Abstract
We investigated the biological response of 73 patients with metastatic renal‐cell carcinoma (MRCC) treated by repetitive weekly cycles of high‐dose interleukin 2 (IL‐2) (protocol 1, 40 patients) or IL‐2 plus interferon‐gamma (IFN‐γ) (protocol 2, 33 patients). The objectives of this study were (i) to evaluate the effects of this IL‐2 administration schedule on biological response, (ii) to compare the effects of IL‐2 alone with those of IL‐2 plus IFN‐γ, (iii) to search for any correlation between certain biological marker values and the clinical response to treatment. Mean CD56^+^ lymphocyte counts (i. e., NK cells) were significantly higher than those of CD3^+^ cells in the 2 protocols and a subpopulation of CD56^bright^ cells in protocol I was found to be preferentially expanded in vivo. Cytotoxic activity against K562 and Daudi cell lines as well as TNF‐α and sTNF‐αR (but not IL‐6) significantly increased following treatment. Comparison of the data obtained from patients treated with IL‐2 alone vs. IL‐2 plus IFN‐γ did not show any significant changes except for eosinophilia (higher in protocol I). Therefore, addition of IFN‐γ did not affect either lymphocyte distribution or non‐MHC‐restricted cytotoxicity in vivo. No difference in cell subpopulation or cytotoxicity was detected between responders and non‐responders. Pre‐treatment sTNF‐αR concentration, in contrast to IL‐6 and TNF‐α, was significantly higher in progressive than in stable and responder groups, suggesting that this parameter may be predictive of the clinical response. © 1994 Wiley‐Liss, Inc.