A RANDOMIZED STUDY OF NEUROIMMUNOTHERAPY WITH LOW-DOSE SUBCUTANEOUS INTERLEUKIN-2 PLUS MELATONIN COMPARED TO SUPPORTIVE CARE ALONE IN PATIENTS WITH UNTREATABLE METASTATIC SOLID TUMOR

Recent advances in our knowledge of psychoneuroimmune interactions inv olved in the control of tumour growth have shown the possibility of ma nipulating host anticancer defences through a neuroimmunotherapeutic s trategy. In particular, our previous studies have demonstrated that th e concomitant administration of the pineal neurohormone melatonin may amplify the antitumour efficacy of interleukin-2 (IL-2) in humans. On this basis, a study was planned to investigate the influence of neuroi mmunotherapy with low-dose IL-2 plus melatonin on survival time and on performance status in untreatable metastatic cancer patients, The stu dy included 100 patients with metastatic solid tumours, for whom no st andard therapy was available, They were randomized to receive IL-2 (3 x 10(6) IU/day subcutaneously for 4 weeks) plus melatonin (40 mg/day o rally) or supportive care alone. Partial tumour regressions were seen in 9/52 (17%) patients treated with the immunotherapy, and in none of the patients treated with supportive care alone. The percentage of sur vival at 1 year was significantly higher in patients treated with IL-2 and melatonin than in those receiving the supportive care alone (21/5 2 versus 5148, P<0.005). Moreover, the performence status improved in 22/52 patients of the immunotherapy group and in only 8/48 patients tr eated with supportive care (P<0.01). This study shows that cancer neur oimmunotherapy with low-dose IL-2 and the pineal hormone melatonin may prolong the survival time and improve the quality of life of patients with metastatic solid tumours who do not respond to conventional ther apies.