PHASE-II TRIAL OF PACLITAXEL AND CARBOPLATIN IN THE TREATMENT OF ADVANCED UROTHELIAL CARCINOMA

Purpose: Both paclitaxel and carboplatin have single-agent activity ag ainst carcinoma of the urothelium. We evaluated the combination of pac litaxel and carboplatin in the treatment of advanced cancers of the ur othelium. Patients and Methods: Patients with cancers of the urotheliu m who had no prior chemotherapy (prior adjuvant chemotherapy > 6 month s allowed) were eligible for treatment. Eligibility requirements were performance status of 2 or less, creatinine level less than 2.0 mg/dL, granulocyte count (AGC) 1,500/mu L or greater, platelet count 100,000 /mu L or greater, and total bilirubin level less than 1.5 mg/dL. Pacli taxel 200 mg/m(2) followed by carboplatin (area under the curve [AUC] 5, Calvert formula) were administered every 21 days. Patients were eva luated for toxicity weekly and assessed for response every 6 weeks. Re sults: Thirty-six patients were entered onto the study and 35 patients were assessable for response. A total of 184 cycles were administered (median, six cycles per patient). Nine patients required one dose red uction, and seven patients required two dose reductions for a nadir AG C less than 500/mu L, with only one episode of febrile neutropenia and sepsis. Myalgias and arthralgias of grades 1 to 2 occurred in 16 pati ents and usually lasted 2 to 3 days after treatment. There were no tre atment delays because of toxicity. There were 18 responses; seven comp lete responses (CRs) and 11 partial responses (PRs) (response rate 51. 5%; 95% confidence interval, 35 to 68). Median response durations for CR and PR were 6 and 4 months, respectively. Overall median survival w as 9.5 months. Conclusion: The combination of paclitaxel and carboplat in is an active and well-tolerated regimen for the treatment of advanc ed urothelial carcinoma. Because of the modest toxicity of this combin ation, paclitaxel and carboplatin should be considered for addition to other agents with activity in urothelial carcinomas.