How To Biologically Modulate Cancer Chemotherapy: A Randomized Study With Chemotherapy Alone Or Chemotherapy Plus A Neuroendocrine Regimen With High-Dose Melatonin And Cannabinol Vs Melatonin, Cannabinol And Low-Dose Angiotensin 1-7 In Locally Advanced Or Metastatic Cancer Patients

Lissoni P, Rovelli F, Valentini A, Alejandramonzon A, Messina G, Porro G, Carassai P, Di Fede G, Ceppodomo D and Cardinali D

Published on: 2022-02-28

Abstract

In addition to its cytotoxic effects, cancer chemotherapy (CT) has also appeared to modulate the antitumor immunity in both positive and negative manner, depending on its influence on the cytokine network. Moreover, it has been proven that the cytokine network is physiologically under a neuroendocrine regulation, and it has been demonstrated the existence of a fundamental anticancer anti-inflammatory axis constituted of the pineal gland, the endocannabinoid system, and ACE2-angiotensin 1-7 (Ang 1-7). On these bases, a study was planned to evaluate the influence of a concomitant administration of the pineal hormone melatonin (MLT), the cannabinoid agent cannabidiol (CBD), and Ang 1-7 on the efficacy and safety of cancer CT. The study included 100 advanced cancer patients suffering from the most common tumor histotypes, who were randomized to receive CT alone, or CT in association with a concomitant oral administration of high-dose MLT (100 mg/day in the night) and CBD (10 mg twice/day) alone, or MLT and CBD plus Ang 1-7 (0.5 mg/day in the morning). The percentage of both objective tumor regressions and disease control was significantly enhanced by the concomitant administration of MLT plus CBD with respect to CY alone (P<0.05), and the association with Ang 1-7 furtherly significantly increased CT efficacy. Both neuroimmune schedules improved the safety of CT, and in particular the association of Ang 1-7 was effective in the treatment of asthenia. This study confirms the possibility to improve the efficacy and safety of cancer CT by a neuroimmune regimen with MLT, cannabinoids, and Ang 1-7.