Phase II trial of subcutaneous interferon followed by intravenous hybrid bolus/continuous infusion interleukin-2 in the treatment of renal cell carcinoma: final results of Cancer Biotherapy Research Group 95-09.

OBJECTIVE: We conducted a phase II trial in metastatic renal cell cancer of outpatient subcutaneous (s.c.) interferon-alpha2b (IFN), followed by an inpatient hybrid schedule of bolus and continuous interleukin-2 (IL- 2). METHODS: Treatment consisted of monthly IFN 10 MU/m(2) s.c. for 4 consecutive days, followed by 36 MIU/m(2) bolus IL-2, then 72-hour continuous intravenous (i.v.) infusion of 18 MIU/m(2) IL-2 per day. Between May 1997 and June 2000, 25 men and 11 women enrolled, with a median age of 57 years (range, 42-77), including 9 patients over 65. Prior treatment included nephrectomy (31), radiation (8), biotherapy (7), and chemotherapy (4). Sites of disease included 26 lung, 13 lymph node, 9 bone, 8 liver, 4 kidney, and 4 adrenal locations. Patients received an average of 3.1 treatment cycles (range, 1-6). RESULTS: There was 1 complete and 3 partial responses, for a response rate of 11% (3% to 27%; 95% confidence interval [CI]); 40% had stable disease. Median failure-free survival was 2.5 months; median overall survival was 15.0 months. The 1-, 2-, and 5-year survival rates were 53%, 30%, and 12%, respectively. Only 8 patients required a reduction in IL-2 dose. The most frequent grade 3 or 4 toxicities were 11% fatigue, 9% renal insufficiency, and 7% hypotension. CONCLUSIONS: Response and survival rates were similar to those seen in other multicenter trials using inpatient high-dose IL-2.

Phase II trial of subcutaneous interleukin-2, subcutaneous interferon-alpha, 5-fluorouracil and cis-retinoic acid in the treatment of renal cell carcinoma: final results of cancer biotherapy research group 94-10.

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-alpha 2a 3.0 mu/m2 s.c. Monday, Wednesday, and Friday weeks 1-8, interleukin-2 11 mu/m2 s.c. Tuesday, Thursday and Saturday of weeks 1-4, cis-retinoic acid 1 mg/kg p.o. daily weeks 1-8, and 5-FU 750 mg/m2 i.v. 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.