J Cancer 2012; 3:362-368. doi:10.7150/jca.4224
Sequential Therapy with Gemcitabine and Carboplatin Followed by Paclitaxel as First Line Treatment for Advanced Urothelial Cancer
1. Cancer Research Group (CRG) Collaborative Group, Hotel-Dieu de France University Hospital;
2. American University of Beirut Medical Center, Beirut, Lebanon.
Kattan JG, Boutros CY, Farhat FS, Chahine GY, Musallam KM, Ghosn MG. Sequential Therapy with Gemcitabine and Carboplatin Followed by Paclitaxel as First Line Treatment for Advanced Urothelial Cancer. J Cancer 2012; 3:362-368. doi:10.7150/jca.4224. Available from http://www.jcancer.org/v03p0362.htm
Objective: Gemcitabine and platinum-based compounds represent the new standard combination therapy for bladder cancer. In this study, we evaluate the efficacy and safety of gemcitabine 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, respectively. Twenty patients completed all 4 cycles of the gemcitabine and carboplatin sequence. 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 sequence. 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 patients (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 gemcitabine and carboplatine followed by paclitaxel seems to be a safer alternative to the combined triplet, but due to the limited number of patients this study failed to improve outcome. Further investigations with larger population are required.
Keywords: bladder cancer, gemcitabine, carboplatin, paclitaxel, sequential therapy.