbreeding with Sox2-Cre mice) or inactivated specifically in the mineralized tissues (by crossbreeding with 3.6 kb Col 1a1-Cre mice). Fam20c transgenic mice were also generated and crossbred with Fam20c cKO mice to introduce the transgene in the knockout background. In vitro gain- and loss-of-function were examined by adding recombinant FAM20C to MC3T3-E1 cells and by lentiviral shRNA–mediated knockdown of FAM20C in human and mouse osteogenic cell lines. Surprisingly, both the global and mineralized tissue-specific cKO mice developed hypophosphatemic rickets (but not osteosclerosis), along with a significant downregulation of osteoblast differentiation markers and a dramatic elevation of fibroblast growth factor 23 (FGF23) in the serum and bone. The mice expressing the Fam20c transgene in the wild-type background showed no abnormalities, while the expression of the Fam20c transgene fully rescued the skeletal defects in the cKO mice. Recombinant FAM20C promoted the differentiation and mineralization of MC3T3-E1 cells. Knockdown of FAM20C led to a remarkable downregulation of DMP1, along with a significant upregulation of FGF23 in both human and mouse osteogenic cell lines. These results indicate that FAM20C is a bone formation “promoter” but not an “inhibitor” in mouse osteogenesis. We conclude that FAM20C may regulate osteogenesis through its direct role in

  16. 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.

  17. Disease-Free Survival as a Surrogate for Overall Survival in Adjuvant Trials of Gastric Cancer: A Meta-Analysis

    PubMed Central

    Paoletti, Xavier; Alberts, Steven; Bang, Yung-Jue; Benedetti, Jacqueline; Bleiberg, Harry; Catalano, Paul; Lordick, Florian; Michiels, Stefan; Morita, Satoshi; Ohashi, Yasuo; Pignon, Jean-pierre; Rougier, Philippe; Sasako, Mitsuru; Sakamoto, Junichi; Sargent, Daniel; Shitara, Kohei; Cutsem, Eric Van; Buyse, Marc; Burzykowski, Tomasz

    2013-01-01

    Background In investigations of the effectiveness of surgery and adjuvant chemotherapy for gastric cancers, overall survival (OS) is considered the gold standard endpoint. However, the disadvantage of using OS as the endpoint is that it requires an extended follow-up period. We sought to investigate whether disease-free survival (DFS) is a valid surrogate for OS in trials of adjuvant chemotherapy for gastric cancer. Methods The GASTRIC group initiated a meta-analysis of individual patient data collected in randomized clinical trials comparing adjuvant chemotherapy vs surgery alone for patients with curatively resected gastric cancer. Surrogacy of DFS was assessed through the correlation between the endpoints as well as through the correlation between the treatment effects on the endpoints. External validation of the prediction based on DFS was also evaluated. Results Individual patient data from 14 randomized clinical trials that included a total of 3288 patients were analyzed. The rank correlation coefficient between DFS and OS was 0.974 (95% confidence interval [CI] = 0.971 to 0.976). The coefficient of determination between the treatment effects on DFS and on OS was as high as 0.964 (95% CI = 0.926 to 1.000), and the surrogate threshold effect based on adjusted regression analysis was 0.92. In external validation, the six hazard ratios for OS predicted according to DFS were in very good agreement with those actually observed for OS. Conclusions DFS is an acceptable surrogate for OS in trials of cytotoxic agents for gastric cancer in the adjuvant setting. PMID:24108812

  18. Efficacy of Adjuvant 5-Fluorouracil Therapy for Patients with EMAST-Positive Stage II/III Colorectal Cancer

    PubMed Central

    Hamaya, Yasushi; Guarinos, Carla; Tseng-Rogenski, Stephanie S.; Iwaizumi, Moriya; Das, Ritabrata; Jover, Rodrigo; Castells, Antoni; Llor, Xavier; Andreu, Montserrat; Carethers, John M.

    2015-01-01

    Elevated Microsatellite Alterations at Selected Tetranucleotide repeats (EMAST) is a genetic signature found in up to 60% of colorectal cancers (CRCs) that is caused by somatic dysfunction of the DNA mismatch repair (MMR) protein hMSH3. We have previously shown in vitro that recognition of 5-fluorouracil (5-FU) within DNA and subsequent cytotoxicity was most effective when both hMutSα (hMSH2-hMSH6 heterodimer) and hMutSβ (hMSH2-hMSH3 heterodimer) MMR complexes were present, compared to hMutSα > hMutSβ alone. We tested if patients with EMAST CRCs (hMutSβ defective) had diminished response to adjuvant 5-FU chemotherapy, paralleling in vitro findings. We analyzed 230 patients with stage II/III sporadic colorectal cancers for which we had 5-FU treatment and survival data. Archival DNA was analyzed for EMAST (>2 of 5 markers mutated among UT5037, D8S321, D9S242, D20S82, D20S85 tetranucleotide loci). Kaplan-Meier survival curves were generated and multivariate analysis was used to determine contribution to risk. We identified 102 (44%) EMAST cancers. Ninety-four patients (41%) received adjuvant 5-FU chemotherapy, and median follow-up for all patients was 51 months. Patients with EMAST CRCs demonstrated improved survival with adjuvant 5FU to the same extent as patients with non-EMAST CRCs (P<0.05). We observed no difference in survival between patients with stage II/III EMAST and non-EMAST cancers (P = 0.36). There is improved survival for stage II/III CRC patients after adjuvant 5-FU-based chemotherapy regardless of EMAST status. The loss of contribution of hMSH3 for 5-FU cytotoxicity may not adversely affect patient outcome, contrasting patients whose tumors completely lack DNA MMR function (MSI-H). PMID:25996601

  19. Efficacy and Interaction of Antioxidant Supplements as Adjuvant Therapy in Cancer Treatment: A Systematic Review.

    PubMed

    Yasueda, Asuka; Urushima, Hayato; Ito, Toshinori

    2016-03-01

    Oxidative stress is a key component in carcinogenesis. Although radiation produces reactive oxygen species, some anticancer agents such as alkylating agents, platinum and antitumor antibiotics exert cytotoxicity by generating free radicals. Nonenzymatic exogenous antioxidants such as vitamins, minerals, and polyphenols can quench ROS activity. However, whether antioxidants alter antitumor effects during radiotherapy and some types of chemotherapy remains unclear. In the present study, we reviewed antioxidants as an adjuvant therapy for cancer patients during chemotherapy or radiotherapy. Electronic literature searches were performed to select all randomized controlled clinical trials (RCTs) in which antioxidants were administered to cancer patients along with chemotherapy or radiotherapy. Articles or abstracts written in English were included. In total, 399 reports received primary screening. Duplicated articles and those meeting the exclusion criteria (not RCT, not human, and no oral administration) were excluded. Finally, 49 reports matching the inclusion criteria were included. It was difficult to determine whether antioxidants affect treatment outcomes or whether antioxidants ameliorate adverse effects induced by chemotherapy and radiotherapy. It is desirable to use an evidence-based method to select supplements best suited to cancer patients. Although there are many opinions about risks or benefits of antioxidant supplementation, we could mostly conclude that the harm caused by antioxidant supplementation remains unclear for patients during cancer therapy, except for smokers undergoing radiotherapy. PMID:26503419

  20. Adjuvant effects of saponins on animal immune responses*

    PubMed Central

    Rajput, Zahid Iqbal; Hu, Song-hua; Xiao, Chen-wen; Arijo, Abdullah G.

    2007-01-01

    Vaccines require optimal adjuvants including immunopotentiator and delivery systems to offer long term protection from infectious diseases in animals and man. Initially it was believed that adjuvants are responsible for promoting strong and sustainable antibody responses. Now it has been shown that adjuvants influence the isotype and avidity of antibody and also affect the properties of cell-mediated immunity. Mostly oil emulsions, lipopolysaccharides, polymers, saponins, liposomes, cytokines, ISCOMs (immunostimulating complexes), Freund’s complete adjuvant, Freund’s incomplete adjuvant, alums, bacterial toxins etc., are common adjuvants under investigation. Saponin based adjuvants have the ability to stimulate the cell mediated immune system as well as to enhance antibody production and have the advantage that only a low dose is needed for adjuvant activity. In the present study the importance of adjuvants, their role and the effect of saponin in immune system is reviewed. PMID:17323426

  1. Outcomes of Adjuvant Chemoradiation After Pancreaticoduodenectomy With Mesenterico-Portal Vein Resection for Adenocarcinoma of the Pancreas

    SciTech Connect

    Hristov, Boris; Reddy, Sushanth; Lin, Steven H.; Cameron, John L.; Pawlik, Timothy M.; Hruban, Ralph H.; Swartz, Michael J.; Edil, Barish H.; Kemp, Clinton; Wolfgang, Christopher L.; Herman, Joseph M.

    2010-01-15

    Purpose: Surgery followed by chemotherapy and radiation (CRT) offers patients with pancreatic adenocarcinoma a chance for extended survival. In some patients, however, resection is difficult because of vascular involvement by the carcinoma, necessitating resection and grafting of the mesenterico-portal vessels. The purpose of this study was to compare outcomes between pancreaticoduodenectomy (PD) with and without mesenterico-portal vein resection (VR) in patients receiving adjuvant CRT for pancreatic adenocarcinoma. Methods and Materials: Between 1993 and 2005, 160 patients underwent PD with 5-FU-based adjuvant CRT followed by maintenance chemotherapy at the Johns Hopkins Hospital; 20 (12.5%) of the 160 underwent VR. Clinical outcomes, including median survival, overall survival, and complication rates were assessed for both groups. Results: Patients who underwent VR had significantly longer operative times (p = 0.009), greater intraoperative blood loss (p = 0.01), and longer postoperative lengths of stay (p = 0.03). However, postoperative morbidity, median survival, and overall survival rates were similar between the two groups. Most patients (70%) from both groups were able to complete CRT, and a subgroup analysis demonstrated no appreciable differences in terms of complications. None of the VR patients who received adjuvant CRT developed veno-occlusive disease or graft failure/leakage. Conclusion: In a cohort of patients treated with adjuvant 5-FU-based CRT at the Johns Hopkins Hospital, having a VR at the time of PD resulted in similar complication rates and survival. These data support the feasibility and safety of adjuvant CRT in patients undergoing VR at the time of PD.

  2. Radiation Therapy Is Associated With Improved Survival in the Adjuvant and Definitive Treatment of Intrahepatic Cholangiocarcinoma

    SciTech Connect

    Shinohara, Eric T. Mitra, Nandita; Guo Mengye; Metz, James M.

    2008-12-01

    Purpose: Intrahepatic cholangiocarcinomas (IHC) are rare tumors for which large randomized studies regarding the use of radiation are not available. The purpose of this study was to examine the role of adjuvant and definitive radiation therapy in the treatment of IHC in a large group of patients. Methods and Materials: This is a retrospective analysis of 3,839 patients with IHC collected from the Surveillance, Epidemiology, and End Results (SEER) database. The primary endpoint was overall survival (OS). Results: Patients received either surgery alone (25%), radiation therapy alone (10%), surgery and adjuvant radiation therapy (7%) or no treatment (58%). The median age of the patient population was 73 years (range, 22-102 years); 52% of patients were male and 81% were Caucasian. Median OS was 11 (95% confidence interval [CI], 9-13), 6 (95% CI, 5-6), 7 (95% CI, 6-8), and 3 months for surgery and adjuvant radiation therapy, sugery alone, radiation therapy alone, and no treatment, respectively. The OS was significantly different between surgery alone and surgery and adjuvant radiation therapy (p = 0.014) and radiation therapy alone and no treatment (p < 0.0001). Use of surgery and adjuvant radiation therapy conferred the greatest benefit on OS (HR = 0.40; 95% CI, 0.34-0.47), followed by surgery alone (hazard ratio [HR], 0.49; 95% CI, 0.44-0.54) and radiation therapy alone (HR, 0.68; 95% CI, 0.59-0.77) compared with no treatment, on multivariate analysis. Propensity score adjusted hazard ratios (controlling for age, race/ethnicity, stage, and year of diagnosis) were also significant (surgery and adjuvant radiation therapy vs. surgery alone (HR, 0.82; 95% CI, 0.70-0.96); radiation therapy alone vs. no treatment (HR, 0.67; 95% CI, 0.58-0.76)). Conclusions: The study results suggest that adjuvant and definitive radiation treatment prolong survival, although cure rates remain low. Future studies should evaluate the addition of chemotherapy and biologics to the treatment of

  3. Synthetic Self-Adjuvanting Glycopeptide Cancer Vaccines

    NASA Astrophysics Data System (ADS)

    Payne, Richard; McDonald, David; Byrne, Scott

    2015-10-01

    Due to changes in glycosyltransferase expression during tumorigenesis, the glycoproteins of cancer cells often carry highly truncated carbohydrate chains compared to those on healthy cells. These glycans are known as tumor-associated carbohydrate antigens, and are prime targets for use in vaccines for the prevention and treatment of cancer. Herein, we review the state-of-the-art in targeting the immune system towards tumor-associated glycopeptide antigens via synthetic self adjuvanting vaccines, in which the antigenic and adjuvanting moieties of the vaccines are present in the same molecule. The majority of the self-adjuvanting glycopeptide cancer vaccines reported to date employ antigens from mucin 1, a protein which is highly over-expressed and aberrantly glycosylated in many forms of cancer. The adjuvants used in these vaccines predominantly include lipopeptide- or lipoamino acid-based TLR2 agonists, although studies investigating stimulation of TLR9 and TLR4 are also discussed. Most of these adjuvants are highly lipophilic, and, upon conjugation to antigenic peptides, provide amphiphilic vaccine molecules. The amphiphilic nature of these vaccine constructs can lead to the formation of higher-order structures by vaccines in solution, which are likely to be important for their efficacy in vivo.

