Long-term results of cancer immunotherapy with subcutaneous low-dose interleukin-2 plus melatonin

The pineal gland has been experimentally proven to play a fundamental role in the neuroendocrine regulation of antitumor immunity, and the pineal horm one melatonin has been found to amplify the clinical efficacy of interleuki n (IL)-2 anticancer immunotherapy. Our previous clinical studies have shown that neuroimmunotherapy with IL-2 plus melatonin may enhance I-year surviv al in untreatable advanced solid tumor patients with a life expectancy of l ess than 6 months. This study describes the 3-year survival rate obtained w ith IL-2 plus melatonin in a group of untreatable solid tumor patients with respect to supportive care or IL-2 alone. The study included 120 advanced cancer patients with a life expectancy of less than 6 months, suffering fro m nonsmall cell lung cancer or gastrointestinal tract neplasms, and for who m no other effective standard therapy was available. Patients were randomiz ed to receive supportive care only, IL-2 alone (3 million IU/day subcutaneo usly in the evening for 6 days/week for 4 weeks) or IL-2 plus melatonin (40 mg/day orally in the evening in association with IL-2, or 20 mg/day during the intervals between IL-2 injections). The tumor regression rate obtained in patients treated with IL-2 and melatonin was significantly higher with respect to that seen in both groups of patients treated with supportive car e or IL-2 alone. In the same way, the percentage of 3-year survival was sig nificantly higher in patients treated with IL-2 and melatonin than in the o ther groups of patients. These results confirm that neuroimmunotherapy with IL-2 and melatonin may be considered a new effective therapy of advanced h uman neoplasms, capable of prolonging the survival time in patients for who m no standard therapy is available, including those affected by neoplasms w hich are generally resistant to IL-2 alone.