Interleukin-2, interferon-alpha and interleukin-2 plus interferon-alpha inrenal cell carcinoma. A randomized phase II trial

Background: The purpose of the present study was to investigate the therape utic effectiveness of interleukin-2 (IL-2) and interferon (IFN), either alo ne or in combination, in comparable groups of patients affected by advanced renal cell carcinoma Patients and methods: In order to limit selection bia ses, treatment was allocated on a random basis, Patients randomized to IL-2 alone were scheduled to receive eight rIL-2 24-hour i.v. infusion cycles, days 1 to 4, at a daily dose of 18 x 10(6) IU/m(2) for a total of 25 weeks. Patients randomized to IFN alone were scheduled to receive rIFN-alpha at a daily dose of 6 x 10(6) IU/m(2), days 1, 3 and 5, every week for a total o f 52 weeks, Patients randomized to the combination of IFN and IL-2 were giv en the same drugs at the same daily doses for a total of 24 weeks. Drug dos e was modified according to toxicity, Results: Twenty-three percent (95% CI : +/- 17.5) of patients treated with IL-2 alone showed an objective respons e to treatment (9% CR), The corresponding figures in patients treated with IFN alone or IFN plus IL-2 were 9% (95% CI: +/- 11.9) and 9% (95% CI: +/- 1 1.9), respectively. Complete responses were observed only in patients treat ed with IL-2, The median duration of response in the IL-2 arm was 18 months (range, 9.5-24). The duration of the two responses achieved by IFN alone w as seven and nine months, respectively. The corresponding figures in the tw o patients responding to the combination of IFN with IL-2 were 19 and 27 mo nths, respectively. Total IL-2 dose appeared to be a major predictor of res ponse. Only a minority of patients experienced grade 3-4 toxicity, the inci dence being higher In those treated with IL-2 or IL-2 plus IFN, Conclusions : Neither IFN nor IL-2 or the combination of the two appear to be very acti ve in patients with advanced RCC, even when trial entry was restricted to p atients with relatively indolent disease. This stresses the need for the de velopment of new approaches.