  4. Beyond antigens and adjuvants: formulating future vaccines.

    PubMed

    Moyer, Tyson J; Zmolek, Andrew C; Irvine, Darrell J

    2016-03-01

    The need to optimize vaccine potency while minimizing toxicity in healthy recipients has motivated studies of the formulation of vaccines to control how, when, and where antigens and adjuvants encounter immune cells and other cells/tissues following administration. An effective subunit vaccine must traffic to lymph nodes (LNs), activate both the innate and adaptive arms of the immune system, and persist for a sufficient time to promote a mature immune response. Here, we review approaches to tailor these three aspects of vaccine function through optimized formulations. Traditional vaccine adjuvants activate innate immune cells, promote cell-mediated transport of antigen to lymphoid tissues, and promote antigen retention in LNs. Recent studies using nanoparticles and other lymphatic-targeting strategies suggest that direct targeting of antigens and adjuvant compounds to LNs can also enhance vaccine potency without sacrificing safety. The use of formulations to regulate biodistribution and promote antigen and inflammatory cue co-uptake in immune cells may be important for next-generation molecular adjuvants. Finally, strategies to program vaccine kinetics through novel formulation and delivery strategies provide another means to enhance immune responses independent of the choice of adjuvant. These technologies offer the prospect of enhanced efficacy while maintaining high safety profiles necessary for successful vaccines. PMID:26928033

  5. CpG DNA as mucosal adjuvant.

    PubMed

    McCluskie, M J; Davis, H L

    1999-09-01

    We have previously found synthetic oligodeoxynucleotides (ODN) containing immunostimulatory CpG motifs to be a potent adjuvant to protein administered by intramuscular injection or intranasal inhalation to BALB/c mice. Herein we have further evaluated the potential of CpG ODN as a mucosal adjuvant to purified hepatitis B surface antigen (HBsAg) when administered alone or with cholera toxin (CT). CpG ODN and CT both augmented systemic (humoral and cellular) and mucosal immune responses against HBsAg, and these could be further enhanced with higher doses of adjuvant or boosting. Overall, antibody isotypes with CT alone were predominantly IgG1 (Th2-like) whereas they were predominantly IgG2a (Th1-like) with CpG ODN alone or in combination with CT. Results from this study indicate that stimulatory CpG ODN are promising new adjuvants for mucosal vaccination strategies, whether used alone or in combination with other mucosal adjuvants. PMID:10506647

  6. Impact of adjuvant treatment modalities on survival outcomes in curatively resected pancreatic and periampullary adenocarcinoma

    PubMed Central

    Benekli, Mustafa; Unal, Olcun Umit; Unek, İlkay Tugba; Tastekin, Didem; Dane, Faysal; Algın, Efnan; Ulger, Sukran; Eren, Tulay; Topcu, Turkan Ozturk; Turkmen, Esma; Babacan, Nalan Akgül; Tufan, Gulnihal; Urakci, Zuhat; Ustaalioglu, Basak Oven; Uysal, Ozlem Sonmez; Ercelep, Ozlem Balvan; Taskoylu, Burcu Yapar; Aksoy, Asude; Canhoroz, Mustafa; Demirci, Umut; Dogan, Erkan; Berk, Veli; Balakan, Ozan; Ekinci, Ahmet Şiyar; Uysal, Mukremin; Petekkaya, İbrahim; Ozturk, Selçuk Cemil; Tonyalı, Önder; Çetin, Bülent; Aldemir, Mehmet Naci; Helvacı, Kaan; Ozdemir, Nuriye; Oztop, İlhan; Coskun, Ugur; Uner, Aytug; Ozet, Ahmet; Buyukberber, Suleyman

    2015-01-01

    Background We examined the impact of adjuvant modalities on resected pancreatic and periampullary adenocarcinoma (PAC). Methods A total of 563 patients who were curatively resected for PAC were retrospectively analyzed between 2003 and 2013. Results Of 563 patients, 472 received adjuvant chemotherapy (CT) alone, chemoradiotherapy (CRT) alone, and chemoradiotherapy plus chemotherapy (CRT-CT) were analyzed. Of the 472 patients, 231 were given CRT-CT, 26 were given CRT, and 215 were given CT. The median recurrence-free survival (RFS) and overall survival (OS) were 12 and 19 months, respectively. When CT and CRT-CT groups were compared, there was no significant difference with respect to both RFS and OS, and also there was no difference in RFS and OS among CRT-CT, CT and CRT groups. To further investigate the impact of radiation on subgroups, patients were stratified according to lymph node status and resection margins. In node-positive patients, both RFS and OS were significantly longer in CRT-CT than CT. In contrast, there was no significant difference between groups when patients with node-negative disease or patients with or without positive surgical margins were considered. Conclusions Addition of radiation to CT has a survival benefit in patients with node-positive disease following pancreatic resection. PMID:26361410

  7. Korean Medicine Therapy as a Substitute for Chemotherapy for Metastatic Breast Cancer: A Case Report

    PubMed Central

    Lee, Dong-Hyun; Kim, Sung-Su; Seong, Shin; Kim, Nari; Han, Jae-Bok

    2015-01-01

    A 46-year-old Korean woman was diagnosed with stage III breast cancer and underwent 8 cycles of neoadjuvant chemotherapy, breast conservation surgery and adjuvant radiotherapy. However, the cancer recurred in the right upper lung (RUL) and the right pulmonary hilum after 8 months. The RUL nodule was removed through a wedge resection, and the pathologic finding was revealed as a metastatic adenocarcinoma. Adjuvant chemotherapy was recommended, but she refused it because she feared adverse reactions to chemotherapy. Instead, Korean Medicine Therapy with intravenous wild ginseng pharmacopuncture (WGP), Cordyceps sinensis pharmacopuncture, Trichosanthes kirilowii pharmacopuncture, Euonymus alatus pharmacopuncture (EAP) and Astragalus membranaceus pharmacopuncture was started. After a month, the disease looked stable, but findings of newly occurring metastatic lymphadenopathies appeared on CT after 6 months. Salvage chemotherapy was recommended, but she also refused it. At this time, Prunella vulgaris pharmacopuncture was started. Finally, a complete resolution was confirmed on PET-CT after 5 months, and she has remained in stable condition for more than 6 months with WGP, EAP, a Soram nebulizer solution inhalation and the oral intake of Soramdan S and Hangamdan S. PMID:25848354

  8. Korean medicine therapy as a substitute for chemotherapy for metastatic breast cancer: a case report.

    PubMed

    Lee, Dong-Hyun; Kim, Sung-Su; Seong, Shin; Kim, Nari; Han, Jae-Bok

    2015-01-01

    A 46-year-old Korean woman was diagnosed with stage III breast cancer and underwent 8 cycles of neoadjuvant chemotherapy, breast conservation surgery and adjuvant radiotherapy. However, the cancer recurred in the right upper lung (RUL) and the right pulmonary hilum after 8 months. The RUL nodule was removed through a wedge resection, and the pathologic finding was revealed as a metastatic adenocarcinoma. Adjuvant chemotherapy was recommended, but she refused it because she feared adverse reactions to chemotherapy. Instead, Korean Medicine Therapy with intravenous wild ginseng pharmacopuncture (WGP), Cordyceps sinensis pharmacopuncture, Trichosanthes kirilowii pharmacopuncture, Euonymus alatus pharmacopuncture (EAP) and Astragalus membranaceus pharmacopuncture was started. After a month, the disease looked stable, but findings of newly occurring metastatic lymphadenopathies appeared on CT after 6 months. Salvage chemotherapy was recommended, but she also refused it. At this time, Prunella vulgaris pharmacopuncture was started. Finally, a complete resolution was confirmed on PET-CT after 5 months, and she has remained in stable condition for more than 6 months with WGP, EAP, a Soram nebulizer solution inhalation and the oral intake of Soramdan S and Hangamdan S. PMID:25848354

  9. Innovations in chemotherapy and radiation therapy: Implications and opportunities for the Asia-Pacific Rim

    PubMed Central

    Heron, DE; Shogan, JE; Mucenski, JW

    2008-01-01

    New cases of invasive cancer in the United States occur among nearly 1.5 million people annually. In 2007, more than 1,500 people died per day with this diagnosis. Cancer is responsible for nearly one in every four deaths reported in the country. Enormous amounts of money and research have been, and are being spent, in an attempt to improve these numbers. While prevention and early detection remain the key to long-term success, treatment in the neo-adjuvant, adjuvant and metastatic settings still centre around two main treatment modalities – radiation therapy and chemotherapy. This article will review the advances that have been made in both areas that are making these treatments more precise and convenient, as well as less toxic, for the patient. In the field of radiation therapy this involves the development of new therapy planning and delivery systems, such as intensity-modulated radiation therapy (IMRT), and positron emission and computed tomography, PET-CT. Chemotherapy has also evolved with the development of targeted chemotherapy for the treatment of specific malignancies as well as improved supportive care agents which allow for the administration of dose-dense chemotherapy when appropriate. PMID:21611006

  10. Adjuvant Pelvic Radiotherapy vs. Sequential Chemoradiotherapy for High-Risk Stage I-II Endometrial Carcinoma

    PubMed Central

    El-Hadaad, Hend Ahmed; Wahba, Hanan Ahmed; Gamal, Anas Mohamed; Dawod, Tamer

    2012-01-01

    Objective To explore if the addition of adjuvant chemotherapy with paclitaxel and carboplatin to radiotherapy confers an advantage for overall survival (OAS), and progression free survival (PFS); to assess the incidence of relapses over standard pelvic radiotherapy; and to evaluate the related toxicity in high-risk stage I-II endometrial carcinoma Methods Medical records were reviewed to identify high-risk stage I-II endometrial carcinoma cases treated in the Clinical Oncology and Nuclear Medicine department between 2002 and 2008 with adjuvant radiotherapy alone (arm I) (57 patients) or with sequential carboplatin (AUC5-6) and paclitaxel (135−175 mg/m2) with radiotherapy (arm II) (51 patients). Radiotherapy was performed through the four-field box technique at doses of 45−50 Gy (1.8 Gy/day × 5 days/week). Results The toxicity was manageable and predominantly hematologic with a grade 3 neutropenia and thrombocytopenia in 9.8% and 6% of the patients in arm I and arm II, respectively, without febrile neutropenia. All patients experienced hair loss. Chemoradiotherapy arm was associated with a lower incidence rate of relapse (9.8% vs. 22.7%). After a median follow-up period of 48 months, the 5-year OAS and PFS rates for chemoradiotherapy-treated patients were significantly more favorable than those who did not receive chemotherapy (P=0.02 and 0.03, respectively). In arm I, the OAS and PFS rates were 73.7% and 66.7% compared with those in arm II, whose rates were 90.2% and 84.3%. Conclusions Adjuvant chemoradiation with paclitaxel and carboplatin improved the survival rates and decreased the recurrence rates in patients with high-risk stage I-II endometrial carcinoma. Chemotherapy was associated with an acceptable rate of toxicity. However, a prospective study with a larger number of patients is needed to define a standard adjuvant treatment for high-risk stage I-II endometrial carcinoma. PMID:23691474

  11. [Hepatic Resection of Multiple Liver Metastases from Gastric Cancer after Molecular Targeted Chemotherapy(S-1 plus Cisplatin plus Trastuzumab)].

