Sequential therapy with gemcitabine and carboplatin followed by paclitaxel as first line treatment for advanced urothelial cancer

Abstract

Objective: Gemcitabine and platinum-based compounds represent the new standard combi-nation therapy for bladder cancer. In this study, we evaluate the efficacy and safety of gem-citabine and carboplatin followed sequentially by paclitaxel in 27 patients with advanced transitional cell carcinoma. Methods: This phase II multicentre study was based on the doublet gemcitabine 800 mg/m2 and carboplatin area under the concentration-time curve 2 on days 1 and 8 every 21 days for 4 cycles, followed sequentially by paclitaxel 60 mg/m2/w for 12 consecutive weeks. The disease was assessed after each sequence. Results: Primary tumor was localized in the bladder and renal pelvis in 25 and 2 patients, re-spectively. Twenty patients completed all 4 cycles of the gemcitabine and carboplatin se-quence. Mean number of cycles was 3.5 (range 1 to 4). Toxicities were mainly hematologic, including Grade 3 neutropenia and anemia in 3 patients. Objective response was noted in 11 pts (40.7%), including 1 complete response (CR) and 10 partial responses (PR). Three patients had stable disease and 11 progressed. Among the 20 patients, 14 received the second se-quence. Mean number of paclitaxel injections was 7 (range 2 to 12). Toxicities were limited to diarrhea and neurotoxicity in 1 patient each. Objective response was documented in 6 pa-tients (30%) (3 CR and 3 PR), including the improvement of PR into CR in 2 patients. Median duration of response was 6 months. After a median follow-up of 7 months, 21 patients died and 6 remained alive, including 2 who maintained CR and 1 PR. Sixteen patients had locally advanced disease and 11 had metastatic disease, better prognostic was noticed with patients with locally advanced disease. Conclusion: the sequential approach of treatment for advanced urothelial cancer using gem-citabine and carboplatine followed by paclitaxel seems to be a safer alternative to the com-bined triplet, but due to the limited number of patients this study failed to improve outcome. Further investigations with larger population are required. © Ivyspring International Publisher.