Cytokines in metastatic renal cell carcinoma: Is it useful to switch to interleukin-2 or interferon after failure of a first treatment?

Purpose: Interleukin-2 (IL-2) and interferon alfa-2a (IFN alpha 2a) have so me antitumor activity in metastatic renal cell carcinoma either alone or in combination. To determine whether either of these cytokines might be effic ient after failure of the other, we analyzed a series of patients treated w ith either IL-2 or IFN alpha 2a as second-line treatment after failure of t he other cytokine, Patients and Methods: We recently performed a large multicenter study to de termine the respective efficacy of IL-2, IFNa2a, or combined treatment in r enal cell carcinoma. In this study, patients who progressed on the single-a rm treatment could receive the other cytokine in a cross-over trial. IL-2 w as administered as a continuous intravenous infusion for 5 days (18 x 10(6) IU/m(2)/d), and IFN alpha 2a was administered three times weekly at 18 x 1 0(6) IU. Results: A total of 113 patients with progressive disease after first-line treatment received either IFN alpha 2a (n = 48) or IL-2 (n = 65). Toxicity during second-line treatment was similar to that observed during first-line treatment, Only four partial responses were observed (one with lFN alpha 2 a and three with IL-2). All partial responders had a performance status of 0 and lung metastases. Moreover, three of these four patients had stable di sease or had responded to first-sine therapy. Only one patient with confirm ed disease progression after receiving IL-2 subsequently responded to IFN a lpha 2a. Conclusion: Cross-over after failure of IL-2 or lFN alpha 2a is poorly effi cient in metastatic renal cell carcinoma, especially when progression has b een clearly documented. (C) 1999 by American Society of Clinical Oncology.