    PubMed

    Kim, Yongkook; Hosoda, Yohei; Nishino, Masaya; Okano, Miho; Kawada, Junji; Yamasaki, Masaru; Nagai, Ken-ichi; Yasui, Masayosi; Okuyama, Masaki; Tsujinaka, Toshimasa

    2015-11-01

    A 62-year-old man was diagnosed with gastric cancer and underwent distal gastrectomy, and D1+b lymph node dissection. He was diagnosed postoperatively with T1b (sm2) N0M0, StageⅠA gastric adenocarcinoma and did not receive any adjuvant chemotherapy after surgery. One year and 6 months after gastrectomy, blood analysis indicated high levels of carcinoembryonic antigen (CEA 262.1 ng/mL) while abdominal computed tomography (CT) revealed multiple liver tumors (S7: 15 mm, S7/8: 20 mm). The patient was diagnosed with metachronous multiple liver metastases from gastric cancer. Chemotherapy, combined with molecular targeted therapy (S-1 plus cisplatin [CDDP] plus trastuzumab), was administered because of overexpression of the human epidermal growth factor receptor 2 (HER2) protein in the primary tumor as assessed by immunohistochemistry, the CEA levels decreased immediately after 2 cycles of the chemotherapy, and the liver metastases shrank markedly with no evidence of new lesions on abdominal CT. However, after treatment, Grade 3 neutropenia and diarrhea were observed. Chemotherapy was suspended and hepatic resection was performed. After hepatic resection, the liver tumors were histologically evaluated as Grade 2 metastatic gastric adenocarcinoma, and the HER2 expression of remnant carcinoma cells was established. The patient has been in good health and remained free of recurrences in the 2 years and 3 months after the liver resection. Surgery with preoperative chemotherapy (S-1 plus CDDP plus trastuzumab) can be an effective treatment for liver metastasis from HER2-positive gastric cancer. PMID:26805121

  12. Chemotherapy and fertility.

    PubMed

    Blumenfeld, Zeev

    2012-06-01

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

  13. Adjuvant radiation for soft tissue sarcomas.

    PubMed

    Dickie, Colleen I; Haas, Rick; O'Sullivan, Brian

    2015-01-01

    Over recent decades, limb-preservation surgery in combination with radiotherapy achieves local control rates exceeding 90% for extremity soft tissue sarcoma (STS). Local control is not as successful for retroperitoneal sarcoma (approximately 60%) despite aggressive surgical approaches including en bloc resection of uninvolved adjacent organs combined with intensity modulated radiotherapy (IMRT). This review will discuss the indications for adjuvant radiation therapy (RT) for primary presentation of soft tissue sarcoma: "What," referring to the type and manner of planning and delivery of RT; "When," referring to the timing and scheduling of RT; and "Why," referring to the rationale for the use of RT will be addressed. From a practical stand point, this Educational Chapter on "adjuvant RT" will focus on pre- and postoperative RT in the context of gross total resection for extremity and retroperitoneal soft tissue sarcoma, the two most frequent paradigms for the use of adjuvant RT. PMID:25993234

  14. Systemic immunotoxicity reactions induced by adjuvanted vaccines.

    PubMed

    Batista-Duharte, Alexander; Portuondo, Deivys; Pérez, O; Carlos, Iracilda Zeppone

    2014-05-01

    Vaccine safety is a topic of concern for the treated individual, the family, the health care personnel, and the others involved in vaccination programs as recipients or providers. Adjuvants are necessary components to warrant the efficacy of vaccines, however the overstimulation of the immune system is also associated with adverse effects. Local reactions are the most frequent manifestation of toxicity induced by adjuvanted vaccines and, with the exception of the acute phase response (APR), much less is known about the systemic reactions that follow vaccination. Their low frequency or subclinical expression meant that this matter has been neglected. In this review, various systemic reactions associated with immune stimulation will be addressed, including: APR, hypersensitivity, induction or worsening of autoimmune diseases, modification of hepatic metabolism and vascular leak syndrome (VLS), with an emphasis on the mechanism involved. Finally, the authors analyze the current focus of discussion about vaccine safety and opportunities to improve the design of new adjuvanted vaccines in the future. PMID:24607449

  15. [Conversion Therapy of Initially Unresectable Rectal Cancer with Perforation via FOLFOX4 Chemotherapy].

    PubMed

    Yamada, Chizu; Ishikawa, Fumihiko; Nitta, Hiroshi; Fujita, Yoshihisa; Omoto, Hideyuki; Kamata, Shigeyuki; Ito, Hiroshi

    2015-11-01

    We describe a case of perforated rectal cancer that became curatively resectable after FOLFOX4 chemotherapy. An 81- year-old woman was transferred to our hospital with a diagnosis of bowel perforation. She underwent emergency transverse colostomy, peritoneal lavage, and the insertion of indwelling drainage tubes, because the perforated rectal cancer was considered unresectable. After recuperation, she received chemotherapy consisting of FOLFOX4 and bevacizumab. Owing to a good response to the treatment after 4 months, rectal resection was achieved curatively. Wound dehiscence occurred as a postoperative complication. The patient chose not to receive adjuvant chemotherapy. Currently, she has been alive for more than 1 year 3 months after resection without recurrence. PMID:26805353

  16. Update in Cancer Chemotherapy: Genitourinary Tract Cancer, Part 4: Testicular Cancer

    PubMed Central

    Wright, Jane C.

    1988-01-01

    An update of the state of the art of cancer chemotherapeutic treatment of genitourinary tract cancer is described in this multi-part series: included are cancers of the kidney, bladder, prostate, testicle, ovary, uterus, vulva, and gestational trophoblastic neoplasms. Part 4 is a review of treatments for cancer of the testicles. Testicular cancer is highly curable and responds well to both surgery and chemotherapy. Patients with stage I and stage II nonseminomatous germ-cell tumors may be cured by surgery alone or in combination with chemotherapy. In patients with pathologic stage II disease, the use of adjuvant chemotherapy with two courses of platinum-based combination drugs has been successful in preventing relapse. Further refinements in management and research could banish the problem of testicular cancer. PMID:3290501

  17. [ADJUVANTED INFLUENZA VACCINES: DATA FROM DIRECT COMPARATIVE STUDIES].

    PubMed

    Chernikova, M I; Vasiliev, Yu M

    2015-01-01

    Vaccines are the cornerstone of influenza control, however available vaccines are subject to certain limitations. Adjuvanted vaccines are a promising approach, however available adjuvants have a suboptimal effectiveness and safety profile. Data from direct comparative trials are necessary for selection of optimal adjuvants among currently available and search for novel safe and effective adjuvants for next generation influenza vaccines. Data from published direct comparative studies of adjuvants for influenza vaccines are summarized, a lack of such studies is noted, especially those using adequate methods and designs and comparing adjuvants of major groups (nature/source and mechanism of action). Several promising approaches of adjuvant research and development could be identified: chitosan-based adjuvants, oil-in-water emulsions and multi-component formulations (depot + immune modulating components). PMID:26829860

  18. [Chemotherapy and the heart].

    PubMed

    Plana, Juan C

    2011-05-01

    The improvements in cancer detection and therapy have created a new cohort of patients who will experience sufficient survival to develop the cardiac complications of the cancer therapy. Three-dimensional echocardiography has been validated as the ultrasound modality with the best accuracy for the calculation of ejection fraction when compared to magnetic resonance imaging, the current gold standard, making it the tool of choice, when available, for the initial evaluation and follow up of the patient receiving chemotherapy. If three-dimensional echocardiography is not available, or if the quality of the images is inadequate, the use of ultrasound contrast can be useful for the definition of the endocardial border and identification of the true apex of the heart, enhancing the ability of the interpreter to accurately calculate volumes and ejection fraction. Two-dimensional strain appears promising as a tool to identify abnormalities in myocardial mechanics very early on during cardiotoxicity, allowing the prediction of later overt systolic dysfunction. This parameter may be useful in the detection of chemotherapy treated patients who could benefit from alternate therapies, thereby decreasing the incidence of cardiotoxicity and its associated morbidity and mortality. PMID:21492985

  19. Survival Outcomes in Resected Extrahepatic Cholangiocarcinoma: Effect of Adjuvant Radiotherapy in a Surveillance, Epidemiology, and End Results Analysis

    SciTech Connect

    Vern-Gross, Tamara Z.; Shivnani, Anand T.; Chen, Ke; Lee, Christopher M.; Tward, Jonathan D.; MacDonald, O. Kenneth; Crane, Christopher H.; Talamonti, Mark S.; Munoz, Louis L.; Small, William

    2011-09-01

    Purpose: The benefit of adjuvant radiotherapy (RT) after surgical resection for extrahepatic cholangiocarcinoma has not been clearly established. We analyzed survival outcomes of patients with resected extrahepatic cholangiocarcinoma and examined the effect of adjuvant RT. Methods and Materials: Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) program between 1973 and 2003. The primary endpoint was the overall survival time. Cox regression analysis was used to perform univariate and multivariate analyses of the following clinical variables: age, year of diagnosis, histologic grade, localized (Stage T1-T2) vs. regional (Stage T3 or greater and/or node positive) stage, gender, race, and the use of adjuvant RT after surgical resection. Results: The records for 2,332 patients were obtained. Patients with previous malignancy, distant disease, incomplete or conflicting records, atypical histologic features, and those treated with preoperative/intraoperative RT were excluded. Of the remaining 1,491 patients eligible for analysis, 473 (32%) had undergone adjuvant RT. After a median follow-up of 27 months (among surviving patients), the median overall survival time for the entire cohort was 20 months. Patients with localized and regional disease had a median survival time of 33 and 18 months, respectively (p < .001). The addition of adjuvant RT was not associated with an improvement in overall or cause-specific survival for patients with local or regional disease. Conclusion: Patients with localized disease had significantly better overall survival than those with regional disease. Adjuvant RT was not associated with an improvement in long-term overall survival in patients with resected extrahepatic bile duct cancer. Key data, including margin status and the use of combined chemotherapy, was not available through the SEER database.

  20. [A CASE OF UROTHELIAL CARCINOMA OF THE URINARY BLADDER WITH SQUAMOUS DIFFERENTIATION RESPONDING TO PACLITAXEL AND CARBOPLATIN NEOADJUVANT CHEMOTHERAPY].

    PubMed

    Banno, Eri; Nishino, Aki; Nagai, Yasuharu; Yasuda, Muneo; Tahara, Hideo; Kino, Shigeo; Kanno, Norihumi

    2015-07-01

    A 42-year-old man was referred to our hospital for macrohematuria. Computer tomography and magnetic resonance imaging revealed right hydronephrosis and a retroperitoneal mass, located next to right side of the bladder. Cystoscopy showed a protruded lesion covered with normal mucosa at the right lateral wall. The patient underwent transurethral resection of the bladder tumor and biopsies of the bladder wall. Histological examination showed squamous cell carcinoma. Neoadjuvant chemotherapy using paclitaxel and carboplatin (TC) was performed. A total cystectomy, right nephroureterectomy and construction of the ileal conduit were performed after one course of systemic chemotherapy. Histological examination showed urothelial carcinoma with squamous cell differentiation. Unexpectedly, a small amount of CIS was detected only in the vicinity of the TUR scar. The patient received 2 cycles of TC chemotherapy as adjuvant chemotherapy. Unfortunately, 11 months later, local recurrence and liver metastasis were detected. He died 17 months after the surgery. PMID:26419080

  1. Pathological complete response following neoadjuvant radiotherapy and intraperitoneal perfusion chemotherapy for recurrent colon carcinoma: A case report and literature review

    PubMed Central

    BIAN, XINYU; LIU, BAORUI; YANG, YANG

    2016-01-01

    The present study reports the case of a 28-year-old male who was diagnosed with sigmoid colon carcinoma and exhibited local recurrence following radical surgery and 6 cycles of adjuvant chemotherapy. The primary surgery consisted of a partial sigmoidectomy and bladder repair. At 8 months post-chemotherapy, the patient was referred to Nanjing Drum Tower Hospital (Nanjing, China) due to local recurrence at the anastomotic site, which was confirmed by colonoscopy and total abdominal computed tomography. Synchronous intensity modulation radiation therapy and intraperitoneal (IP) perfusion chemotherapy with irinotecan (100 mg/m2) was administered. Following treatment, the object efficacy evaluation revealed a complete response and a second resection of the remaining sigmoid colon was performed. The post-operative results showed a pathological complete response. This case indicated that a combination of therapies, including radiotherapy, IP perfusion chemotherapy and surgery, may be beneficial and effective in patients with recurrent colon cancer. PMID:27073546

  2. 21 CFR 582.99 - Adjuvants for pesticide chemicals.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... § 582.99 Adjuvants for pesticide chemicals. Adjuvants, identified and used in accordance with 40 CFR 180.1001(c) and (d), which are added to pesticide use dilutions by a grower or applicator prior to... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Adjuvants for pesticide chemicals. 582.99...

  3. 21 CFR 582.99 - Adjuvants for pesticide chemicals.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... § 582.99 Adjuvants for pesticide chemicals. Adjuvants, identified and used in accordance with 40 CFR 180.1001(c) and (d), which are added to pesticide use dilutions by a grower or applicator prior to... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Adjuvants for pesticide chemicals. 582.99...

  4. 21 CFR 182.99 - Adjuvants for pesticide chemicals.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ....99 Adjuvants for pesticide chemicals. Adjuvants, identified and used in accordance with 40 CFR 180.1001 (c) and (d), which are added to pesticide use dilutions by a grower or applicator prior to... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Adjuvants for pesticide chemicals. 182.99...

  5. 21 CFR 172.710 - Adjuvants for pesticide use dilutions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Adjuvants for pesticide use dilutions. 172.710... HUMAN CONSUMPTION Other Specific Usage Additives § 172.710 Adjuvants for pesticide use dilutions. The following surfactants and related adjuvants may be safely added to pesticide use dilutions by a grower...

  6. 21 CFR 182.99 - Adjuvants for pesticide chemicals.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ....99 Adjuvants for pesticide chemicals. Adjuvants, identified and used in accordance with 40 CFR 180.910 and 40 CFR 180.920, which are added to pesticide use dilutions by a grower or applicator prior to... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Adjuvants for pesticide chemicals. 182.99...

  7. 21 CFR 582.99 - Adjuvants for pesticide chemicals.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... § 582.99 Adjuvants for pesticide chemicals. Adjuvants, identified and used in accordance with 40 CFR 180.1001(c) and (d), which are added to pesticide use dilutions by a grower or applicator prior to... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Adjuvants for pesticide chemicals. 582.99...

  8. 21 CFR 582.99 - Adjuvants for pesticide chemicals.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... § 582.99 Adjuvants for pesticide chemicals. Adjuvants, identified and used in accordance with 40 CFR 180.1001(c) and (d), which are added to pesticide use dilutions by a grower or applicator prior to... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Adjuvants for pesticide chemicals. 582.99...

