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

Abstract

BackgroundMelatonin (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.MethodsAfter 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.ResultsThe 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; I2=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; I2=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; I2=0%) and various solid tumor patients (RR =2.31; 95% CI, 1.78–2.99; P<0.00001; I2=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.ConclusionMLT 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.

Melatonin Administered before or after a Cytotoxic Drug Increases Mammary Cancer Stabilization Rates in HER2/Neu Mice

“…Whatever the mechanism beneath our findings, they add to the growing list of beneficial effects of MT as an adjuvant to anticancer therapy [8,9,11,12,14,43,44]. In particular, our data suggest that MT can enhance the effectiveness of chemotherapy drugs most notably in cases ZT, Zeitgeber Time; n/d, not determined.…”

“…MT was shown to produce oncostatic effect in several cancers [9] and can influence body responses to cytostatic drugs [10]. The available data on the need for combinations of the chemotherapy regimen, chronobiotic agents, and the appropriate time of their administration do not allow to draw unambiguous conclusions about the therapeutic value of such approaches, which are obviously promising [11][12][13][14][15]. In the present study, we used HER2/neu female mice with spontaneous mammary adenocarcinomas to investigate if cytostatic therapy may be influenced by MT provided for a week before or 3 weeks after administering the cytostatic chemotherapy at extreme times of the working day generally adopted at healthcare facilities.…”

The emergence of melatonin in oncology: Focus on colorectal cancer

“…Thus, epidemiological reports published since this date were not conclusive, perhaps by the inaccurate definition of “circadian dysregulation,” obviating the chronic and yet ignored alterations of the circadian cycle by modern lifestyles, or from the bias in the estimates of chronodisruption according to interindividual variations in exposition and/or homeostatic adaptation ability . However, despite discrepancies, the accumulated evidence from the systematic and critical reconsideration of epidemiological literature and its meta‐analysis has recently confirmed the positive outcome of cancer patients receiving melatonin . Moreover, a population‐based case‐control study has pointed out CRC as one of the neoplasms in which the association between prolonged night‐shift work among men and tumor incidence is statistically stronger …”

“…70 However, despite discrepancies, the accumulated evidence from the systematic and critical reconsideration of epidemiological literature and its meta-analysis has recently confirmed the positive outcome of cancer patients receiving melatonin. 71 Moreover, a population-based case-control study has pointed out CRC as one of the neoplasms in which the association between prolonged night-shift work among men and tumor incidence is statistically stronger. 72 Once released into the blood and cerebrospinal fluid from photoreceptor-derived pinealocytes, it is widely known the multitasking functionality of picomolar/nanomolar intracellular melatonin in the fine tuning of the "time of the day" (circadian clock) and the "time of the year" (the calendar of seasonal changes).…”

Integration of Chronobiological Concepts for NSCLC Management

“…Two meta-analyses appeared to confirm survival benefits associated with melatonin therapy in cancer patients [98,99]. One analysis has focused upon 8 trials that used a dosage of 20 mg of melatonin, while the second one reviewed 21 clinical trials on solid tumors using various doses of melatonin [98,99].…”