Therapeutic strategies of melatonin in cancer patients: a systematic review and meta-analysis

Background: Melatonin (MLT), a kind of neuroendocrine active substance, has been reported to function in the treatment of tumors. However, there remain controversies about the curative effect of MLT in tumors in clinical studies. This study investigates the efficacy of MLT on tumor therapeutic strategies by meta-analysis. Methods: After searching several main literature databases, a total of 5,057 articles were obtained and screened by inclusion and exclusion criteria. The tumor remission rate, overall survival rate, and incidence of side effects were recorded and analyzed in the included study patients. Group analysis and sensitivity analysis were performed to examine the sources of heterogeneity in the pooled studies. Results: The tumor remission rate in the MLT group was significantly higher than that in the control group (relative risk [RR] = 2.25; 95% CI, 1.86-2.71; P < 0.00001; I-2 = 9%). Likewise, the MLT group had an overall survival rate of 28.24% (n = 294/1,041), which was greatly increased compared with the control group (RR = 2.07; 95% CI, 1.55-2.76; P < 0.00001; I-2 = 55%). And, MLT could significantly enhance the overall survival rate in non-small-cell lung cancer patients (RR = 2.13; 95% CI, 1.41-3.24; P = 0.0004; I-2 = 0%) and various solid tumor patients (RR = 2.31; 95% CI, 1.78-2.99; P < 0.00001; I-2 = 0%). It was further proved that MLT could effectively reduce the incidence of neurotoxicity (RR = 0.30, 95% CI, 0.19-0.45; P < 0.00001), thrombocytopenia (RR = 0.23; 95% CI, 0.16-0.33; P < 0.00001), and asthenia (RR = 0.43, 95% CI, 0.38-0.49; P < 0.00001) during chemotherapy. Conclusion: MLT exerts positive influence in tumor therapeutic strategies, including improving tumor remission rate and overall survival rate, while reducing the incidence of chemotherapy side effects. Further large-scale randomized clinical trials (RCTs) are urgently required to verify therapeutic effects of MLT in tumors by various clinical research centers.