Gemcitabine plus cisplatin for advanced transitional cell carcinoma of theurinary tract: A phase II multicenter trial

Purpose: We determined the activity and toxicity of gemcitabine plus cispla tin in patients with inoperable or metastatic transitional cell carcinoma o f the urinary tract. Materials and Methods: A total of 54 patients with transitional cell carcin oma, measurable disease and Eastern Cooperative Oncology Group performance status 2 or greater were enrolled in this multicenter phase II trial. Previ ous adjuvant or neoadjuvant therapy for locally advanced disease was accept able if it had been completed more than 1 year before study entry. Every 4 weeks patients received 1,000 mg./m.(2) gemcitabine intravenously on days 1 , 8 and 15, and 70 mg./m.(2) cisplatin intravenously on day 2. Results: All patients were evaluable for response and toxicity. Notably onl y 7 of the 54 patients (13%) previously received chemotherapy in an adjuvan t or neoadjuvant setting. Overall we observed 26 objective responses (48%), of which 15% were complete. Median time to progression was 23 weeks and me dian survival was 54 weeks. Treatment was well tolerated. The main toxiciti es were leukopenia (grade 3 in 28% and grade 4 in 11% of patients), anemia (grade 3 in 34% and grade 4 in 6%) and thrombocytopenia (grade 3 in 14% and grade 4 in 6%). Other relevant side effects were nausea and vomiting in 20 % of cases, fever in 24%, alopecia in 22%, renal failure in 7.4% and mucosi tis in 2%. Conclusions: Combined cisplatin plus gemcitabine is highly active in advanc ed transitional cell carcinoma of the urinary tract with manageable toxicit y. The response rate, time to treatment failure and overall survival appear ed to be comparable to those achieved with combined methotrexate, vinblasti ne, doxorubicin and cisplatin. Conversely toxicity appeared lower. Evaluati on of this regimen in randomized studies with methotrexate, vinblastine, do xorubicin and cisplatin is strongly suggested.