A RANDOMIZED STUDY OF IMMUNOTHERAPY WITH LOW-DOSE SUBCUTANEOUS INTERLEUKIN-2 PLUS MELATONIN VS CHEMOTHERAPY WITH CISPLATIN AND ETOPOSIDE CISPLATIN AND ETOPOSIDE AS FIRST-LINE

Aims and Background: The theraputic role of chemotherapy in advanced n on-small cell lung cancer (NSCLC) is controversial because of its pote ntially detrimental action on host anticancer defenses. On the contrar y, IL-2 would seem to prolong survival time by improving the immune st atus, even though it is generally less effective in determining tumor regression in NSCLC. Our previous studies have suggested the possibili ty of increasing tumor sensitivity to IL-2 by concomitant administrati on of immunomodulating neurohormones, such as the pineal hormone melat onin (MLT). On this basis, a study was carried out to evaluate the eff icacy of immunotherapy with low-dose IL-2 plus MLT versus chemotherapy in advanced NSCLC. Methods: The study included 60 patients with local ly advanced or metastatic NSCLC, who were randomized to receive immuno therapy or chemotherapy. The immunotherapy consisted of IL-2 (3 millio n IU/day subcutaneously for 6 days/week for 4 weeks) and MLT (40 mg/da y orally every day, starting 7 days before IL-2); in nonprogressing pa tients, a second cycle was repeated after a al-day rest period, then t hey underwent a maintenance period consisting of one week of therapy e very month until progression. Chemotherapy consisted of cisplatin (20 mg/m(2)) and etoposide (100 mg/m(2))/day intravenously for 3 days; cyc les of chemotherapy were repeated every 21 days until progression. Res ults: No complete response was obtained. A partial response was achiev ed in 7/29 patients treated with chemotherapy and in 6/31 patients rec eiving chemotherapy. The difference was not significant. In contrast, the mean progression-free period and the percentage survival at 1 year was significantly higher in patients treated with immunotherapy than in those treated with chemotherapy. Toxicity was substantially lower i n patients receiving immunotherapy than in those given chemotherapy. C onclusions: This randomized study showed that immunotherapy with low-d ose IL-2 plus MLT is a better tolerated and more effective therapy in terms of survival time than chemotherapy containing cisplatin in patie nts affected by advanced NSCLC.