Gemcitabine plus Cisplatin versus Gemcitabine plus Carboplatin as First-Line Chemotherapy in Advanced Transitional Cell Carcinoma of the Urothelium: Results of a Randomized Phase 2 Trial

ObjectivesThis phase 2 randomized study compared the toxicity and assessed the efficacy of gemcitabine–cisplatin (GP) and gemcitabine–carboplatin (GC) in patients with advanced transitional cell carcinoma of the urothelium (TCC), with the main objective to demonstrate a reduction in toxicity of at least 25% in the GC arm.MethodsA total of 110 chemonaive patients (55 per arm) with locally advanced or metastatic TCC received gemcitabine 1250 mg/m2 on days 1 and 8 plus cisplatin 70 mg/m2 on day 2 (GP) every 3 wk or gemcitabine 1250 mg/m2 on days 1 and 8 plus carboplatin AUC 5 on day 2 (GC) every 3 wk for a maximum of six cycles.ResultsNo differences between arms were noted in the overall toxicity profiles and any parameter of toxicity. The most frequent grade 3–4 hematologic toxicity was neutropenia in 34.6% of patients for GP and 45.4% for GC. The most frequent grade 3–4 nonhematologic toxicity was nausea and vomiting (GP: 9.1%; GC: 3.6%). Grade 1–2 nephrotoxicity occurred in 14 GP-treated patients (26.0%) and 9 GC-treated patients (16.3%). Per an intent-to-treat analysis, overall response, evaluated on 80 patients, was 49.1% for GP (CR: 14.5%; PR: 34.5%) and 40.0% for GC (CR: 1.8%; PR: 38.2%). Median time to progression was 8.3 mo for GP and 7.7 mo for GC. Median survival was 12.8 mo and 9.8 mo for GP and GC, respectively.ConclusionsGC has a comparably acceptable toxicity profile compared with that of GP and seems active in patients with TCC.