  9. 21 CFR 172.710 - Adjuvants for pesticide use dilutions.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Adjuvants for pesticide use dilutions. 172.710... HUMAN CONSUMPTION Other Specific Usage Additives § 172.710 Adjuvants for pesticide use dilutions. The following surfactants and related adjuvants may be safely added to pesticide use dilutions by a grower...

  10. 21 CFR 172.710 - Adjuvants for pesticide use dilutions.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Adjuvants for pesticide use dilutions. 172.710... Additives § 172.710 Adjuvants for pesticide use dilutions. The following surfactants and related adjuvants may be safely added to pesticide use dilutions by a grower or applicant prior to application to...

  11. 21 CFR 182.99 - Adjuvants for pesticide chemicals.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ....99 Adjuvants for pesticide chemicals. Adjuvants, identified and used in accordance with 40 CFR 180.910 and 40 CFR 180.920, which are added to pesticide use dilutions by a grower or applicator prior to... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Adjuvants for pesticide chemicals. 182.99...

  12. 21 CFR 172.710 - Adjuvants for pesticide use dilutions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Adjuvants for pesticide use dilutions. 172.710... HUMAN CONSUMPTION Other Specific Usage Additives § 172.710 Adjuvants for pesticide use dilutions. The following surfactants and related adjuvants may be safely added to pesticide use dilutions by a grower...

  13. 21 CFR 182.99 - Adjuvants for pesticide chemicals.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...) SUBSTANCES GENERALLY RECOGNIZED AS SAFE General Provisions § 182.99 Adjuvants for pesticide chemicals. Adjuvants, identified and used in accordance with 40 CFR 180.910 and 40 CFR 180.920, which are added to... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Adjuvants for pesticide chemicals. 182.99...

  14. Effectiveness of spray adjuvants on reduction of spray drift

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Numerous drift reduction adjuvants and spray deposition aids are available to applicators of crop production and protection chemicals. Performance of many of the newly introduced drift control adjuvants has not been well documented for aerial application. Five new drift control adjuvants were sele...

  15. 21 CFR 172.710 - Adjuvants for pesticide use dilutions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Adjuvants for pesticide use dilutions. 172.710... HUMAN CONSUMPTION Other Specific Usage Additives § 172.710 Adjuvants for pesticide use dilutions. The following surfactants and related adjuvants may be safely added to pesticide use dilutions by a grower...

  16. 21 CFR 582.99 - Adjuvants for pesticide chemicals.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... § 582.99 Adjuvants for pesticide chemicals. Adjuvants, identified and used in accordance with 40 CFR 180.1001(c) and (d), which are added to pesticide use dilutions by a grower or applicator prior to... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Adjuvants for pesticide chemicals. 582.99...

  17. 21 CFR 182.99 - Adjuvants for pesticide chemicals.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ....99 Adjuvants for pesticide chemicals. Adjuvants, identified and used in accordance with 40 CFR 180.1001 (c) and (d), which are added to pesticide use dilutions by a grower or applicator prior to... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Adjuvants for pesticide chemicals. 182.99...

  18. Adjuvant Radiation Therapy Treatment Time Impacts Overall Survival in Gastric Cancer

    SciTech Connect

    McMillan, Matthew T.; Ojerholm, Eric; Roses, Robert E.; Plastaras, John P.; Metz, James M.; Mamtani, Ronac; Stripp, Diana; Ben-Josef, Edgar; Datta, Jashodeep

    2015-10-01

    Purpose: Prolonged radiation therapy treatment time (RTT) is associated with worse survival in several tumor types. This study investigated whether delays during adjuvant radiation therapy impact overall survival (OS) in gastric cancer. Methods and Materials: The National Cancer Data Base was queried for patients with resected gastric cancer who received adjuvant radiation therapy with National Comprehensive Cancer Network–recommended doses (45 or 50.4 Gy) between 1998 and 2006. RTT was classified as standard (45 Gy: 33-36 days, 50.4 Gy: 38-41 days) or prolonged (45 Gy: >36 days, 50.4 Gy: >41 days). Cox proportional hazards models evaluated the association between the following factors and OS: RTT, interval from surgery to radiation therapy initiation, interval from surgery to radiation therapy completion, radiation therapy dose, demographic/pathologic and operative factors, and other elements of adjuvant multimodality therapy. Results: Of 1591 patients, RTT was delayed in 732 (46%). Factors associated with prolonged RTT were non-private health insurance (OR 1.3, P=.005) and treatment at non-academic facilities (OR 1.2, P=.045). Median OS and 5-year actuarial survival were significantly worse in patients with prolonged RTT compared with standard RTT (36 vs 51 months, P=.001; 39 vs 47%, P=.005); OS worsened with each cumulative week of delay (P<.0004). On multivariable analysis, prolonged RTT was associated with inferior OS (hazard ratio 1.2, P=.002); the intervals from surgery to radiation therapy initiation or completion were not. Prolonged RTT was particularly detrimental in patients with node positivity, inadequate nodal staging (<15 nodes examined), and those undergoing a cycle of chemotherapy before chemoradiation therapy. Conclusions: Delays during adjuvant radiation therapy appear to negatively impact survival in gastric cancer. Efforts to minimize cumulative interruptions to <7 days should be considered.

  19. Potential implications of adjuvant endocrine therapy for the oral health of postmenopausal women with breast cancer

    PubMed Central

    Taichman, L. Susan; Havens, Aaron M.

    2012-01-01

    Current adjuvant treatment modalities for breast cancer that express the estrogen receptor or progesterone receptor include adjuvant anti-estrogen therapies, and tamoxifen and aromatase inhibitors. Bone, including the jaw, is an endocrine-sensitive organ, as are other oral structures. This review examines the potential links between adjuvant anti-estrogen treatments in postmenopausal women with hormone receptor positive breast cancer and oral health. A search of PubMed, EMBASE, CENTRAL, and the Web of Knowledge was conducted using combinations of key terms “breast,” “cancer,” “neoplasm,” “Tamoxifen,” “Aromatase Inhibitor,” “chemotherapy,” “hormone therapy,” “alveolar bone loss,” “postmenopausal bone loss,” “estrogen,” “SERM,” “hormone replacement therapy,” and “quality of life.” We selected articles published in peer-reviewed journals in the English. The authors found no studies reporting on periodontal diseases, alveolar bone loss, oral health, or oral health-related quality of life in association with anti-estrogen breast cancer treatments in postmenopausal women. Periodontal diseases, alveolar bone density, tooth loss, and conditions of the soft tissues of the mouth have all been associated with menopausal status supporting the hypothesis that the soft tissues and bone of the oral cavity could be negatively affected by anti-estrogen therapy. As a conclusion, the impact of adjuvant endocrine breast cancer therapy on the oral health of postmenopausal women is undefined. The structures of the oral cavity are influenced by estrogen; therefore, anti-estrogen therapies may carry the risk of oral toxicities. Oral health care for breast cancer patients is an important but understudied aspect of cancer survivorship. PMID:22986813

  20. Molecular Markers Predict Distant Metastases After Adjuvant Chemoradiation for Rectal Cancer

    SciTech Connect

    Kim, Jun Won; Kim, Yong Bae; Choi, Jun Jeong; Koom, Woong Sub; Kim, Hoguen; Kim, Nam-Kyu; Ahn, Joong Bae; Lee, Ikjae; Cho, Jae Ho; Keum, Ki Chang

    2012-12-01

    Purpose: The outcomes of adjuvant chemoradiation for locally advanced rectal cancer are nonuniform among patients with matching prognostic factors. We explored the role of molecular markers for predicting the outcome of adjuvant chemoradiation for rectal cancer patients. Methods and Materials: The study included 68 patients with stages II to III rectal adenocarcinoma who were treated with total mesorectal excision and adjuvant chemoradiation. Chemotherapy based on 5-fluorouracil and leucovorin was intravenously administered each month for 6-12 cycles. Radiation therapy consisted of 54 Gy delivered in 30 fractions. Immunostaining of surgical specimens for COX-2, EGFR, VEGF, thymidine synthase (TS), and Raf kinase inhibitor protein (RKIP) was performed. Results: The median follow-up was 65 months. Eight locoregional (11.8%) and 13 distant (19.1%) recurrences occurred. Five-year locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates for all patients were 83.9%, 78.7%, 66.7%, and 73.8%, respectively. LRFFS was not correlated with TNM stage, surgical margin, or any of the molecular markers. VEGF overexpression was significantly correlated with decreased DMFS (P=.045), while RKIP-positive results were correlated with increased DMFS (P=.025). In multivariate analyses, positive findings for COX-2 (COX-2+) and VEGF (VEGF+) and negative findings for RKIP (RKIP-) were independent prognostic factors for DMFS, DFS, and OS (P=.035, .014, and .007 for DMFS; .021, .010, and <.0001 for DFS; and .004, .012, and .001 for OS). The combination of both COX-2+ and VEGF+ (COX-2+/VEGF+) showed a strong correlation with decreased DFS (P=.007), and the combinations of RKIP+/COX-2- and RKIP+/VEGF- showed strong correlations with improved DFS compared with the rest of the patients (P=.001 and <.0001, respectively). Conclusions: Molecular markers can be valuable in predicting treatment outcome of adjuvant

  1. Adjuvant vaginal cuff brachytherapy for high-risk, early stage endometrial cancer

    PubMed Central

    Eastwick, Gary; Anne, Pramila Rani; Rosenblum, Norman G.; Schilder, Russell J.; Chalian, Raffi; Zibelli, Allison M.; Kim, Christine H.; Den, Robert

    2014-01-01

    Purpose To report outcomes following adjuvant high-dose-rate vaginal brachytherapy (VBT) with or without chemotherapy for high-intermediate risk (HIR) and high-risk, early stage endometrial cancer as defined in Gynecologic Oncology Group trial 0249. Material and methods From May 2000 to January 2014, 68 women with HIR and high-risk endometrial cancer underwent surgical staging followed by VBT. Median VBT dose was 21 Gy delivered in three fractions prescribed to 0.5 cm depth. Paclitaxel 175 mg/m2 and carboplatin area under the curve 6 was administered every 21 days in sequence with VBT. Actuarial survival estimates were calculated using the Kaplan-Meier method. Results Patient demographics included a median age of 66 years (range: 36-91) and stages IA (49%), IB (38%), and II (13%), respectively. Thirty-one (46%) patients had HIR disease with endometrioid histology, and 33 (48%) patients had serous or clear cell histology. Thirty-seven (54%) patients received a median 3 cycles (range: 3-6) of chemotherapy in addition to VBT, and 65 patients (96%) completed all prescribed therapy. During a median follow up of 33.1 months (range: 4.0-161.7), four patients have recurred, including one vaginal recurrence. The 3-year estimates of vaginal, pelvic, and distant recurrences were 1.9%, 2.4%, and 9.1%, respectively. The 3-year rates of disease-free and overall survival were 87.7% and 93.9%, respectively. Conclusions Early outcomes with adjuvant VBT with or without chemotherapy demonstrate high rates of vaginal and pelvic control for women with HIR disease. Early vaginal and pelvic relapses in high-risk patients suggest that pelvic external beam radiotherapy is warranted in this subgroup, but additional data from large phase III trials is warranted. PMID:25337127

  2. A phase III randomized study on the sequencing of radiotherapy and chemotherapy in the conservative management of early-stage breast cancer

    SciTech Connect

    Arcangeli, Giorgio . E-mail: arcangeli@ifo.it; Pinnaro, Paola; Rambone, Rita; Giannarelli, Diana; Benassi, Marcello

    2006-01-01

    Purpose: To compare two different timings of radiation treatment in patients with breast cancer who underwent conservative surgery and were candidates to receive adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy. Methods and Materials: A total of 206 patients who had quadrantectomy and axillary dissection for breast cancer and were planned to receive adjuvant CMF chemotherapy were randomized to concurrent or sequential radiotherapy. Radiotherapy was delivered only to the whole breast through tangential fields to a dose of 50 Gy in 20 fractions over 4 weeks, followed by an electron boost of 10-15 Gy in 4-6 fractions to the tumor bed. Results: No differences in 5-year breast recurrence-free, metastasis-free, disease-free, and overall survival were observed in the two treatment groups. All patients completed the planned radiotherapy. No evidence of an increased risk of toxicity was observed between the two arms. No difference in radiotherapy and in the chemotherapy dose intensity was observed in the two groups. Conclusions: In patients with negative surgical margins receiving adjuvant chemotherapy, radiotherapy can be delayed to up to 7 months. Concurrent administration of CMF chemotherapy and radiotherapy is safe and might be reserved for patients at high risk of local recurrence, such as those with positive surgical margins or larger tumor diameters.

  3. Evaluation of monophosphoryl lipid A as an immune adjuvant for photodynamic therapy in a rat sarcoma model: preliminary results

    NASA Astrophysics Data System (ADS)

    Lucroy, Michael D.; Edwards, Benjamin F.; Griffey, Stephen M.; Madewell, Bruce R.

