CLINICAL AND IMMUNOMODULATORY EFFECTS OF REPETITIVE 2-DAY CYCLES OF HIGH-DOSE CONTINUOUS-INFUSION IL-2

High-dose interleukin-2 (IL-2) treatment has demonstrated promising an titumour activity in renal cell carcinoma (RCC) and malignant melanoma (MM) and has been shown to induce broad .immunological effects. The o ptimal IL-2 Bose and schedule, however, still remain to be defined. We studied a treatment protocol consisting of five repetitive cycles of high-dose recombinant (rh) IL-2 (24 x 10(6) U/m(2)/day) administered w eekly on two consecutive days by continuous intravenous infusion. 17/1 9 were RCC patients, 2 of whom responded with a complete remission (CR ) and 3 with a partial response (PR) (CR + PR: 29%; median response du ration of 11.5+ months (range: 3-14 months)). IL-2 induced a pronounce d increase of lymphocytes and pro-inflammatory cytokines IL-8, IL-5, g amma-IFN, TNF-alpha and TNF-beta (p < 0.05) that peaked in cycle 3. Wi th subsequent therapy, serum levels of these cytokines, NK, T cells an d eosinophils decreased, whereas serum IL-10 levels progressively incr eased with maximum levels achieved after the fifth week of treatment, suggesting that it may be involved in dampening the inflammatory respo nse induced by IL-2. Absolute numbers of activated T cells and NK cell s remained elevated as compared to baseline for at least 4 weeks after treatment cessation. Based on these observations, future scheduling o f IL-2 will be done at 3 weekly 2-day cycles separated by a week 4 tre atment-free interval in order to increase further the 29% objective re sponse rate achieved in this study. (C) 1997 Elsevier Science Ltd.