Seely Dugald, Legacy Mark, Auer Rebecca C, Fazekas Anna, Delic Edita, Anstee Caitlin, Angka Leonard, Kennedy Michael A, Tai Lee-Hwa, Zhang Tinghua, Maziak Donna E, Shamji Farid M, Sundaresan R Sudhir, Gilbert Sebastien, Villeneuve P James, Ashrafi Ahmad S, Inculet Richard, Yasufuku Kazuhiro, Waddell Thomas K, Finley Christian, Shargall Yaron, Plourde Madelaine, Fergusson Dean A, Ramsay Tim, Seely Andrew J E
Ottawa Integrative Cancer Centre, Otttawa, Canada.
Ottawa Hospital Research Institute, Ottawa, Canada.
EClinicalMedicine. 2021 Feb 27;33:100763. doi: 10.1016/j.eclinm.2021.100763. eCollection 2021 Mar.
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.
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.
709 patients across eight centres were randomized to melatonin ( = 356) versus placebo ( = 353). At two years, melatonin showed a relative risk of 1·01 (95% CI 0·83-1·22), = 0·94 for DFS. At five years, melatonin showed a hazard ratio of 0·97 (95% CI 0·86-1·09), = 0·84 for DFS. When stratified by cancer stage (I/II and III/IV), a hazard reduction of 25% (HR 0·75, 95% CI 0·61-0·92, = 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.
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.
This study was funded by the Lotte and John Hecht Memorial Foundation and the Gateway for Cancer Research Foundation.
尽管对非小细胞肺癌（NSCLC）患者进行了根治性切除，但导致死亡的复发情况仍然很常见。褪黑素已显示出对肺癌患者治疗的前景；然而，其在癌症切除后的效果尚未得到研究。我们评估了在完全切除后服用褪黑素是否能降低肺癌复发率和死亡率，或影响生活质量（QOL）、症状或免疫功能。
在原发性NSCLC手术切除后，参与者每晚接受褪黑素（20毫克）或安慰剂治疗，为期一年。主要结局是两年无病生存期（DFS）。次要结局包括五年DFS、不良事件、QOL、疲劳、睡眠、抑郁、焦虑、疼痛以及评估免疫功能/炎症的生物标志物。本研究已在https://clinicaltrials.gov注册，注册号为NCT00668707。
八个中心的709名患者被随机分为褪黑素组（n = 356）和安慰剂组（n = 353）。两年时，褪黑素组的DFS相对风险为1.01（95% CI 0.83 - 1.22），P = 0.94。五年时，褪黑素组的DFS风险比为0.97（95% CI 0.86 - 1.09），P = 0.84。按癌症分期（I/II期和III/IV期）分层时，晚期癌症（III/IV期）治疗组参与者的五年DFS风险降低了25%（HR 0.75，95% CI 0.61 - 0.92，P = 0.005）。在任何其他结局方面均未观察到有意义的差异。
NSCLC切除术后辅助使用褪黑素对早期NSCLC切除患者的DFS无影响，但可能增加晚期疾病患者的DFS。需要进一步研究来证实这一阳性结果。在QOL、症状或免疫功能方面未观察到有益效果。
本研究由乐天和约翰·赫克特纪念基金会以及癌症研究基金会资助。
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