    1999-06-01

    Photodynamic therapy (PDT) is a treatment option for several forms of human cancer, and like traditional chemotherapy and ionizing radiation therapy, PDT alone is not curative for some cases. Recent efforts have aimed at developing strategies for adjuvant therapy for PDT. Given the nature of PDT-mediated cell damage, immunotherapy is a promising adjuvant for long-term control of solid tumors. A candidate immune stimulant for use with PDT is monophosphoryl lipid A (MLA), a non-toxic fraction of the endotoxin molecule. The hypothesis is that adjuvant MLA immunotherapy with PDT will improve local tumor control and prevent growth of subsequently implanted tumor cells when compared to PDT alone. To date, no significant differences in circulating leukocyte populations or tumor infiltrating lymphocyte populations have been identified in 9L tumor-bearing F344 rats after systemic administrations of MLA. Likewise, no significant difference has been identified in local tumor control following PDT of 9L tumors with or without adjuvant MLA. Further results are pending.

  4. Chemotherapy targeting cancer stem cells

    PubMed Central

    Liu, Haiguang; Lv, Lin; Yang, Kai

    2015-01-01

    Conventional chemotherapy is the main treatment for cancer and benefits patients in the form of decreased relapse and metastasis and longer overall survival. However, as the target therapy drugs and delivery systems are not wholly precise, it also results in quite a few side effects, and is less efficient in many cancers due to the spared cancer stem cells, which are considered the reason for chemotherapy resistance, relapse, and metastasis. Conventional chemotherapy limitations and the cancer stem cell hypothesis inspired our search for a novel chemotherapy targeting cancer stem cells. In this review, we summarize cancer stem cell enrichment methods, the search for new efficient drugs, and the delivery of drugs targeting cancer stem cells. We also discuss cancer stem cell hierarchy complexity and the corresponding combination therapy for both cancer stem and non-stem cells. Learning from cancer stem cells may reveal novel strategies for chemotherapy in the future. PMID:26045975

  5. Impact of Adjuvant Therapy on Survival in Curatively Resected Gallbladder Carcinoma

    PubMed Central

    Asthana, Anupam Kumar

    2015-01-01

    Background Gallbladder carcinoma (GBC) has the propensity to fail at loco-regional (LR) and distant sites despite aggressive radical surgery. Adjuvant therapy in the form of radiotherapy (RT), systemic chemotherapy (CT) and chemoradiation (CRT) is the usual practice. Due to rarity of this disease, there is limited evidence to suggest the type of adjuvant treatment which should be offered to the patients. Aim The study was conducted to evaluate the impact of adjuvant treatment on curatively resected GBC patients. Settings and Design Histological proven patients of GBC registered between June, 2008 and July, 2014 were identified from our hospital database and retrospective analysis was done. Materials and Methods Patients of GBC who had curative resection followed by adjuvant treatment as RT alone, CT alone or CRT were included in the study. Statistical Analysis Adverse prognostic factors and the effect of adjuvant treatment on overall survival (OS) and disease free survival (DFS) were evaluated using Cox Regression Method and Kaplan Meier plot. Results We identified 33 patients of which 23 were Stage I or II disease (Early disease) and the remaining 10 were Stage III or IV disease (Advanced disease). All except one patient had adenocarcinoma. A total of 5 patients were treated with RT alone while 16 patients received CT alone. The remaining 12 patients were treated with CRT. Median follow-up period was 8.5 months. At analysis 4 were alive while the remaining 29 were dead due to disease. With regard to “Early disease” patients who had RT alone, CT alone and CRT, the median OS was 22.3, 10.3 and 15.2 months respectively (p = .440). Cohort of patients with “Advanced disease” who were treated with CT alone and CRT the median OS was 7.5 and 7.0 months respectively (p = .643). On multivariate analysis none of the prognostic factors had an adverse impact on survival. Conclusion The impact of adjuvant treatment in the form of RT, CT or CRT after curative resection

  6. Induction of lupus autoantibodies by adjuvants

    USGS Publications Warehouse

    Satoh, M.; Kuroda, Y.; Yoshida, H.; Behney, K.M.; Mizutani, A.; Akaogi, J.; Nacionales, D.C.; Lorenson, T.D.; Rosenbauer, R.J.; Reeves, W.H.

    2003-01-01

    Exposure to the hydrocarbon oil pristane induces lupus specific autoantibodies in non-autoimmune mice. We investigated whether the capacity to induce lupus-like autoimmunity is a unique property of pristane or is shared by other adjuvant oils. Seven groups of 3-month-old female BALB/cJ mice received a single intraperitoneal injection of pristane, squalene (used in the adjuvant MF59), incomplete Freund's adjuvant (IFA), three different medicinal mineral oils, or saline, respectively. Serum autoantibodies and peritoneal cytokine production were measured. In addition to pristane, the mineral oil Bayol F (IFA) and the endogenous hydrocarbon squalene both induced anti-nRNP/Sm and -Su autoantibodies (20% and 25% of mice, respectively). All of these hydrocarbons had prolonged effects on cytokine production by peritoneal APCs. However, high levels of IL-6, IL-12, and TNF?? production 2-3 months after intraperitoneal injection appeared to be associated with the ability to induce lupus autoantibodies. The ability to induce lupus autoantibodies is shared by several hydrocarbons and is not unique to pristane. It correlates with stimulation of the production of IL-12 and other cytokines, suggesting a relationship with a hydrocarbon's adjuvanticity. The potential to induce autoimmunity may complicate the use of oil adjuvants in human and veterinary vaccines. ?? 2003 Elsevier Ltd. All rights reserved.

  7. Adjuvant and Definitive Radiotherapy for Adrenocortical Carcinoma

    SciTech Connect

    Sabolch, Aaron; Feng, Mary; Griffith, Kent; Hammer, Gary; Doherty, Gerard; Ben-Josef, Edgar

    2011-08-01

    Purpose: To evaluate the impact of both adjuvant and definitive radiotherapy on local control of adrenocortical carcinoma. Methods and Materials: Outcomes were analyzed from 58 patients with 64 instances of treatment for adrenocortical carcinoma at the University of Michigan's Multidisciplinary Adrenal Cancer Clinic. Thirty-seven of these instances were for primary disease, whereas the remaining 27 were for recurrent disease. Thirty-eight of the treatment regimens involved surgery alone, 10 surgery plus adjuvant radiotherapy, and 16 definitive radiotherapy for unresectable disease. The effects of patient, tumor, and treatment factors were modeled simultaneously using multiple variable Cox proportional hazards regression for associations with local recurrence, distant recurrence, and overall survival. Results: Local failure occurred in 16 of the 38 instances that involved surgery alone, in 2 of the 10 that consisted of surgery plus adjuvant radiotherapy, and in 1 instance of definitive radiotherapy. Lack of radiotherapy use was associated with 4.7 times the risk of local failure compared with treatment regimens that involved radiotherapy (95% confidence interval, 1.2-19.0; p = 0.030). Conclusions: Radiotherapy seems to significantly lower the risk of local recurrence/progression in patients with adrenocortical carcinoma. Adjuvant radiotherapy should be strongly considered after surgical resection.

  8. Adjuvant steroids and relapse of typhoid fever.

    PubMed

    Cooles, P

    1986-10-01

    In a retrospective study, relapse after non-severe acute typhoid fever was highly significantly related to the use of adjuvant steroid in the initial illness. The steroid was given late and in small doses when compared with other studies. Caution should be observed when using steroids in this way as relapse though often mild may be a severe illness. PMID:3795323

  9. Aluminum vaccine adjuvants: are they safe?

    PubMed

    Tomljenovic, L; Shaw, C A

    2011-01-01

    Aluminum is an experimentally demonstrated neurotoxin and the most commonly used vaccine adjuvant. Despite almost 90 years of widespread use of aluminum adjuvants, medical science's understanding about their mechanisms of action is still remarkably poor. There is also a concerning scarcity of data on toxicology and pharmacokinetics of these compounds. In spite of this, the notion that aluminum in vaccines is safe appears to be widely accepted. Experimental research, however, clearly shows that aluminum adjuvants have a potential to induce serious immunological disorders in humans. In particular, aluminum in adjuvant form carries a risk for autoimmunity, long-term brain inflammation and associated neurological complications and may thus have profound and widespread adverse health consequences. In our opinion, the possibility that vaccine benefits may have been overrated and the risk of potential adverse effects underestimated, has not been rigorously evaluated in the medical and scientific community. We hope that the present paper will provide a framework for a much needed and long overdue assessment of this highly contentious medical issue. PMID:21568886

  10. Redefining Adjuvant Therapy for Colon Cancer

    Cancer.gov

    In this trial, patients with resected stage III colon cancer are being randomly assigned to receive FOLFOX chemotherapy for either 3 or 6 months and to take either a pill called celecoxib or a matching placebo pill for 3 years.

  11. Fam65b is important for formation of the HDAC6-dysferlin protein complex during myogenic cell differentiation.

    PubMed

    Balasubramanian, Anuradha; Kawahara, Genri; Gupta, Vandana A; Rozkalne, Anete; Beauvais, Ariane; Kunkel, Louis M; Gussoni, Emanuela

    2014-07-01

    Previously, we identified family with sequence similarity 65, member B (Fam65b), as a protein transiently up-regulated during differentiation and fusion of human myogenic cells. Silencing of Fam65b expression results in severe reduction of myogenin expression and consequent lack of myoblast fusion. The molecular function of Fam65b and whether misregulation of its expression could be causative of muscle diseases are unknown. Protein pulldowns were used to identify Fam65b-interacting proteins in differentiating human muscle cells and regenerating muscle tissue. In vitro, human muscle cells were treated with histone-deacetylase (HDAC) inhibitors, and expression of Fam65b and interacting proteins was studied. Nontreated cells were used as controls. In vivo, expression of Fam65b was down-regulated in developing zebrafish to determine the effects on muscle development. Fam65b binds to HDAC6 and dysferlin, the protein mutated in limb girdle muscular dystrophy 2B. The tricomplex Fam65b-HDAC6-dysferlin is transient, and Fam65b expression is necessary for the complex to form. Treatment of myogenic cells with pan-HDAC or HDAC6-specific inhibitors alters Fam65b expression, while dysferlin expression does not change. Inhibition of Fam65b expression in developing zebrafish results in abnormal muscle, with low birefringence, tears at the myosepta, and increased embryo lethality. Fam65b is an essential component of the HDAC6-dysferlin complex. Down-regulation of Fam65b in developing muscle causes changes consistent with muscle disease.-Balasubramanian, A., Kawahara, G., Gupta, V. A., Rozkalne, A., Beauvais, A., Kunkel, L. M., Gussoni, E. Fam65b is important for formation of the HDAC6-dysferlin protein complex during myogenic cell differentiation. PMID:24687993

  12. Methylation status at HYAL2 predicts overall and progression-free survival of colon cancer patients under 5-FU chemotherapy.

    PubMed

    Pfütze, Katrin; Benner, Axel; Hoffmeister, Michael; Jansen, Lina; Yang, Rongxi; Bläker, Hendrik; Herpel, Esther; Ulrich, Alexis; Ulrich, Cornelia M; Chang-Claude, Jenny; Brenner, Hermann; Burwinkel, Barbara

    2015-12-01

    DNA methylation variations in gene promoter regions are well documented tumor-specific alterations in human malignancies including colon cancer, which may influence tumor behavior and clinical outcome. As a subset of colon cancer patients does not benefit from adjuvant chemotherapy, predictive biomarkers are desirable. Here, we describe that DNA methylation levels at CpG loci of hyaluronoglucosaminidase 2 (HYLA2) could be used to identify stage II and III colon cancer patients who are most likely to benefit from 5-flourouracil (5-FU) chemotherapy with respect to overall survival and progression-free survival. PMID:26453961

  13. Pioneers in Antimicrobial Chemotherapy.

    PubMed

    Gupta, Neha; Rodrigues, Camilla; Soman, Rajeev

    2015-09-01

    "If we are not careful, we soon will be in the post-antibiotic era, and for some patients and some microbes we are already there"- Tom Friedan Antibiotics revolutionized medicine in the 20th century. The era of antibacterial chemotherapy began in 1907 with the discovery of arsphenamine, first synthesized by Alferd Bertheim and Paul Ehrlich in 1907, used to treat syphilis. The first systemically active antibiotic, Prontosil was discovered in 1933 by Gerhard Domagk, for which he was awarded the 1939 Nobel Prize. Fleming's accidental discovery and isolation of penicillin in September 1928 marked the start of modern antibiotics. It was a discovery that changed the course of history and saved millions of lives. PMID:27608881

  14. Vitamins as influenza vaccine adjuvant components.

    PubMed

    Quintilio, Wagner; de Freitas, Fábio Alessandro; Rodriguez, Dunia; Kubrusly, Flavia Saldanha; Yourtov, Dimitri; Miyaki, Cosue; de Cerqueira Leite, Luciana Cezar; Raw, Isaias

