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Background : Cisplatin-based combination chemotherapy before surgery is the standard of care for muscle-invasive bladder cancer. However, the optimal chemotherapy modalities have not been precisely defined to date. Patients and Methods : In the VESPER trial, patients received after randomization either gemcitabine and cisplatin (GC, 4 cycles) or methotrexate, vinblastine, doxorubicin and cisplatin (dose dense [dd]-MVAC, 6 cycles). Creatinine clearance (CrCl) was calculated before each cycle according to the Cockroft and Gault formula. Definition criteria for local control after neoadjuvant chemotherapy included pathological complete response (ypT0N0), pathological downstaging ( Results : A total of 2,128 cycles of chemotherapy were delivered, including 2,120 (99.6%) with cisplatin. Full doses of cisplatin were given in 1866 (88%) cycles. Twenty-three (4.7%) patients had to stop chemotherapy (12 GC, 11 dd-MVAC) because of renal failure. No difference in CrCl median values was observed between the two regimens during the first four cycles. A mild decrease occurred thereafter in patients treated with two additional cycles of dd-MVAC. A minimum total dose of 270 mg/m2 for cisplatin was mandatory to optimize pathological complete responses. Conclusion : At least 4 cycles of cisplatin-based chemotherapy should be delivered before cystectomy. Increasing the number of cycles beyond 4 cycles does not lead to a clinically significant deterioration in renal function but without obvious gain on local control. MicroAbstractCGC : A deep analysis of data from a randomized trial of perioperative chemotherapy in muscle-invasive bladder cancer shows that a minimum number of 4 cycles is required to optimize the chances of pathological complete response at cystectomy. Increasing the number beyond 4 cycles does not lead to a clinically significant deterioration in renal function without any obvious gain on pathological complete response.

This study looked at whether epidermal growth factor receptor inhibition by the monoclonal antibody panitumumab could increase the efficacy of standard chemotherapy in advanced urothelial cancer. Results were disappointing, with higher toxicity and no improvement in efficacy in the combination arm. Background: Epidermal growth factor receptor (EGFR) overexpression is frequent and associated with poor outcome in urothelial carcinoma. EGFR inhibition could improve the antitumor activity of chemotherapy. Patients and Methods: Patients with advanced, treatment-naive, histologically confirmed advanced urothelial carcinoma and no HRAS or KRAS mutation in the primary tumor received dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) without or with the anti-EGFR monoclonal antibody panitumumab (Pmab). A randomized (1:2) phase II design was used with progression-free survival (PFS) as the primary endpoint. Results: Ninety-seven eligible patients were randomized; 96 patients were evaluable for toxicity and 87 for efficacy. The median PFS were 6.8 months (95% confidence interval [CI], 6.3-9.2) for dd-MVAC and 5.7 months (95% CI, 4.6-6.4 months) for dd-MVAC+Pmab. For both immunohistochemical and molecular definition of basal/squamous-like (BASQ) tumors, no difference was observed in objective response rates or PFS between the two arms in BASQ and non-BASQ tumors. Conclusion: dd-MVAC+Pmab was associated with more serious adverse events and no improvement in efficacy outcomes.

Administration of cytotoxic chemotherapy for patients with metastatic cancer and poor performance status is a daily clinical challenge. Guidelines only help to select a therapeutic regimen but do not offer a clear response whether or not the patients should be treated. We performed a prospective analysis in 139 metastatic patients with performance status > 1 according to the Eastern Cooperative Oncology Group scale. A decision was considered correct if patients treated with a medical anticancer treatment lived over 3 months or alternatively patients not treated had a survival under 3 months. The predominant tumor type was non-small cell lung cancer. Patients were chemotherapy naive in 87 cases (63 %). A new line of medical anticancer treatment was started in 107 cases (77 %). The median survival of the study population was 11 weeks (range, 1-53). 84 patients (60 %) died within 3 months while 55 patients (40 %) lived more than 3 months after decision. Treatment decisions were considered as appropriate in 81 cases (58 %). No patient was considered as undertreated. The analysis by pathology allowed to identify pathologies where decisions were correct in the majority of the cases (renal, urothelial and small cell lung cancers), pathologies where appropriate and inappropriate decisions were balanced (prostate, ovarian and breast cancers) and pathologies where decisions for treatment were excessive (non-small cell lung cancer and unknown primary). This prospective study was conducted as part of the evaluation of professional practices in our department. Administration of a medical anticancer treatment validated with patients with good performance status may be harmful for patients with poor performance status. The findings resulted in recommendations for daily practice in order to help physicians, especially for the "don't go" decisions. Until the identification of new prognostic factors for survival and/or the development of therapies making sensitive currently chemoresistant diseases, the initiation of a medical anticancer treatment outside standard situations should result from a consensual decision team or the inclusion in a clinical trial.

