Therapeutic Potential of Melatonin Counteracting Chemotherapy-Induced Toxicity in Breast Cancer Patients: A Systematic Review

Abstract

The purpose of this systematic review is to provide an overview of the existing knowledge on the therapeutic potential of melatonin to counteract the undesirable effects of chemotherapy in breast cancer patients. To this aim, we summarized and critically reviewed preclinical- and clinical-related evidence according to the PRISMA guidelines. Additionally, we developed an extrapolation of melatonin doses in animal studies to the human equivalent doses (HEDs) for randomized clinical trials (RCTs) with breast cancer patients. For the revision, 341 primary records were screened, which were reduced to 8 selected RCTs that met the inclusion criteria. We assembled the evidence drawn from these studies by analyzing the remaining gaps and treatment efficacy and suggested future translational research and clinical trials. Overall, the selected RCTs allow us to conclude that melatonin combined with standard chemotherapy lines would derive, at least, a better quality of life for breast cancer patients. Moreover, regular doses of 20 mg/day seemed to increase partial response and 1-year survival rates. Accordingly, this systematic review leads us to draw attention to the need for more RCTs to provide a comprehensive view of the promising actions of melatonin in breast cancer and, given the safety profile of this molecule, adequate translational doses should be established in further RCTs.

Unveiling the Protective Role of Melatonin in Osteosarcoma: Current Knowledge and Limitations

“…An additional component to reflect on is the limiting nature of integrating preclinical data in a clinical setting. Reports suggest that factors such as (1) differences in the circadian rhythms (known to influence cancer incidence and progression), (2) differences in metabolic rates (that should affect the response to anti-cancer drug interventions), (3) immune responses, and (4) genetic variations since humans are diurnal when compared to most experimental animals (rats or mice), known to be nocturnal, must be carefully considered in melatonin-related research [165][166][167][168][169].…”

“…While being diurnal or nocturnal may not affect melatonin synthesis, the fact that this may affect susceptibility to the disease, expression of genes and proteins, immune responses, and drug metabolism must be factored in to determine optimal dosage and the timing and frequency of melatonin intervention while translating melatonin-related anti-cancer effects from bench to bedside [165][166][167][168][169].…”