IMMUNOENDOCRINE THERAPY WITH INTERLEUKIN-2 (IL-2) AND MEDROXYPROGESTERONE ACETATE (MPA) - A RANDOMIZED STUDY WITH OR WITHOUT MPA IN METASTATIC RENAL-CANCER PATIENTS DURING IL-2 MAINTENANCE TREATMENT AFTER RESPONSE OR STABLE DISEASE TO IL-2 SUBCUTANEOUS THERAPY

Aims and Background: It is known that interleukin-2 (IL-2) activated cytotoxic lymphocytes require a cell-cell contact to exert their anticancer action. Therefore, the pronounced fibrosis that generally characterizes the neoplastic mass could counteract the action of cytotoxic lymphocytes. Some preliminary studies have shown that progesterone and its analogs may inhibit fibroblast proliferation. On the basis of such evidence, we have designed a clinical study with or without the progestational agent medroxyprogesterone acetate (MPA) in metastatic renal cancer patients in maintenance therapy with IL-2 following response or stable disease (SD) after two cycles of IL-2 subcutaneous immunotherapy, in an attempt to evaluate the influence of MPA on free-from progression (FPP) period. Methods: The study included 30 consecutive patients who were randomized to receive IL-2 alone (3 mllion IU twice/day for 5 days/month subcutaneously) or IL-2 plus low-dose mg orally one day/week) without interruption until disease progression. Results: A FPP period longer than 1 year was obtained in 8/14 patients treated with IL-2 plus MPA and in only 3/16 patients treated with IL-2 alone. The difference was statistically significant. On the contrary, no significant difference was seen in the mean number of lymphocytes and eosinophils, which was evaluated monthly. Finally, no hyperglycemic or thromboembolic complications occurred in patients concomitantly treated with MPA. Conclusions: This preliminary study would suggest that the concomitant administration of low-dose MPA may prolonge the FFP period in metastatic renal cancer patients under maintenance therapy with IL-2. A longer follow-up will be required to evaluate the influence of MPA on overall survival.