Phase II trial of weekly paclitaxel, cisplatin plus infusional high dose 5-fluorouracil and leucovorin for metastatic urothelial carcinoma.

Purpose: Conventional chemotherapy for urothelial carcinoma, such as methotrexate, vinblastine, doxorubicin and cisplatin, is associated with significant toxicity. We have previously reported a low toxicity and yet moderately active regimen containing weekly infusional cisplatin and high dose 5-fluorouracil/leucovorin for advanced urothelial carcinoma. We tested the efficacy and toxicity of adding paclitaxel to that regimen.

Materials And Methods: Between April 2000 and December 2004, 44 patients with a median age of 66 years with metastatic urothelial carcinoma were enrolled. The paclitaxel, cisplatin and high dose 5-fluorouracil/leucovorin regimen consisted of 70 mg/m2 paclitaxel daily as a 1-hour infusion on days 1 and 8, 35 mg/m2 cisplatin daily as a 24-hour infusion on days 2 and 9, 2,000 mg/m2 5-fluorouracil daily and 300 mg/m2 leucovorin daily as a 24-hour infusion on days 2 and 9. The cycles repeated every 21 days. A total of 25 patients (64%) had a creatinine clearance of 35 to 60 ml per minute.

Results: A total of 210 cycles (mean 4.8 per patient) were administered. Of the 40 patients eligible for response evaluation 11 (28%) and 19 (48%) were complete and partial responders with an overall response rate of 75% (95% CI 61 to 89). Median overall and progression-free survival in the whole group was 17.0 (95% CI 13.7 to 20.3) and 8.3 months (95% CI 6.4 to 10.2), respectively. Two-year disease-free survival was 15%. Grade 3 or 4 anemia, leukopenia and thrombocytopenia occurred at 23, 30 and 12 cycles, respectively. Nonhematological toxicity included infection, vomiting and diarrhea, etc. There were 2 treatment related deaths.

Conclusions: Paclitaxel, cisplatin and high dose 5-fluorouracil/leucovorin is an active regimen against metastatic urothelial carcinoma which has an acceptable toxicity profile.