Melatonin plus interleukin-2 is more effective as neuroimmunotherapy than melatonin plus somastatin analogs and bromocriptine as polyneuroendocrine therapy in untreatable advanced solid tumor patients

Melatonin has been proven to have antitumor activity through both endocrine and immunomodulatory effects. Therefore, to further enhance its anticancer property melatonin could be combined either with antitumor cytokines, name ly interleukin (IL)-2 and IL-12, or with other oncostatic neuroactive subst ances, such as somatostatin analogs and dopaminergic agents to inhibit the secretion of potential tumor growth factors, such as somatomedins and prola ctin. The present study was carried out to compare the therapeutic anticanc er efficacy of two different biotherapeutic combinations containing melaton in, combined with the anti-tumor cytokine IL-2 or with the somatostatin ana log octreotide and the long-acting dopaminergic agonist bromocriptine. The study included 100 consecutive patients with untreatable metastatic solid t umor who were randomized to receive melatonin plus low-dose IL-2 (3 million IU/day subcutaneously (s.c.) for 6 days/week for 4 weeks) or melatonin plu s octreotide (1 mg/day s.c.) and bromocriptine (2.5 mg/day orally). Melaton in was given orally at 20 mg/day in the evening to both groups of patients. The objective tumor regression rate obtained with melatonin plus IL-2 was significantly higher than that found in patients treated with melatonin plu s octreotide and bromocriptine (8/52 vs. 0/48, p <0.01). Similarly the perc ent of 1-year survival was significantly higher in patients receiving melat onin plus IL-2. This preliminary study suggests that melatonin is more acti ve as an antitumor agent in human neoplasms in combination with antitumor c ytokines according to a neuroimmunotherapeutic strategy than in combination with other neuroactive oncostatic molecules.