Phase II trial of 5-fluorouracil, interferon-α and continuous infusion interleukin-2 for patients with metastatic renal cell carcinoma

BACKGROUND. This study was designed to evaluate the efficacy and toxicity of the combination of 5-fluorouracil, interferon-α, and interleukin-2 for patients with metastatic renal cell carcinoma. METHODS. Previously untreated patients with a Zubrod performance status of ≤2; adequate cardiac, pulmonary, and renal function; and absence of brain metastases were eligible. One course of therapy was 28 days, 5-fluorouracil was administered at a dose of 600 mg/m²/day as a continuous infusions on Days 1-5. Interleukin-2 also was administered as a continuous infusion on Days 1-5 at a dose of 2 million Roche U/m²/day. Interferon-α was given as a daily subcutaneous injection of 4 million U/m²/day. RESULTS. Fifty-five patients were enrolled in the trial and 52 were evaluable for response. All patients experienced fever and flu-like symptoms. Grade 3 or 4 nonhematologic toxic effects included hypertension (48%), dermatitis (12%), stomatitis (11%), and altered mental status (9%). There was one toxic death. Four complete responses and 12 partial responses were observed for a total response rate of 31% (95% confidence interval, 18-46%). The survival of responding patients was significantly better than that of nonresponding patients. The improvement in survival was even more significant when comparing patients with at least stable disease with those who progressed thorough treatment. CONCLUSIONS. The three-drug combination described in this study demonstrates activity. However, it appears to be more toxic than other regimens with similar response rates and cannot be recommended for standard practice. Changing the interleukin-2 route to subcutaneous administration may permit more continuous administration with less toxic effects.