    2016-10-01

    A number of adjuvant formulations were assayed in mice immunized with 3.75 µg of A/California/7/2009 (H1N1) pdm09 influenza vaccine with vitamins A, D and/or E in emulsions or B2 and/or B9 combined with Bordetella pertussis MPLA and/or alum as adjuvants. Squalene was used as positive control, as well as MPLA with alum. The immune response was evaluated by a panel of tests, including a hemagglutination inhibition (HAI) test, ELISA for IgG, IgG1, and IgG2a and IFN-γ, IL-2, IL-6 and IL-10 quantification in splenocyte culture supernatant after stimulus with influenza antigen. Immunological memory was evaluated using a 1/10 dose booster 60 days after the first immunization followed by assessment of the response by HAI, IgG ELISA, and determination of the antibody affinity index. The highest increases in HAI, IgG1 and IgG2a titers were obtained with the adjuvant combinations containing vitamin E, or the hydrophilic combinations containing MPLA and alum or B2 and alum. The IgG1/IgG2a ratio indicates that the response to the combination of B2 with alum would have more Th2 character than the combination of MPLA with alum. In an assay to investigate the memory response, a significant increase in HAI titer was observed with a booster vaccine dose at 60 days after immunization with vaccines containing MPLA with alum or B2 with alum. Overall, of the 27 adjuvant combinations, MPLA with alum and B2 with alum were the most promising adjuvants to be evaluated in humans. PMID:27449155

  15. A rehabilitation program for lung cancer patients during postthoracotomy chemotherapy

    PubMed Central

    Hoffman, Amy J; Brintnall, Ruth Ann; von Eye, Alexander; Jones, Lee W; Alderink, Gordon; Patzelt, Lawrence H; Brown, Jean K

    2014-01-01

    Objective The objective of this pilot study was to describe the effects of a 16-week home-based rehabilitative exercise program on cancer-related fatigue (CRF), other symptoms, functional status, and quality of life (QOL) for patients with non-small cell lung cancer (NSCLC) after thoracotomy starting within days after hospital discharge and continuing through the initiation and completion of chemotherapy. Materials and methods Five patients with NSCLC completed the Brief Fatigue Inventory (measuring CRF severity) and the MD Anderson Symptom Inventory (measuring symptom severity) before and after thoractomy, and at the end of each week of the 16-week exercise program. Additionally, the Medical Outcomes Study Short Form-36 (measuring physical and mental functional status) and the Quality of Life Index (measuring QOL) were completed before and after thoracotomy, after weeks 3, 6, 12, and 16 (the end of the exercise program). Further, the 6-minute walk test (measuring functional capacity) was administered before thoracotomy, prior to the initiation of chemotherapy and/or radiation therapy, and at the end of the 16-week exercise program, after completion of chemotherapy. Results Participants had a mean age of 63 years and a mean of five comorbid conditions; the exercise program was initiated within 4 days after hospital discharge. Participants’ CRF severity scores were reduced to mild levels, while the mean number of symptoms decreased from 9 postthoracotomy to 6 after the exercise program, with mean levels of severity and interference decreasing to below prethoracotomy levels. Likewise, participants’ functional status and QOL after completing the exercise program improved to near or above prethoracotomy levels. Conclusion The home-based, light-intensity exercise program for NSCLC patients receiving and completing adjuvant chemotherapy postthoracotomy showed promising trends in improving CRF severity, other symptom severity, functional status, and QOL. Further

  16. Adjuvant Chemotherapy for Brain Tumors Delivered via a Novel Intra-Cavity Moldable Polymer Matrix

    PubMed Central

    Rahman, Cheryl V.; Smith, Stuart J.; Morgan, Paul S.; Langmack, Keith A.; Clarke, Phil A.; Ritchie, Alison A.; Macarthur, Donald C.; Rose, Felicity R.; Shakesheff, Kevin M.; Grundy, Richard G.; Ruman Rahman

    2013-01-01

    Introduction Polymer-based delivery systems offer innovative intra-cavity administration of drugs, with the potential to better target micro-deposits of cancer cells in brain parenchyma beyond the resected cavity. Here we evaluate clinical utility, toxicity and sustained drug release capability of a novel formulation of poly(lactic-co-glycolic acid) (PLGA)/poly(ethylene glycol) (PEG) microparticles. Methods PLGA/PEG microparticle-based matrices were molded around an ex vivo brain pseudo-resection cavity and analyzed using magnetic resonance imaging and computerized tomography. In vitro toxicity of the polymer was assessed using tumor and endothelial cells and drug release from trichostatin A-, etoposide- and methotrexate-loaded matrices was determined. To verify activity of released agents, tumor cells were seeded onto drug-loaded matrices and viability assessed. Results PLGA/PEG matrices can be molded around a pseudo-resection cavity wall with no polymer-related artifact on clinical scans. The polymer withstands fractionated radiotherapy, with no disruption of microparticle structure. No toxicity was evident when tumor or endothelial cells were grown on control matrices in vitro. Trichostatin A, etoposide and methotrexate were released from the matrices over a 3-4 week period in vitro and etoposide released over 3 days in vivo, with released agents retaining cytotoxic capabilities. PLGA/PEG microparticle-based matrices molded around a resection cavity wall are distinguishable in clinical scanning modalities. Matrices are non-toxic in vitro suggesting good biocompatibility in vivo. Active trichostatin A, etoposide and methotrexate can be incorporated and released gradually from matrices, with radiotherapy unlikely to interfere with release. Conclusion The PLGA/PEG delivery system offers an innovative intra-cavity approach to administer chemotherapeutics for improved local control of malignant brain tumors. PMID:24155955

  17. Trial Watch: Immunogenic cell death inducers for anticancer chemotherapy

    PubMed Central

    Pol, Jonathan; Vacchelli, Erika; Aranda, Fernando; Castoldi, Francesca; Eggermont, Alexander; Cremer, Isabelle; Sautès-Fridman, Catherine; Fucikova, Jitka; Galon, Jérôme; Spisek, Radek; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2015-01-01

    The term “immunogenic cell death” (ICD) is now employed to indicate a functionally peculiar form of apoptosis that is sufficient for immunocompetent hosts to mount an adaptive immune response against dead cell-associated antigens. Several drugs have been ascribed with the ability to provoke ICD when employed as standalone therapeutic interventions. These include various chemotherapeutics routinely employed in the clinic (e.g., doxorubicin, epirubicin, idarubicin, mitoxantrone, bleomycin, bortezomib, cyclophosphamide and oxaliplatin) as well as some anticancer agents that are still under preclinical or clinical development (e.g., some microtubular inhibitors of the epothilone family). In addition, a few drugs are able to convert otherwise non-immunogenic instances of cell death into bona fide ICD, and may therefore be employed as chemotherapeutic adjuvants within combinatorial regimens. This is the case of cardiac glycosides, like digoxin and digitoxin, and zoledronic acid. Here, we discuss recent developments on anticancer chemotherapy based on ICD inducers. PMID:26137404

  18. New generation adjuvants--from empiricism to rational design.

    PubMed

    O'Hagan, Derek T; Fox, Christopher B

    2015-06-01

    Adjuvants are an essential component of modern vaccine development. Despite many decades of development, only a few types of adjuvants are currently included in vaccines approved for human use. In order to better understand the reasons that development of some adjuvants succeeded while many others failed, we discuss some of the common attributes of successful first generation adjuvants. Next, we evaluate current trends in the development of second generation adjuvants, including the potential advantages of rationally designed synthetic immune potentiators appropriately formulated. Finally, we discuss desirable attributes of next generation adjuvants. Throughout, we emphasize that the importance of formulation and analytical characterization in all aspects of vaccine adjuvant development is often underappreciated. We highlight the formulation factors that must be evaluated in order to optimize interactions between vaccine antigens, immune potentiators, and particulate formulations, and the resulting effects on safety, biological activity, manufacturability, and stability. PMID:26022561

  19. Postoperative Chemoradiotherapy Combined with Epirubicin-Based Triplet Chemotherapy for Locally Advanced Adenocarcinoma of the Stomach or Gastroesophageal Junction

    PubMed Central

    Li, Guichao; Zhang, Zhen; Ma, Xuejun; Zhu, Ji; Cai, Gang

    2013-01-01

    Background Due to low tolerance to chemotherapy, the maximum number of cycles of postoperative adjuvant chemotherapy is 4 in adjuvant gastric clinical trials. The aim of this study is to retrospectively evaluate the safety and efficacy of adjuvant epirubicin-based triplet chemotherapy and radiotherapy in the treatment of resected locally advanced stomach or gastroesophageal junction adenocarcinoma. Methodology/Principal Findings From January 2004 to July 2008, ninety-seven consecutive gastric or gastroesophageal junction adenocarcinoma patients in stages T3–4/N+ were treated with postoperative radiotherapy and chemotherapy. The recommended treatment plan was radical resection followed by 1–2 cycles of adjuvant chemotherapy (ACT), postoperative chemoradiotherapy (CRT), and, finally, 4–5 cycles of ACT. The patients were classified into two groups depending on the number of cycles of ACT: group 1 received 4–6 cycles (n = 59), and group 2 received 0–3 cycles (n = 38). The detailed grouping is as follows: RT alone, 2; RT and CT, 18; concurrent RTCT and CT, 41; and CRT, 36. Of the 97 patients, 77 patients received concurrent therapy (CRT, (5-fluorouracil or capecitabine), and 20 received radiotherapy alone because of patient refusal (n = 15) or treatment toxicity (n = 5). After a median follow-up of 44 months, the 3-year disease free survival(DFS) and overall survival (OS) were 66.5% and 69.5% for group 1 and 45.5% and 50% for group 2, respectively (p = 0.005 and p = 0.024). Multivariate analysis revealed that 4–6 cycles of ACT, lymphovascular invasion, or peritoneal metastasis were independent prognostic factors for disease-free survival or overall survival (p<0.05). Conclusions/Significance This study demonstrates that concurrent chemoradiation with adjuvant epirubicin-based triplet chemotherapy is feasible and tolerable for gastric or gastroesophageal junction carcinoma patients. Patients can benefit from more cycles of ACT. PMID

  20. A photometric analysis of free alveolar macrophages (FAMs) in smoking and nonsmoking firefighters.

    PubMed

    Mehm, W J; Giesecke, G F

    1986-10-01

    The effects of cigarette smoking and chronic smoke inhalation were evaluated in free alveolar macrophages (FAMs) in firefighters and police officers from the city of Denver, CO. Evaluation was accomplished by comparing statistical morphometric and photometric data taken from digital images of FAMs generated by the microscope photometer. Although our results failed to show significant differences between occupations and smoking status in FAM size, degree of size variability, or nuclear/cytoplasmic area ratios, they did demonstrate a significant difference in the degree of nuclear and cytoplasmic optical density (O.D.) between both occupation and smoking status. Firefighters consistently showed significantly greater O.D. values than police officers while smokers demonstrated a significantly greater O.D. than nonsmokers. While the meaning of these findings remains illusive, they do, however, present quantitative data supporting the biological response of the FAM to occupational and cigarette smoke inhalation. PMID:3022703

  1. Identification of FAM96B as a novel prelamin A binding partner.

    PubMed

    Xiong, Xing-Dong; Wang, Junwen; Zheng, Huiling; Jing, Xia; Liu, Zhenjie; Zhou, Zhongjun; Liu, Xinguang

    2013-10-11

    Prelamin A accumulation causes nuclear abnormalities, impairs nuclear functions, and eventually promotes cellular senescence. However, the underlying mechanism of how prelamin A promotes cellular senescence is still poorly understood. Here we carried out a yeast two-hybrid screen using a human skeletal muscle cDNA library to search for prelamin A binding partners, and identified FAM96B as a prelamin A binding partner. The interaction of FAM96B with prelamin A was confirmed by GST pull-down and co-immunoprecipitation experiments. Furthermore, co-localization experiments by fluorescent confocal microscopy revealed that FAM96B colocalized with prelamin A in HEK-293 cells. Taken together, our data demonstrated the physical interaction between FAM96B and prelamin A, which may provide some clues to the mechanisms of prelamin A in premature aging. PMID:24041693

  2. FAM83D activates the MEK/ERK signaling pathway and promotes cell proliferation in hepatocellular carcinoma

    SciTech Connect

    Wang, Dong; Han, Sheng; Peng, Rui; Wang, Xing; Yang, Xin-Xiang; Yang, Ren-Jie; Jiao, Chen-Yu; Ding, Dong; Ji, Gu-Wei; Li, Xiang-Cheng

    2015-03-06

    Publicly available microarray data suggests that the expression of FAM83D (Family with sequence similarity 83, member D) is elevated in a wide variety of tumor types, including hepatocellular carcinoma (HCC). However, its role in the pathogenesis of HCC has not been elucidated. Here, we showed that FAM83D was frequently up-regulated in HCC samples. Forced FAM83D expression in HCC cell lines significantly promoted their proliferation and colony formation while FAM83D knockdown resulted in the opposite effects. Mechanistic analyses indicated that FAM83D was able to activate the MEK/ERK signaling pathway and promote the entry into S phase of cell cycle progression. Taken together, these results demonstrate that FAM83D is a novel oncogene in HCC development and may constitute a potential therapeutic target in HCC. - Highlights: • FAM83D is up-regulated in HCC tissues and cell lines. • Ectopic expression of FAM83D promotes HCC cell proliferation and colony formation. • Depletion of FAM83D inhibits HCC cell proliferation and colony formation. • FAM83D activates the MEK/ERK signaling pathway in HCC.

