Subcutaneous interleukin-2 plus interferon alfa-2a in metastatic renal cancer: an outpatient multicenter trial.

PURPOSE: A prospective multicenter phase II trial was undertaken to define the activity of a low-dose subcutaneous regimen of interleukin-2 (IL-2) and interferon alfa-2a (IFN) in patients with metastatic renal cancer. PATIENTS AND METHODS: Between December 1990 and October 1991, 42 patients with metastatic renal cancer who had received no prior immunotherapy were treated with IL-2 (4 x 10(6) U) days 1 through 4 and IFN (9 x 10(6) U) day 1 and 4 each week of a 4-week treatment course followed by a 2-week rest period. Maximum duration of therapy was 1 year. Concomitant therapy with acetaminophen, diphenhydramine, and indomethacin was recommended. Treatment was administered on an outpatient basis. RESULTS: With a median follow-up duration of 18 months, responses occurred in five of 42 patients (12%; 95% confidence interval [Cl], 2% to 22%). One pathologic complete remission, one surgical complete remission, and three partial remissions occurred. Toxicity was modest, with a symptom complex of rash, fever, anorexia, fatigue, mild weight loss, lymphocytosis, and eosinophilia occurring in 85% to 90% of patients. Renal dysfunction (creatinine > 2 mg/dL) occurred in 19% of patients, while three patients (7%) refused further IL-2 and IFN. No toxic deaths occurred. The median survival duration was 14.5 months. CONCLUSION: This outpatient low-dose subcutaneous regimen induced mild toxicity, a modest response rate, and an excellent median survival duration in previously untreated patients. Phase III trials are now needed to compare IL-2 plus IFN with IL-2 alone or to various IL-2/IFN regimens. However, the major task is to identify unique new agents with activity in renal cancer.