Melatonin as Cancer Treatment Although it is not usually considered a standard antioxidant, melatonin, the hormone secreted by the pineal gland in response to cycles of light and dark, has exhibited potent free radical-scavenging properties against hydroxyl and peroxyl radicals.108 Melatonin has also been found to have some interesting anti-tumor properties in vitro. It increases p53 expression in breast cancer cells, and therefore significantly reduces cell proliferation.8 Impaired p53 expression is associated with many human cancers.109 Melatonin is also known to modify many cytokines, including TNF, IL1, IL-2, IL-6, and gamma-interferon, in ways consistent with increased host defense against cancers.110 Melatonin, perhaps through reduction of TNF secretion, has been shown to reduce cachexia in patients with metastatic solid tumors. Patients taking melatonin (20 mg/day) were found to have significantly less weight loss (3 kg vs. 16 kg) and disease progression (53% vs. 90%) than those treated with supportive care alone.111 In another study, 63 patients with non-small cell lung cancer refractory to cisplatin therapy were randomized to receive either 10 mg/day of melatonin or supportive care alone. Patients receiving melatonin lived longer on average than those receiving supportive care alone (6 vs. 3 months) and were more likely to survive for one year (8/31 survivors vs. 2/32). No drug-related toxicity was noted by the authors.112 Treatment with melatonin (20 mg/day) was also associated with greater one-year survival than supportive care alone in patients with brain metastases.113 Other studies have noted increased survival in malignant melanoma114 and patients with metastatic disease.115 The latter study stressed that based in its effects on the immune system, melatonin could be tested in association with other anti-tumor treatments.115 The DiBella multitherapy of cancer, of which melatonin is a part (along with many other agents), was found not to have sufficient efficacy against advanced cancer to warrant further investigation.116 Animal experiments suggest doses as high as 250 mg/kg are non-toxic.117 Melatonin with Radiation In a randomized trial including 30 patients with glioblastoma, the effect of radiotherapy plus 20 mg/day of melatonin was compared to that of radiotherapy alone. At the end of one year, six of the 14 patients receiving melatonin were still living, compared to one of the 16 undergoing radiotherapy alone. The authors also noted fewer side effects from radiotherapy in patients taking melatonin.118 Melatonin with Chemotherapy Melatonin has been studied a number of times as an adjunct to standard chemotherapy in humans. A phase II study used tamoxifen plus melatonin (20 mg/day) in the treatment of metastatic breast cancer which had progressed under treatment with tamoxifen alone. Four of the 14 patients tested had partial response to this combination, with a median of eight months before disease progression. Treatment was well-tolerated and relief of anxiety or depression was noted by many patients.19 A similar study was conducted using the same combination of treatments in patients with metastatic solid tumors other than breast cancer which had not responded to previous chemotherapies. Partial response or stable disease was seen in 16/25 patients. One year survival was seen in 7/25 patients.119 In another phase II study, melatonin (20 mg/day) led to a normalization of platelet counts in nine of twelve breast cancer patients who acquired thrombocytopenia during epirubicin therapy. Objective tumor regression was noted in five of the 12 patients.120 A randomized trial investigated the difference between melatonin (20 mg/day), cisplatin, and etoposide, and treatment with cisplatin and etoposide alone in advanced non-small cell lung cancer. One-year survival was significantly higher in patients receiving adjunctive melatonin compared to standard chemotherapy alone (15 of 34 vs. 7 of 36). There was a non-significant trend toward greater tumor response in melatonin-treated patients as well (11 of 34 vs. 6 of 36). Myelosuppression, neuropathy, and cachexia were noted less frequently in patients receiving melatonin than in those that were receiving only chemotherapy.121 A double-blind trial was unable to replicate this protective effect of melatonin on the myelosuppression mediated by carboplatin and etoposide. This may reflect the effect higher doses of chemotherapeutic agents given in the second trial. The authors concluded that potentiation of the effect of chemotherapy by melatonin was unlikely.122 Concomitant therapy with melatonin (40 mg/day) has been found to increase the effect of interleukin-2 against a variety of solid cancers.123 The combination of melatonin (40 mg/day) and interleukin-2 has been found to be a more effective treatment than cisplatin and etoposide in non-small cell lung cancer.124 Alternative Medicine Reviews, 1999;4(5):304-329 Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. 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