  3. Characterization of Fam20C expression in odontogenesis and osteogenesis using transgenic mice

    PubMed Central

    Du, Er-Xia; Wang, Xiao-Fang; Yang, Wu-Chen; Kaback, Deborah; Yee, Siu-Pok; Qin, Chun-Lin; George, Anne; Hao, Jian-Jun

    2015-01-01

    Our previous studies have demonstrated that Fam20C promotes differentiation and mineralization of odontoblasts, ameloblasts, osteoblasts and osteocytes during tooth and bone development. Ablation of the Fam20C gene inhibits bone and tooth growth by increasing fibroblast growth factor 23 in serum and causing hypophosphatemia in conditional knockout mice. However, control and regulation of the expression of Fam20C are still unknown. In this study, we generated a transgenic reporter model which expresses green fluorescence protein (GFP) driven by the Fam20C promoter. Recombineering was used to insert a 16 kb fragment of the mouse Fam20C gene (containing the 15 kb promoter and 1.1 kb of exon 1) into a pBluescript SK vector with the topaz variant of GFP and a bovine growth hormone polyadenylation sequence. GFP expression was subsequently evaluated by histomorphometry on cryosections from E14 to adult mice. Fluorescence was evident in the bone and teeth as early as E17.5. The GFP signal was maintained stably in odontoblasts and osteoblasts until 4 weeks after birth. The expression of GFP was significantly reduced in teeth, alveolar bone and muscle by 8 weeks of age. We also observed colocalization of the GFP signal with the Fam20C antibody in postnatal 1- and 7-day-old animals. Successful generation of Fam20C-GFP transgenic mice will provide a unique model for studying Fam20C gene expression and the biological function of this gene during odontogenesis and osteogenesis. PMID:25537657

  4. Characterization of Fam20C expression in odontogenesis and osteogenesis using transgenic mice.

    PubMed

    Du, Er-Xia; Wang, Xiao-Fang; Yang, Wu-Chen; Kaback, Deborah; Yee, Siu-Pok; Qin, Chun-Lin; George, Anne; Hao, Jian-Jun

    2015-06-01

    Our previous studies have demonstrated that Fam20C promotes differentiation and mineralization of odontoblasts, ameloblasts, osteoblasts and osteocytes during tooth and bone development. Ablation of the Fam20C gene inhibits bone and tooth growth by increasing fibroblast growth factor 23 in serum and causing hypophosphatemia in conditional knockout mice. However, control and regulation of the expression of Fam20C are still unknown. In this study, we generated a transgenic reporter model which expresses green fluorescence protein (GFP) driven by the Fam20C promoter. Recombineering was used to insert a 16 kb fragment of the mouse Fam20C gene (containing the 15 kb promoter and 1.1 kb of exon 1) into a pBluescript SK vector with the topaz variant of GFP and a bovine growth hormone polyadenylation sequence. GFP expression was subsequently evaluated by histomorphometry on cryosections from E14 to adult mice. Fluorescence was evident in the bone and teeth as early as E17.5. The GFP signal was maintained stably in odontoblasts and osteoblasts until 4 weeks after birth. The expression of GFP was significantly reduced in teeth, alveolar bone and muscle by 8 weeks of age. We also observed colocalization of the GFP signal with the Fam20C antibody in postnatal 1- and 7-day-old animals. Successful generation of Fam20C-GFP transgenic mice will provide a unique model for studying Fam20C gene expression and the biological function of this gene during odontogenesis and osteogenesis. PMID:25537657

  5. Pancreatic Neuroendocrine Tumors With Involved Surgical Margins: Prognostic Factors and the Role of Adjuvant Radiotherapy

    SciTech Connect

    Arvold, Nils D.; Willett, Christopher G.; Fernandez-del Castillo, Carlos; Ryan, David P.; Ferrone, Cristina R.; Clark, Jeffrey W.; Blaszkowsky, Lawrence S.; Deshpande, Vikram; Niemierko, Andrzej; Allen, Jill N.; Kwak, Eunice L.; Wadlow, Raymond C.; Zhu, Andrew X.; Warshaw, Andrew L.; Hong, Theodore S.

    2012-07-01

    Purpose: Pancreatic neuroendocrine tumors (pNET) are rare neoplasms associated with poor outcomes without resection, and involved surgical margins are associated with a worse prognosis. The role of adjuvant radiotherapy (RT) in these patients has not been characterized. Methods and Materials: We retrospectively evaluated 46 consecutive patients with positive or close (<1 mm) margins after pNET resection, treated from 1983 to 2010, 16 of whom received adjuvant RT. Median RT dose was 50.4 Gy in 1.8-Gy fractions; half the patients received concurrent chemotherapy with 5-fluorouracil or capecitabine. No patients received adjuvant chemotherapy. Cox multivariate analysis (MVA) was used to analyze factors associated with overall survival (OS). Results: Median age at diagnosis was 56 years, and 52% of patients were female. Median tumor size was 38 mm, 57% of patients were node-positive, and 11% had a resected solitary liver metastasis. Patients who received RT were more likely to have larger tumors (median, 54 mm vs. 30 mm, respectively, p = 0.002) and node positivity (81% vs. 33%, respectively, p = 0.002) than those not receiving RT. Median follow-up was 39 months. Actuarial 5-year OS was 62% (95% confidence interval [CI], 41%-77%). In the group that did not receive RT, 3 patients (10%) experienced local recurrence (LR) and 5 patients (18%) developed new distant metastases, while in the RT group, 1 patient (6%) experienced LR and 5 patients (38%) developed distant metastases. Of all recurrences, 29% were LR. On MVA, male gender (adjusted hazard ratio [AHR] = 3.81; 95% CI, 1.21-11.92; p = 0.02) and increasing tumor size (AHR = 1.02; 95% CI, 1.01-1.04; p = 0.007) were associated with decreased OS. Conclusions: Long-term survival is common among patients with involved-margin pNET. Despite significantly worse pathologic features among patients receiving adjuvant RT, rates of LR between groups were similar, suggesting that RT might aid local control, and merits further

  6. Treatment of Oral Cavity Squamous Cell Carcinoma With Adjuvant or Definitive Intensity-Modulated Radiation Therapy

    SciTech Connect

    Sher, David J.; Thotakura, Vijaya; Balboni, Tracy A.; Norris, Charles M.; Haddad, Robert I.; Posner, Marshall R.; Lorch, Jochen; Goguen, Laura A.; Annino, Donald J.; Tishler, Roy B.

    2011-11-15

    Purpose: The optimal management of oral cavity squamous cell carcinoma (OCSCC) typically involves surgical resection followed by adjuvant radiotherapy or chemoradiotherapy (CRT) in the setting of adverse pathologic features. Intensity-modulated radiation therapy (IMRT) is frequently used to treat oral cavity cancers, but published IMRT outcomes specific to this disease site are sparse. We report the Dana-Farber Cancer Institute experience with IMRT-based treatment for OCSCC. Methods and Materials: Retrospective study of all patients treated at Dana-Farber Cancer Institute for OCSCC with adjuvant or definitive IMRT between August 2004 and December 2009. The American Joint Committee on Cancer disease stage criteria distribution of this cohort included 5 patients (12%) with stage I; 10 patients (24%) with stage II (n = 10, 24%),; 14 patients (33%) with stage III (n = 14, 33%),; and 13 patients (31%) with stage IV. The primary endpoint was overall survival (OS); secondary endpoints were locoregional control (LRC) and acute and chronic toxicity. Results: Forty-two patients with OCSCC were included, 30 of whom were initially treated with surgical resection. Twenty-three (77%) of 30 surgical patients treated with adjuvant IMRT also received concurrent chemotherapy, and 9 of 12 (75%) patients treated definitively without surgery were treated with CRT or induction chemotherapy and CRT. With a median follow-up of 2.1 years (interquartile range, 1.1-3.1 years) for all patients, the 2-year actuarial rates of OS and LRC following adjuvant IMRT were 85% and 91%, respectively, and the comparable results for definitive IMRT were 63% and 64% for OS and LRC, respectively. Only 1 patient developed symptomatic osteoradionecrosis, and among patients without evidence of disease, 35% experienced grade 2 to 3 late dysphagia, with only 1 patient who was continuously gastrostomy-dependent. Conclusions: In this single-institution series, postoperative IMRT was associated with promising LRC

  7. FAM222B Is Not a Likely Novel Candidate Gene for Cerebral Cavernous Malformations.

    PubMed

    Spiegler, Stefanie; Kirchmaier, Bettina; Rath, Matthias; Korenke, G Christoph; Tetzlaff, Fabian; van de Vorst, Maartje; Neveling, Kornelia; Acker-Palmer, Amparo; Kuss, Andreas W; Gilissen, Christian; Fischer, Andreas; Schulte-Merker, Stefan; Felbor, Ute

    2016-07-01

    Cerebral cavernous malformations (CCMs) are prevalent slow-flow vascular lesions which harbour the risk to develop intracranial haemorrhages, focal neurological deficits, and epileptic seizures. Autosomal dominantly inherited CCMs were found to be associated with heterozygous inactivating mutations in 3 genes, CCM1 (KRIT1), CCM2 (MGC4607), and CCM3 (PDCD10) in 1999, 2003 and 2005, respectively. Despite the availability of high-throughput sequencing techniques, no further CCM gene has been published since. Here, we report on the identification of an autosomal dominantly inherited frameshift mutation in a gene of thus far unknown function, FAM222B (C17orf63), through exome sequencing of CCM patients mutation-negative for CCM1-3. A yeast 2-hybrid screen revealed interactions of FAM222B with the tubulin cytoskeleton and STAMBP which is known to be associated with microcephaly-capillary malformation syndrome. However, a phenotype similar to existing models was not found, neither in fam222bb/fam222ba double mutant zebrafish generated by transcription activator-like effector nucleases nor in an in vitro sprouting assay using human umbilical vein endothelial cells transfected with siRNA against FAM222B. These observations led to the assumption that aberrant FAM222B is not involved in the formation of CCMs. PMID:27587990

  8. Identification of FAM96B as a novel prelamin A binding partner

    SciTech Connect

    Xiong, Xing-Dong; Wang, Junwen; Zheng, Huiling; Jing, Xia; Liu, Zhenjie; Zhou, Zhongjun; Liu, Xinguang

    2013-10-11

    Highlights: •We screen the binding protein of prelamin A by yeast two-hybrid screen. •FAM96B colocalizes with prelamin A in HEK-293 cells. •FAM96B physically interacts with prelamin A. -- Abstract: Prelamin A accumulation causes nuclear abnormalities, impairs nuclear functions, and eventually promotes cellular senescence. However, the underlying mechanism of how prelamin A promotes cellular senescence is still poorly understood. Here we carried out a yeast two-hybrid screen using a human skeletal muscle cDNA library to search for prelamin A binding partners, and identified FAM96B as a prelamin A binding partner. The interaction of FAM96B with prelamin A was confirmed by GST pull-down and co-immunoprecipitation experiments. Furthermore, co-localization experiments by fluorescent confocal microscopy revealed that FAM96B colocalized with prelamin A in HEK-293 cells. Taken together, our data demonstrated the physical interaction between FAM96B and prelamin A, which may provide some clues to the mechanisms of prelamin A in premature aging.

  9. Chemotherapy for Soft Tissue Sarcomas

    MedlinePlus

    ... drugs may be used as well, including cisplatin, dacarbazine (DTIC), docetaxel (Taxotere ® ), gemcitabine (Gemzar ® ), methotrexate, oxaliplatin, paclitaxel (Taxol ® ), ... such as: MAID (mesna, Adriamycin [doxorubicin], ifosfamide, and dacarbazine). Chemotherapy drugs kill cancer cells but also damage ...

  10. Sequence of Radiotherapy and Chemotherapy in Breast Cancer After Breast-Conserving Surgery

    SciTech Connect

    Jobsen, Jan J.; Palen, Job van der; Brinkhuis, Marieel; Ong, Francisca; Struikmans, Henk

    2012-04-01

    Purpose: The optimal sequence of radiotherapy and chemotherapy in breast-conserving therapy is unknown. Methods and Materials: From 1983 through 2007, a total of 641 patients with 653 instances of breast-conserving therapy (BCT), received both chemotherapy and radiotherapy and are the basis of this analysis. Patients were divided into three groups. Groups A and B comprised patients treated before 2005, Group A radiotherapy first and Group B chemotherapy first. Group C consisted of patients treated from 2005 onward, when we had a fixed sequence of radiotherapy first, followed by chemotherapy. Results: Local control did not show any differences among the three groups. For distant metastasis, no difference was shown between Groups A and B. Group C, when compared with Group A, showed, on univariate and multivariate analyses, a significantly better distant metastasis-free survival. The same was noted for disease-free survival. With respect to disease-specific survival, no differences were shown on multivariate analysis among the three groups. Conclusion: Radiotherapy, as an integral part of the primary treatment of BCT, should be administered first, followed by adjuvant chemotherapy.

