Clinical Study of Melatonin in Untreatable Advanced Cancer Patients

Abstract

It is known that the pineal gland has some antitumor activity. Melatonin, its most important hormone, has been shown to inhibit tumor growth in vivo and in vitro. Moreover, some investigations have demonstrated an altered melatonin secretion in cancer patients. Despite these interesting data, clinical trials have never been carried out to evaluate the effects of melatonin on human neoplasms. The aim of this study was to draw some preliminary conclusions on melatonin therapy in advanced human neoplasms. Nineteen patients suffering from advanced solid tumors, which did not respond to standard therapies, entered the study. Performance status (PS) was 20 or less in 9 cases, and more than 20 in the other 10. Melatonin was given intramuscularly at a daily dose of 20 mg at 3.00 p.m., followed by a maintenance period with lower doses in patients who had a remission, a stabilization of disease or an improvement in PS. Among patients with a PS higher than 20, a partial response was achieved in one case with cancer of the pancreas; moreover, 5 of 10 had stable disease, but the other 4 cases had a progression; an evident improvement of PS was obtained in 6 of the 10 cases. In contrast, among patients with a very poor PS, 7 of 9 died within the first 2 months of therapy. This preliminary study would suggest that melatonin may be of some value in treating cancer patients in whom standard antitumor therapies have failed, particularly in improving their PS and quality of life.

Melatonin-Induced Oncostasis, Mechanisms and Clinical Relevance

“…Chemotherapy was well tolerated in patients receiving melatonin, and the frequency of myelosuppression, neuropathy, and cachexia was significantly lower in the melatonin group The clinical response consisted of minor response in 2, stable disease in 6 and progressive disease in the remaining 12 patients. Non-progressing patients showed a significant decline in VEGF mean concentrations, whereas no effect was achieved in progressing patients [266] J Compared to subjects on placebo, subjects randomized to melatonin experienced significantly greater improvements in subjective sleep quality as measured by the PSQI, including domains on sleep quality, daytime dysfunction and total score. There were no significant differences in measures of depression or hot flashes controlled study in patients with advanced lung or gastro-intestinal cancer and cachexia, melatonin (20 mg/day) was ineffective to modify appetite, weight, toxicity, or survival from baseline to day 28 [208].…”

The melatonin immunomodulatory actions in radiotherapy

“…Also, in in vitro studies, using melatonin reduces breast cancer cell viability (Jardim-Perassi et al 2014;Jardim et al 2013). In a clinical study including 20 metastatic patients, the administration of melatonin resulted in a significant reduction in VEGF blood levels, whereas no effect was seen in progressing patients (Lissoni et al 2001). …”

Therapeutic Effect of Melatonin in Experimental Uveitis

“…28,29 Several lines of evidence suggest that melatonin may act as a protective agent in ocular conditions such as photokeratitis, cataract, glaucoma, retinopathy of prematurity, and ischemia/reperfusion injury (for a review see 30 ). Besides its antioxidant effect, several other mechanisms are considered to be involved in neuroprotection induced by melatonin, including its interaction with calmodulin 31 and microtubular components, 32 blockade of intracellular Ca 2ϩ levels increase, 33 inhibition of the nitridergic pathway, 34,35 decrease in vascular endothelial growth factor levels, 36,37 and decrease in retinal glutamate synaptic concentrations, 38 among others. In this context, the aim of the present work was to analyze the therapeutic effect of melatonin in the golden hamster EIU.…”