PHASE-I STUDY OF SUBCUTANEOUSLY ADMINISTERED INTERLEUKIN-2 IN COMBINATION WITH INTERFERON ALFA-2A IN PATIENTS WITH ADVANCED CANCER

Purpose: Although high-dose interleukin-2 (IL-2) can produce durable r emissions in a subset of responding patients with renal cell carcinoma (RCC), this occurs in the setting of significant toxicity, The purpos e of this study is to define the maximum-tolerated dosage (MTD) of IL- 2 and interferon alfa-2a (IFN alpha-2a) that can be administered chron ically on an outpatient basis. Patients and Methods: Fifty-three patie nts with advanced cancer of variable histology with good prognostic fe atures were treated in six cohorts. Patients in cohorts one through fi ve received IL-2 (1.5 or 3.0 x 10(6) million units (mU)/m(2)) Monday t hrough Friday and IFN alpha-2a (1.5 or 3 x 10(6) mU/m(2)) daily for a 4-week cycle. In cohort six, IFN alpha-2a was given three times a week . Immunologic monitoring, including serum levels of soluble IL-2 recep tor (sIL-2R) and neopterin, flow cytometry, and natural killer cell (N K) activity, were measured. Patients were evaluated for toxicity, resp onse, and survival. Results: Almost all patients developed grade I/II toxicities commonly associated with cytokine therapy. Symptoms were mo st severe with the first treatment of each week. Dose-limiting toxicit ies included grade III fatigue, hypotension, and creatinine elevations . The MTD was 1.5 mU/m(2) daily x 5 given subcutaneously repeated week ly for IL-2 and 1.5 mU/m(2) daily subcutaneously (dose level 3) for IF N. Six of 25 assessable patients with RCC (24%) achieved a partial res ponse (PR), including four of eight patients who were previously untre ated. There were no objective responses in patients with other tumors, including 12 melanoma patients. Conclusion: IL-2 and IFN alpha-2a can be given with tolerable toxicities on an outpatient basis and shows s ignificant activity in patients with metastatic RCC.