  11. The adjuvancy of silicones: dependency on compartmentalization.

    PubMed

    Klykken, P C; White, K L

    1996-01-01

    Studies have been conducted in mice (B6C3F1) and rats (Sprague Dawley, Fischer 344) to investigate the adjuvancy potential of silicone mammary gel and the low molecular weight silicone fluid, octamethylcyclotetrasiloxane (D4). Dependent on the experimental conditions employed, a divergent data profile emerges. If the antigen (bovine serum albumin, BSA) is emulsified with either the gel or the D4 prior to intramuscular immunization, an amplified anti-BSA IgG antibody response, as measured by multipoint ELISA methodology, is noted over the 8 week measurement period. In parallel studies, a variety of non-silicone personal care ingredients (lanolin, white mineral oil, isopropyl palmitate) were also capable of amplifying this humoral response relative to the non-adjuvant phosphate buffered saline control. These observations are consistent with the empirical knowledge that hydrophobic substances tend to augment immune responses. However, under conditions in which the antigen is not blended with the silicone prior to immunization, normal immune responses are noted. In short (10 day) and long (180 day) term gel implant studies, the optimal IgM and IgG antibody responses, as determined in the antibody forming cell assay, were equivalent between the gel implanted and control animals. Moreover, under similar exposure conditions, no adjuvancy was noted in the three Host Resistance models (B16F10 Melanoma, Listeria monocytogenes, and Streptococcus pneumoniae) tested. Antibody forming cell studies conducted after 28 days of oral or inhalation exposure to D4 have also yielded responses similar to the non-silicone exposed vehicle controls. Collectively, these data suggest that in the absence of premixing the antigen with the silicone test material, there does not appear to be any silicone induced adjuvant response. PMID:8565549

  12. Carboplatin versus alternating carboplatin and doxorubicin for the adjuvant treatment of canine appendicular osteosarcoma: a randomized, phase III trial†

    PubMed Central

    Skorupski, K. A.; Uhl, J. M.; Szivek, A; Allstadt Frazier, S. D.; Rebhun, R. B.; Rodriguez, C. O.

    2016-01-01

    Despite numerous published studies describing adjuvant chemotherapy for canine appendicular osteosarcoma, there is no consensus as to the optimal chemotherapy protocol. The purpose of this study was to determine whether either of two protocols would be associated with longer disease-free interval (DFI) in dogs with appendicular osteosarcoma following amputation. Dogs with histologically confirmed appendicular osteosarcoma that were free of gross metastases and underwent amputation were eligible for enrollment. Dogs were randomized to receive either six doses of carboplatin or three doses each of carboplatin and doxorubicin on an alternating schedule. Fifty dogs were included. Dogs receiving carboplatin alone had a significantly longer DFI (425 versus 135 days) than dogs receiving alternating carboplatin and doxorubicin (P = 0.04). Toxicity was similar between groups. These results suggest that six doses of carboplatin may be associated superior DFI when compared to six total doses of carboplatin and doxorubicin. PMID:24118677

  13. Melanoma and IFN alpha: potential adjuvant therapy.

    PubMed

    Bottoni, U; Clerico, R; Paolino, G; Corsetti, P; Ambrifi, M; Brachini, A; Richetta, A; Nisticò, S; Pranteda, G; Calvieri, S

    2014-01-01

    Interferon alpha (IFNalpha) is the most used adjuvant treatment in clinical practice for melanoma (MEL) high-medium risk patients; however, the use of IFNalpha has yielded conflicting data on Overall Survival (OS) and disease free survival (DFS) rates. Starting from these considerations, we carried out an analysis on our MEL patients who received adjuvant IFNalpha therapy, in order to identify possible predictors for their outcome. A total of 140 patients were included in our analysis. Patients with Breslow thickness ≤2.00 mm presented a significantly longer mean DFS than patients with Breslow ≥2.01 mm (p = 0.01). Using non- parametric Spearman’s Coefficient test we found association between DFS and Breslow thickness (p < 0.001) and between DFS and ulceration (p = 0.03). Performing Multiple Regression test, Breslow thickness (p < 0.001) remained the only statistically significant predictor. From the OS analysis we found that patients with lower Breslow values ≤ 2.00 mm (p < 0.0001), and absence of ulceration (p <0.004) showed a significantly better long-term survival. From the current analysis we found that the use of low dose IFNalpha is justified only for cutaneous melanoma ≤ 4.01 mm that was not ulcerated; patients with Breslow ≥ 4.01 mm, in our opinion, should not carry out adjuvant treatment with low dose IFNalpha, because its side effects could be higher than the its benefits. PMID:25001659

  14. Efficacy of live adjuvanted mesogenic Newcastle disease vaccine in chickens.

    PubMed

    Roy, P; Venugopalan, A T; Koteeswaran, A

    1999-06-01

    120 white leghorn chickens primed with a lentogenic Newcastle disease (ND) live vaccine at 7 days of age were divided into three equal groups of 8 weeks of age and vaccinated with a live mesogenic ND vaccine (NDV). One group received only Newcastle disease mesogenic vaccine (RDVK) in normal saline, the second group received RDVK with groundnut oil as adjuvant and the third group received RDVK with liquid paraffin as adjuvant. Sera were collected at different time points for the assessment of antibody level against ND virus (NDV) by the haemagglutination inhibition (HI) test. The commonly used non-adjuvanted RDVK could not evince 100% protective HI titre beyond 11 weeks of age but in both the adjuvanted groups 100% protective HI titre was evident up to 20 weeks of age. On challenge at 20 weeks of age both the adjuvanted groups withstood challenge but in the non-adjuvanted group 80% of chickens withstood the challenge. A significant difference in immune response between the adjuvanted and non-adjuvanted groups was seen but not between both the adjuvanted groups. The advantage of vegetable oil (groundnut oil) as an adjuvant for live mesogenic ND vaccine has been discussed. PMID:10418918

  15. Recent Advances of Vaccine Adjuvants for Infectious Diseases

    PubMed Central

    Nguyen, Minh Trang

    2015-01-01

    Vaccines are the most effective and cost-efficient method for preventing diseases caused by infectious pathogens. Despite the great success of vaccines, development of safe and strong vaccines is still required for emerging new pathogens, re-emerging old pathogens, and in order to improve the inadequate protection conferred by existing vaccines. One of the most important strategies for the development of effective new vaccines is the selection and usage of a suitable adjuvant. Immunologic adjuvants are essential for enhancing vaccine potency by improvement of the humoral and/or cell-mediated immune response to vaccine antigens. Thus, formulation of vaccines with appropriate adjuvants is an attractive approach towards eliciting protective and long-lasting immunity in humans. However, only a limited number of adjuvants is licensed for human vaccines due to concerns about safety and toxicity. We summarize current knowledge about the potential benefits of adjuvants, the characteristics of adjuvants and the mechanisms of adjuvants in human vaccines. Adjuvants have diverse modes of action and should be selected for use on the basis of the type of immune response that is desired for a particular vaccine. Better understanding of current adjuvants will help exploring new adjuvant formulations and facilitate rational design of vaccines against infectious diseases. PMID:25922593

  16. Radiation and concurrent chemotherapy for the treatment of Lewis lung tumor and B16 melanoma tumor in C57/BL mice

    SciTech Connect

    Pedersen, J.E.; Barron, G.

    1984-08-01

    C57/BL mice bearing either Lewis lung tumor or B16 melanoma tumor were treated with radiation and concurrent chemotherapy. The treatment results were determined in vivo by tumor regrowth delay assay. When continuous infusion of either Cyclophosphamide (CYCLO) or 5-Fluorouracil (5-FU) or Adriamycin (ADRIA) or Mitomycin-C (MITO-C) was used in combination with continuous radiation at 1 cGy/min, no increase in tumor regrowth delay was observed over that of radiation alone. When multiple drug chemotherapy, FAM (5-FU, ADRIA, MITO-C) was administered in combination with radiation at 80 cGy/min, no increase in tumor regrowth delay was observed over that of radiation alone. In these two murine tumor models, when clinically relevant concentrations of commonly used chemotherapy agents were combined with radiation, no therapeutic advantage was observed.

  17. The SNP rs6500843 in 16p13.3 is associated with survival specifically among chemotherapy-treated breast cancer patients.

    PubMed

    Fagerholm, Rainer; Schmidt, Marjanka K; Khan, Sofia; Rafiq, Sajjad; Tapper, William; Aittomäki, Kristiina; Greco, Dario; Heikkinen, Tuomas; Muranen, Taru A; Fasching, Peter A; Janni, Wolfgang; Weinshilboum, Richard; Loehberg, Christian R; Hopper, John L; Southey, Melissa C; Keeman, Renske; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Chenevix-Trench, Georgia; Lambrechts, Diether; Wildiers, Hans; Chang-Claude, Jenny; Seibold, Petra; Couch, Fergus J; Olson, Janet E; Andrulis, Irene L; Knight, Julia A; García-Closas, Montserrat; Figueroa, Jonine; Hooning, Maartje J; Jager, Agnes; Shah, Mitul; Perkins, Barbara J; Luben, Robert; Hamann, Ute; Kabisch, Maria; Czene, Kamila; Hall, Per; Easton, Douglas F; Pharoah, Paul D P; Liu, Jianjun; Eccles, Diana; Blomqvist, Carl; Nevanlinna, Heli

    2015-04-10

    We have utilized a two-stage study design to search for SNPs associated with the survival of breast cancer patients treated with adjuvant chemotherapy. Our initial GWS data set consisted of 805 Finnish breast cancer cases (360 treated with adjuvant chemotherapy). The top 39 SNPs from this stage were analyzed in three independent data sets: iCOGS (n=6720 chemotherapy-treated cases), SUCCESS-A (n=3596), and POSH (n=518). Two SNPs were successfully validated: rs6500843 (any chemotherapy; per-allele HR 1.16, 95% C.I. 1.08-1.26, p=0.0001, p(adjusted)=0.0091), and rs11155012 (anthracycline therapy; per-allele HR 1.21, 95% C.I. 1.08-1.35, p=0.0010, p(adjusted)=0.0270). The SNP rs6500843 was found to specifically interact with adjuvant chemotherapy, independently of standard prognostic markers (p(interaction)=0.0009), with the rs6500843-GG genotype corresponding to the highest hazard among chemotherapy-treated cases (HR 1.47, 95% C.I. 1.20-1.80). Upon trans-eQTL analysis of public microarray data, the rs6500843 locus was found to associate with the expression of a group of genes involved in cell cycle control, notably AURKA, the expression of which also exhibited differential prognostic value between chemotherapy-treated and untreated cases in our analysis of microarray data. Based on previously published information, we propose that the eQTL genes may be connected to the rs6500843 locus via a RBFOX1-FOXM1 -mediated regulatory pathway. PMID:25823661

  18. The SNP rs6500843 in 16p13.3 is associated with survival specifically among chemotherapy-treated breast cancer patients

    PubMed Central

    Fagerholm, Rainer; Schmidt, Marjanka K.; Khan, Sofia; Rafiq, Sajjad; Tapper, William; Aittomäki, Kristiina; Greco, Dario; Heikkinen, Tuomas; Muranen, Taru A.; Fasching, Peter A.; Janni, Wolfgang; Weinshilboum, Richard; Loehberg, Christian R.; Hopper, John L.; Southey, Melissa C.; Keeman, Renske; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Chenevix-Trench, Georgia; Investigators, kConFab; Lambrechts, Diether; Wildiers, Hans; Chang-Claude, Jenny; Seibold, Petra; Couch, Fergus J.; Olson, Janet E.; Andrulis, Irene L.; Knight, Julia A.; García-Closas, Montserrat; Figueroa, Jonine; Hooning, Maartje J.; Jager, Agnes; Shah, Mitul; Perkins, Barbara J.; Luben, Robert; Hamann, Ute; Kabisch, Maria; Czene, Kamila; Hall, Per; Easton, Douglas F.; Pharoah, Paul D.P.; Liu, Jianjun; Eccles, Diana; Blomqvist, Carl; Nevanlinna, Heli

    2015-01-01

    We have utilized a two-stage study design to search for SNPs associated with the survival of breast cancer patients treated with adjuvant chemotherapy. Our initial GWS data set consisted of 805 Finnish breast cancer cases (360 treated with adjuvant chemotherapy). The top 39 SNPs from this stage were analyzed in three independent data sets: iCOGS (n=6720 chemotherapy-treated cases), SUCCESS-A (n=3596), and POSH (n=518). Two SNPs were successfully validated: rs6500843 (any chemotherapy; per-allele HR 1.16, 95% C.I. 1.08-1.26, p=0.0001, p(adjusted)=0.0091), and rs11155012 (anthracycline therapy; per-allele HR 1.21, 95% C.I. 1.08-1.35, p=0.0010, p(adjusted)=0.0270). The SNP rs6500843 was found to specifically interact with adjuvant chemotherapy, independently of standard prognostic markers (p(interaction)=0.0009), with the rs6500843-GG genotype corresponding to the highest hazard among chemotherapy-treated cases (HR 1.47, 95% C.I. 1.20-1.80). Upon trans-eQTL analysis of public microarray data, the rs6500843 locus was found to associate with the expression of a group of genes involved in cell cycle control, notably AURKA, the expression of which also exhibited differential prognostic value between chemotherapy-treated and untreated cases in our analysis of microarray data. Based on previously published information, we propose that the eQTL genes may be connected to the rs6500843 locus via a RBFOX1-FOXM1-mediated regulatory pathway. PMID:25823661

  19. Surgical resection with adjuvant brachytherapy in soft tissue sarcoma of the extremity – a case report

    PubMed Central

    Łyczek, Jarosław; Kowalik, Łukasz

    2012-01-01

    Purpose Surgery is the major therapeutic method in soft tissue sarcomas of the extremity (E-STS). Treatment of large high-grade tumours, which resection cannot be performed with a wide safe margin, should include complementary radiation and/or chemo-therapy. Hopefully, the use of adjuvant brachytherapy will improve the prognosis of E-STS. Case description After a long process of diagnosing a tumour in the medial compartment of the thigh, a 65-year-old woman with diagnosed synovial sarcoma underwent a sur