A Phase II Study of the Central European Society of Anticancer-Drug Research (CESAR) Group: Results of an Open-Label Study of Gemcitabine plus Cisplatin with or without Concomitant or Sequential Gefitinib in Patients with Advanced or Metastatic Transitional Cell Carcinoma of the Urothelium (original) (raw)
Related papers
Cancer, 2006
BACKGROUND. The toxicity of platinum-based combinations represents a common problem for patients with advanced urothelial carcinoma. The authors previously reported encouraging efficacy for the combination of carboplatin and gemcitabine in patients considered to be unfit for cisplatin-based treatment. The objective of the current multicenter Phase II study was to evaluate the safety and efficacy of the combination of gemcitabine and carboplatin as first-line treatment in unselected patients with advanced urothelial carcinoma. METHODS. Patients with previously untreated, bidimensionally measurable, inoperable or metastatic urothelial carcinoma were treated with carboplatin, area under the concentration curve of 5 (Day 1) and gemcitabine at a dose of 1000 mg/m 2 (Days 1 and 8), every 21 days for a total of 6 cycles. RESULTS. Sixty patients (49 men and 11 women, with a median age of 69 yrs) were enrolled in the current study. Intent-to-treat analysis demonstrated an objective response rate (ORR) of 38.4% (95% confidence interval [95% CI], 26 -51.8%) (11.7% complete responses and 26.7% partial responses). The median time to disease progression was 7.6 months (95% CI, 4.5-10.7 mos) and the median overall survival was 16.3 months (95% CI, 12-20.6 mos). The median survival was comparable to that reported for the combination of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) according to the Memorial Sloan-Kettering Cancer Center prognostic model for patients with similar baseline prognostic features. Grade 3 or 4 toxicity (according to the National Cancer Institute Common Toxicity Criteria [version 2.0]) included anemia (18%), thrombocytopenia (23%), and neutropenia (52%), with 7 episodes of febrile neutropenia (11%) reported. Nonhematologic toxicity was rare. One toxic death occurred during the study.
Gemcitabine in the treatment of advanced transitional cell carcinoma of the urothelium
Annals of Oncology, 2006
M-VAC (cisplatin, methotrexate, adriamycin, vinblastine) combination chemotherapy has been for long time the standard of care in fit patient with advanced urothelial tumors. Gemcitabine/cisplatin with similar results and an improved toxicity profile has proved to be a new standard alternative. Whether or not we can improve survival with newer triplet regimens will depend upon the results of ongoing phase III trials. In addition to the new active drug combinations and targeted therapies, new approaches are emerging for treatment. Chemotherapy optimization using molecular markers predicting chemosensitivity are being applied. There is an obvious need to incorporate in clinical trials a systematic translational approach to explain both our successes and our failures.
2011
The primary objective of this study was to determine the response rate of the combination carboplatin and gemcitabine in patients with advanced and/or metastatic transitional cell carcinoma (TCC). The secondary objective was to evaluate the safety profile and overall survival. Patients and methods: Patients were treated with gemcitabine 1000 mg/m² on days 1 and 8 and carboplatin area under the concentration-time curve 5 on day 1 every 21 days. Results: 23 patients were included onto the trial. 18 patients were included for response analysis: 1 patient (5.6%) showed a complete response and 7 patients (38.9%) achieved a partial response for an overall response rate of 44.4% (95% Confidence Interval (CI): 21.5%-67.4%) with a median overall survival of 5.2 months (95% CI: 0-10.8 months). Stable disease was observed in 6 patients and progressive disease in 4 patients. The response rate and median survival for the intent to treat population were respectively 34.8% (95% CI: 14.6-53.4%) and 3.3 months (95% CI: 0-6.9 months). Grades 3 and 4 anaemia, thrombocytopenia and neutropenia were observed respectively in 9, 13, and 11 patients. Grades 3 and 4 nonhaematological toxicities were fatigue in 2 patients, renal failure in 2 patients, pain in 2 patients, haematuria in 2 patients and 8 patients developed infectious complications. There was 1 toxic death. Conclusion: The gemcitabine plus carboplatin combination is active and has a manageable toxicity in patients with advanced and/or metastatic TCC. A global geriatric assessment is recommended to identify patients who would not benefit from intensive chemotherapy.
European Urology, 2014
Gemcitabine and cisplatin chemotherapy (GC regimen) represents a standard treatment for advanced urothelial carcinoma. We performed an open-label, single-arm, non-randomised, phase 2 trial evaluating the addition of sunitinib to standard GC chemotherapy (SGC regimen). Overall, 63 treatment-naïve participants were recruited and received up to six 21-d cycles of cisplatin 70 mg/m 2 (intravenously [IV], day 1) and gemcitabine 1000 mg/m 2 (IV, days 1 and 8) combined with sunitinib 37.5 mg (orally, days 2-15). Following review of toxicity after the first six patients, the sunitinib dose was reduced to 25 mg for all patients. Overall response rate was 64%, with response noted in 37 of 58 patients. At 6 mo, 30 of 58 assessable patients (52%; 90% confidence interval [CI], 40-63%) were progression free. Median overall survival was 12 mo (95% CI, 9-15) and was heavily influenced by Bajorin prognostic group. Grade 3-4 toxicities were predominantly haematologic and limited the deliverability of the triple SGC regimen. The trial did not meet its prespecified primary end point of >60% patients progression free at 6 mo. Cumulative myelosuppression led to treatment delays of gemcitabine and cisplatin and dose reduction and/or withdrawal of sunitinib in the majority of cases. The triple-drug combination was not well tolerated. Phase 3 evaluation of the triple SGC regimen in advanced transitional cell carcinoma is not recommended. Patient summary: The addition of sunitinib to standard cisplatin and gemcitabine chemotherapy was poorly tolerated and did not improve outcomes in advanced urothelial carcinoma. Treatment delivery was limited by myelotoxicity.
Annals of Oncology, 2001
Purpose: To evaluate the activity and toxicity of gemcitabine and carboplatin in consecutive patients presenting with locally advanced or metastatic transitional cell carcinoma of the urothelium (TCC). Patients and methods: Seventeen consecutive patients referred to a single institution with locally advanced or metastatic TCC were treated with carboplatin AUC 5 on day 1 and gemcitabine 1000 mg/m 2 on day 1 and 8 of a 21-day cycle. All patients were assessable for response and toxicity. Minimal eligibility criteria were used to minimize patient selection. Results: Seventeen patients with measurable stage IV TCC of the urothelium were treated. The median age was 69 years (range 54-78), the median creatinine clearance was 56 ml/min (range 34-90) and 30% of patients had an ECOG performance score of two. Nine patients (53%) had visceral metastases and the majority of patients had multiple sites of metastases. There were three complete responses, seven partial responses, for an overall response rate of 58.8%. Responses were seen at all sites including the liver. One patient had a response within a previously irradiated field and three patients with prior chemotherapy had responses. Median overall survival was 10.5 months and median time to progression was 4.6 months. Toxicity was primarily haematologic with six patients having grade 3 neutropenia and six patients with grade 4 neutropenia. There were five cases of grade 3 and three cases of grade 4 thrombocytopenia. There were no episodes of febrile neutropenia and only one patient required admission for management of toxicity. Thirteen patients required dose reduction or delay due to neutropenia or thrombocytopenia. There were no treatmentrelated deaths. Conclusion: The combination of carboplatin and gemcitabine is active in metastatic transitional cell carcinoma of the urothelium with manageable toxicity in a relatively elderly group of patients with some poor prognostic features.