A phase II trial of intravenous gemcitabine and 5-fluorouracil with subcutaneous interleukin-2 and interferon-α in patients with metastatic renal cell carcinoma

BACKGROUND. The objective of this study was to determine the response rate and toxicity of gemcitabine and continuous-infusion 5-fluorouracil (5-FU) in combination with subcutaneous interleukin-2 (IL2) and interferon-α (IFNA) in patients with metastatic renal cell carcinoma. METHODS. Forty-one patients were treated with gemcitabine 600 mg/m² on Days 1, 8, and 15 and continuous-infusion 5-FU on Days 1-21. The dose of 5-FU was 200 mg/m² per day for the initial 8 patients but was reduced to 150 mg/m² per day for all remaining patients due to toxicity. Starting on Day 15, IL2 and IFNA were administered for 4 weeks. IL2 was administered at a dose of 11 x 10⁶ IU subcutaneously (sc) 4 days per week and IFNA was administered at a dose of 10.0 x 10⁶ IU sc 2 days per week. RESULTS. Of 41 patients enrolled in the study, there was 1 complete response (CR), and there were 5 partial responses (PR), for an overall response rate of 14.6% (90% confidence interval [90%CI], 6.6-26.9%). The median time to disease progression was 6.6 months (90%CI, 3.9-7.5 months), and the median overall survival was 20.6 months (90%CI, 9.6-23.3 months). Toxicity was moderate to severe, with fatigue, fever, anorexia, or nausea experienced by 75-90% of patients. Mucositis and neutropenia, likely due to the gemcitabine and 5-FU, were experienced by a majority of patients. CONCLUSIONS. The addition of gemcitabine and 5-FU to subcutaneous IL2 and IFNA results in a similar response rate to what was observed in previous studies of IL2-based therapy. The toxicity of this four-drug combination is significant, and the regimen is not recommended for further development.