The combination of gemcitabine and carboplatin as first-line treatment in patients with advanced urothelial carcinoma - A Phase II study of the Hellenic Cooperative Oncology Group

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 tinder 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% Cl, 4.5-10.7 mos) and the median overall survival was 16.3 months (95% Cl, 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. Non-hematologic toxicity was rare. One toxic death occurred during the study. CONCLUSIONS. The combination of gemcitabine and carboplatin appears to have considerable activity as the first-line treatment Of Unselected patients with advanced urothelial carcinoma with manageable toxicity, and deserves further evaluation in this setting.