Adjuvant melatonin for the prevention of recurrence and mortality following lung cancer resection (AMPLCaRe): A randomized placebo controlled clinical trial

Abstract

Background: Despite curative intent resection in patients with non-small cell lung cancer (NSCLC), recurrence leading to mortality remains too common. Melatonin has shown promise for the treatment of patients with lung cancer; however, its effect following cancer resection has not been studied. We evaluated if melatonin taken after complete resection reduces lung cancer recurrence and mortality, or impacts quality of life (QOL), symptomatology or immune function. Methods: Participants received melatonin (20 mg) or placebo nightly for one year following surgical resection of primary NSCLC. The primary outcome was two-year disease-free survival (DFS). Secondary outcomes included five-year DFS, adverse events, QOL, fatigue, sleep, depression, anxiety, pain, and biomarkers assessing for immune function/inflammation. This study is registered at https://clinicaltrials.gov NCT00668707. Findings: 709 patients across eight centres were randomized to melatonin (n = 356) versus placebo (n = 353). At two years, melatonin showed a relative risk of 1¢01 (95% CI 0¢83À1¢22), p = 0¢94 for DFS. At five years, melatonin showed a hazard ratio of 0¢97 (95% CI 0¢86À1¢09), p = 0¢84 for DFS. When stratified by cancer stage (I/II and III/IV), a hazard reduction of 25% (HR 0¢75, 95% CI 0¢61À0¢92, p = 0¢005) in five-year DFS was seen for participants in the treatment arm with advanced cancer (stage III/IV). No meaningful differences were seen in any other outcomes. Interpretation: Adjuvant melatonin following resection of NSCLC does not affect DFS for patients with resected early stage NSCLC, yet may increase DFS in patients with late stage disease. Further study is needed to confirm this positive result. No beneficial effects were seen in QOL, symptoms, or immune function.

Use of Melatonin in Cancer Treatment: Where Are We?

“…The use of melatonin in non-small cell lung cancer (NSCLC) patients was also investigated, showing that melatonin improved the quality of life but did not demonstrate any protective effects against chemotherapy-related side effects [ 89 ]. Moreover, adjuvant melatonin following resection of NSCLC increased the 2-year disease-free survival (DFS) in patients with late-stage disease but did not exhibit beneficial effects in quality of life, symptoms, or immune function [ 90 ]. Further studies are needed to explore the beneficial effects of melatonin on this leading cause of death from cancer worldwide.…”

Effect of melatonin on quality of life and symptoms in patients with cancer: a systematic review and meta-analysis of randomised controlled trials

“…23 Therefore, a total of 19 articles were included in the final meta-analysis. [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] The flow chart of the literature search is shown in figure 1.…”

Adjuvant Melatonin for Uveal Melanoma (AMUM): Protocol for a Randomized Open-label Phase III Study

“…Melatonin given at a dose of 20 mg at 10 pm has shown particularly positive effects in advanced stages of cancer in earlier studies. 10 It has also been reported that systemic chemotherapy is more easily tolerated in patients who are simultaneously treated with melatonin, particularly in regards to neurotoxicity, thrombocytopenia, weight loss, and asthenia. 44 Furthermore, there are fewer cases of alopecia (hair loss) and infection in patients taking 20 mg of melatonin at 10 pm while undergoing radiotherapy.…”

“…In a recently published study on patients with nonsmall cell lung cancer, a signi cantly improved progression-free survival was seen in a subgroup of patients with advanced stage disease, however, in another, similar study no such impact was seen after a year of treatment with melatonin. 9,10 The overarching factor responsible for melatonin's impact on cancer is believed to be related to its oncostatic properties, including inhibition of tumor cell proliferation, remodeling of the cytoskeleton, antioxidative effects, and stimulation of the immune system. [11][12][13] We have recently described the rationale for adjuvant treatment with melatonin for uveal melanoma in a review of the literature.…”