RECOMBINANT HUMAN INTERLEUKIN-2, RECOMBINANT HUMAN INTERFERON ALPHA-2A, OR BOTH IN METASTATIC RENAL-CELL CARCINOMA

Background Recombinant human interleukin-2 (aldesleukin) and recombina nt human interferon alfa can induce notable tumor regression in a limi ted number of patients with metastatic renal-cell carcinoma. We conduc ted a multicenter, randomized trial to determine the effect of each cy tokine independently and in combination, and to identify patients who are best suited for this treatment. Methods Four hundred twenty-five p atients with metastatic renal-cell carcinoma were randomly assigned to receive either a continuous intravenous infusion of interleukin-2, su bcutaneous injections of interferon alfa-2a, or both. The main outcome measure was the response rate; secondary outcomes were the rates of e vent-free and overall survival. Predictive factors for response and ra pid progression were identified by multivariate analysis. Results Resp onse rates were 6.5 percent, 7.5 percent, and 18.6 percent (P<0.01) fo r the groups receiving interleukin-2, interferon alfa-2a, and interleu kin-2 plus interferon alfa-2a, respectively. At one year, the event-fr ee survival rates were 15 percent, 12 percent, and 20 percent, respect ively (P=0.01). There was no significant difference in overall surviva l among the three groups. Toxic effects of therapy were more common in patients receiving interleukin-2 than in those receiving interferon a lfa-2a. Response to treatment was associated with having metastasis to a single organ and with receiving the combined treatment. The probabi lity of rapid progression of disease was at least 70 percent for patie nts with at least two metastatic sites, liver metastases, and a period of less than one year between the diagnosis of the primary tumor and the appearance of metastases. Conclusions Cytokines are active in a fe w patients with metastatic renal-cell carcinoma. The higher response r ate and longer event-free survival obtained with a combination of cyto kines must be balanced against the toxicity of such treatment. (C)1998 , Massachusetts Medical Society.