The microtubule inhibitor vinflunine is currently the only cytotoxic drug approved in Europe for the treatment of patients with metastatic transitional cell carcinoma who failed first-line platinum-based chemotherapy. Indeed, the only Phase III trial ever conducted in this setting demonstrated a benefit in progression-free and overall survival for patients receiving vinflunine plus best supportive care compared with best supportive care alone. Recent data from European studies performed in real life confirmed the efficacy of the drug, even in patient populations exhibiting adverse prognostic factors. Side effects were manageable, provided gastrointestinal prophylaxis is performed. The potential role of vinflunine in first-line treatment as maintenance therapy or as a partner in combination chemotherapy for patients unfit for cisplatin is currently being investigated.

Purpose: Response Evaluation Criteria in Solid Tumors (RECIST) may underestimate the efficacy of targeted therapies. In hepatocellular carcinoma (HCC) studies with sunitinib, RECIST-defined response rates are low, although hypodensity on computed tomography (CT) scans occurs more frequently. This exploratory analysis investigated tumor density as a surrogate endpoint of sunitinib activity in a phase II HCC study. Experimental Design: Patients received sunitinib 50 mg/d (4 weeks on/2 weeks off). Tumor size and density were assessed on CT scans by using RECIST and Choi criteria, the latter of which classify a partial response as a 15% or more reduction in tumor density or a 10% or more reduction in tumor size. The overall percentage volume of tumor necrosis was calculated with volumetric reconstruction. Tumor perfusion parameters were assessed by using perfusion CT scans with specific acquisition. Results: Among the 26 evaluable patients, 1 achieved a partial response and 22 had tumor stabilization by RECIST. In analysis of tumor density, 17 of 26 patients (65.4%) were responders by Choi criteria. Volumetric assessment showed major tumor necrosis (≥30% of tumor volume) in 10 of 21 patients (47.6%). Among four patients evaluated, tumor blood flow was reduced by 58.8% and blood volume by 68.4% after 4 weeks of treatment. The median time to progression (TTP) was 6.4 months. Patients with responses by Choi criteria had a significantly longer TTP (7.5 months) compared with nonresponders (4.8 months; HR = 0.33, two-sided P = 0.0182). Conclusions: Tumor density assessment suggested that radiologic endpoints in addition to RECIST may be considered to capture sunitinib activity in HCC. Clin Cancer Res; 17(13); 4504–12. ©2011 AACR.

Disseminated intravascular coagulation (DIC) is a rare, potentially life-threatening complication of advanced prostate carcinoma. We report the successful treatment with abiraterone acetate of acute DIC related to a progressive bone metastatic disease in a chemotherapy-naïve patient with castrate-resistant prostate cancer.

Among neuroendocrine carcinomas of the gut, well-differentiated tumors are highly vascularized, featuring specific characteristics on contrast-enhanced imaging. Well-differentiated neuroendocrine tumors spontaneously harbor hypervascular enhancement, coexisting with areas of necrosis mainly located at the center of tumor lesions. When exposed to vascular endothelial growth factor (VEGFR) inhibitors such as sunitinib, target lesions display few if any variation in tumor size, but rather detectable modifications in tumor density. In several patients treated with targeted therapy, a significant decrease of tumor density at first tumor evaluation can be detected as compared to baseline. Consistently, the two randomized trials leading to approval of sunitinib and everolimus in pancreatic neuroendocrine tumors report objective response rate below 10 %, emphasizing that Response Evaluation Criteria in Solid Tumors (RECIST), that focus only on the largest diameters of target lesions, may be insufficient to capture the full benefit of targeted therapies. Alternative criteria, such as those developed by Choi et al., consider both the size and the density of the tumor as parameters for response evaluation. Choi criteria have been recently proposed as a surrogate endpoint for efficacy and to identify patients that are good responders to VEGFR inhibitors such as sunitinib and sorafenib in advanced hepatocellular carcinoma, another disease highly addicted to angiogenesis. Preliminary data generated from patients included in the sunitinib phase III trial suggest that Choi criteria might also be considered as an alternative to RECIST to evaluate the effects of sunitinib in patients with advanced well-differentiated neuroendocrine tumors.

La validation du sorafenib dans le carcinome hepatocellulaire (CHC) avance a permis un progres majeur dans la prise en charge des patients atteints de cette maladie et a entraine un deferlement d'investigations portant sur des agents cibles dans cette pathologie. Un concept important est que la tolerance et l'efficacite de cet agent reposent sur une selection optimale des patients. Cependant, plusieurs questions pertinentes restent non resolues concernant l'utilisation du sorafenib en routine clinique. En effet, si le sorafenib a permis une amelioration significative de la survie globale des patients atteints d'un CHC avance sur cirrhose Child A comparativement au placebo, ceci contraste avec de faibles taux de reponse obtenus par cette molecule selon les criteres RECIST. Ainsi, de nouveaux parametres integrant des modifications de densite intratumorale pourraient etre pris en compte en plus des criteres dimensionnels pour juger de l'efficacite objective de cette drogue. Actuellement, les recherches en cours doivent definir la place des antiangiogeniques en association avec les autres approches therapeutiques et identifier des biomarqueurs fiables predictifs de reponse.