A Randomized Study of High-Dose Pineal Hormone Melatonin Alone Versus High-Dose Melatonin Plus Low-Dose Angiotensin-(1-7) in Untreatable Advanced Cancer Patients

Abstract

The recent advances in the knowledge of the neuroendocrine control of the immune system and cancer growth have demonstrated the existence of several anticancer natural molecules in the human body, the most promising of them are the pineal hormone melatonin (MLT) and the enzymatic product of ACE2, the angiotensin 1-7 (Ang 1-7). Both MLT and Ang 1-7 have no toxicity, and they exert their antitumor action through several mechanisms, including inhibition of cancer cell proliferation and angiogenesis, and stimulation of the anticancer immunity. Previous preliminary clinical studies had already shown that high-dose MLT may induce a disease control in advanced cancer patients eligible for the only palliative therapy. The present study was performed to evaluate whether the concomitant administration of Ang 1-7 may furtherly increase the antitumor efficacy of MLT in untreatable cancer patients suffering from various tumour histotypes. The study included 70 consecutive advanced untreatable cancer patients, who were randomized to receive the only best supportive care, high-dose MLT (100 mg/day in the dark period), or MLT plus Ang 1-7 (0.5 mg twice/day). The percentage of disease control (DC), including stable disease and tumor regressions, achieved in patients treated by MLT plus Ang 1-7 was significantly higher with respect to those obtained in patients treated with MLT alone (P<0.05) or with the only supportive care (P<0.001). No toxicity was seen under therapy of MLT plus Ang 1-7. In contrast, most patients experienced mood improvement, a diminished anxiety, and a relief of asthenia, which was more evident in patients concomitantly treated by MLT and Ang 1-7.