RENAL-CELL CARCINOMA - TREATMENT WITH RECOMBINANT INTERLEUKIN-2 PLUS BETA-INTERFERON

Preclinical data have demonstrated synergy between interleukin-2 (IL-2) and beta-interferon (IFN-β) in stimulating natural-killer (NK) cell activity and in increasing expression of IL-2 receptors. Based on results of a phase I trial, a combination of IL-2 and IFN-β was administered three times weekly by intravenous (IV) bolus injection with 5 x 106 Cetus U/m2 of IL-2 and 6 x 106 U/m2 of IFN-β to 24 patients with advanced renal cell carcinoma (RCC). Of 22 assessable patients there were six (27%) objective responses including one complete remission (CR) and five partial responses (PRs). There were three minor responses (MRs), 11 stable disease (SD), and two progressive disease (PD). Two of the objective responses have continued for almost 2 years. Response sites include lymph nodes, lungs, and bone. Toxicities requiring dose reduction include arthralgia, weight loss, fatigue, decreased performance status, depression, and hypotension. Five of 10 patients who had a prior nephrectomy without local recurrence achieved an objective response as compared with only one of 12 without a prior nephrectomy or with a local recurrence (P = .04). Mean peak lymphokine-activated killer (LAK) cell activity of the objective responders was 88 lytic units (LU) as compared with 4 LU in the nonresponders (P = .01). Mean peak NK cell activity was 288 LU in the objective responders as compared with 100 LU in the nonresponders (P = .10). Therefore, there appears to be a positive correlation between response and in vivo induction of LAK cell activity and between response and prior nephrectomy with no local recurrence. These results, which compare favorably to studies using higher doses of IL-2 alone or in combination with ex vivo activated LAK cells, were achieved using a regimen that is well tolerated in the outpatient setting.