A RANDOMIZED STUDY OF CHEMOTHERAPY WITH CISPLATIN PLUS ETOPOSIDE VERSUS CHEMOENDOCRINE THERAPY WITH CISPLATIN, ETOPOSIDE AND THE PINEAL HORMONE MELATONIN AS A FIRST-LINE TREATMENT OF ADVANCED NONSMALL CELL LUNG-CANCER PATIENTS IN A POOR CLINICAL STATE

Recent studies suggest that the pineal hormone melatonin may reduce ch emotherapy-induced immune and bone marrow damage, In addition, melaton in may exert potential oncostatic effects either by stimulating host a nticancer immune defenses or by inhibiting tumor growth factor product ion. On this basis, we have performed a randomized study of chemothera py alone vs. chemotherapy plus melatonin in advanced nonsmall cell lun g cancer patients (NSCLC) with poor clinical status. The study include d 70 consecutive advanced NSCLC patients who were randomized to receiv e chemotherapy alone with cisplatin (20 mg/m(2)/day i.v. for 3 days) a nd etoposide (100 mg/m(2)/day i.v. for 3 days) or chemotherapy plus me latonin (20 mg/day orally in the evening). Cycles were repeated at 21- day intervals, Clinical response and toxicity were evaluated according to World Health Organization criteria. A complete response (CR) was a chieved in 1/34 patients concomitantly treated with melatonin and in n one of the patients receiving chemotherapy alone. Partial response (PR ) occurred in 10/34 and in 6/36 patients treated with or without melat onin, respectively. Thus, the tumor response rate was higher in patien ts receiving melatonin (11/34 vs. 6/35), without, however, statistical ly significant differences. The percent of 1-year survival was signifi cantly higher in patients treated with melatonin plus chemotherapy tha n in those who received chemotherapy alone (15/34 vs. 7/36, P < 0.05). Finally, chemotherapy was well tolerated in patients receiving melato nin, and in particular the frequency of myelosuppression, neuropathy, and cachexia was significantly lower in the melatonin group. This stud y shows that the concomitant administration of melatonin may improve t he efficacy of chemotherapy, mainly in terms of survival time, and red uce chemotherapeutic toxicity in advanced NSCLC, at least in patients in poor clinical condition.