Phase II Trial of Subcutaneous Interleukin-2, Subcutaneous Interferon-α, 5-Fluorouracil and Cis-retinoic Acid in the Treatment of Renal Cell Carcinoma: Final Results of Cancer Biotherapy Research Group 94-10

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Abstract
Background: The treatment of metastatic renal cell cancer remains unsatisfactory despite encouraging results with biotherapy. Pilot studies from other investigators have suggested that combining cis-retinoic acid and 5-fluorouracil (5FU) with interleukin-2 (IL-2) and interferon-alpha (IFN) may improve outcomes for such patients. Methods: Eligible patients had metastatic renal cell cancer, were in good medical condition, and had not been treated previously with more than two of the study agents. A 56-day treatment cycle consisted of: interferon-α2a 3.0 μ/m2 s.c. Monday, Wednesday, and Friday weeks 1-8, interleukin-2 11 μ/m2 s.c. Tuesday, Thursday and Saturday of weeks 1-4, cis-retinoic acid 1 mg/kg po daily weeks 1-8, and 5-FU 750 mg/m2 IV weekly during weeks 5-8. Patients were evaluated for tumor response every 8 weeks, and in the absence of tumor progression, patients could receive treatment for up to one year. Survival was determined from the first date of treatment. Results: The 58 renal cell carcinoma patients included 41 men and 17 women, with a median age of 57 years with a range of 28-85 who were enrolled between October 1994 and July 1997. Thirty-seven percent were asymptomatic when treatment was initiated. Sites of disease at study entry included 62% lung, 34% bone, 31% lymph node, 22% kidney, 16% liver and 10% adrenal. There were only three patients with significant tumor responses (one complete, two partial) for a response rate of 5% (0-11% 95% CI) based on intent-to-treat analysis, and 6% (0-12%, 95% CI) for the 53 patients who were evaluable for response. The response rate among evaluable nephrectomized patients who had received no prior radiation or systemic treatment was 3/25 (12%). The median failure-free survival was 2.8 months; median overall survival was 10.9 months. The 1-year survival rate was 50% and 2-year survival rate was 33%. The most frequent toxicities were fatigue-81% (26% grade 3 or 4), nausea/vomiting-59%, and leukopenia/neutropenia 57% (16% grade 3 or 4). Conclusion: Despite a disappointing objective response rate, survival in these patients who were treated entirely as outpatients was similar to that seen in our earlier trials of inpatient, intermediate dose continuous infusion IL-2-based therapy.