A phase II trial of weekly intravenous gemcitabine and cisplatin with continuous infusion fluorouracil in patients with metastatic renal cell carcinoma

Background: We reported previously that the combination of gemcitabine and continuous infusion fluorouracil (5-FU) has activity in renal cell carcinoma [1]. Based upon in vitro synergy of gemcitabine/cisplatin and 5-FU/cisplatin, we hypothesized that the addition of cisplatin could improve the objective response rate of gemcitabine and 5-FU with manageable toxicity. Patients and methods: Twenty-one patients with metastatic renal cell carcinoma (RCC) and a Cancer and Leukemia Group B performance status of 0 to 2 were enrolled. Ten had received prior systemic therapy. Treatment consisted of gemcitabine 600 mg/m(2) and cisplatin 20 mg/m(2) on days 1, 8 and 15 of each 28-day cycle. Continuous infusion 5-FU was given from day 1 to day 21. Results: No complete responses and one partial response were observed for an objective response rate of 5% (95% confidence interval 0% to 24%). Two minor responses (25% to 50% regression) were also observed. The median overall survival was 10 months with 35% of patients surviving at I year. Grade 3-4 myelosuppression (mostly thrombocytopenia) occurred in nine (43%) patients. Nausea/vomiting and neuropathy were dose-limiting in an additional five patients, Only 51% of treatment cycles were delivered on time and without dose reduction. Conclusions: The addition of cisplatin to gemcitabine and 5-FU did not improve the objective response rate of gemcitabine and 5-FU alone and added to the toxicity. Due to the cumulative toxicity, further trials with this cisplatin-containing regimen in RCC are not indicated.