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


Journal

EClinicalMedicine
ISSN: 2589-5370
Titre abrégé: EClinicalMedicine
Pays: England
ID NLM: 101733727

Informations de publication

Date de publication:
Mar 2021
Historique:
received: 18 08 2020
revised: 20 01 2021
accepted: 02 02 2021
entrez: 8 3 2021
pubmed: 9 3 2021
medline: 9 3 2021
Statut: epublish

Résumé

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 ( 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.

Sections du résumé

BACKGROUND 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 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 RESULTS
709 patients across eight centres were randomized to melatonin (
INTERPRETATION CONCLUSIONS
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.
FUNDING BACKGROUND
This study was funded by the Lotte and John Hecht Memorial Foundation and the Gateway for Cancer Research Foundation.

Identifiants

pubmed: 33681747
doi: 10.1016/j.eclinm.2021.100763
pii: S2589-5370(21)00043-2
pmc: PMC7930365
doi:

Banques de données

ClinicalTrials.gov
['NCT00668707']

Types de publication

Journal Article

Langues

eng

Pagination

100763

Informations de copyright

© 2021 The Authors.

Déclaration de conflit d'intérêts

Dr. Villeneuve reports ‘other’ from Minogue Medical, outside the submitted work. All other authors have no conflicts of interest to disclose.

Références

J Natl Cancer Inst. 2002 Aug 21;94(16):1247-9
pubmed: 12189228
Curr Top Med Chem. 2002 Feb;2(2):113-32
pubmed: 11899096
Cytokine. 1999 Jan;11(1):80-6
pubmed: 10080883
Integr Cancer Ther. 2012 Dec;11(4):293-303
pubmed: 22019490
Surg Technol Int. 2017 Jul 25;30:231-235
pubmed: 28395387
J Pineal Res. 2003 Aug;35(1):12-5
pubmed: 12823608
J Clin Oncol. 2006 Jan 20;24(3):419-30
pubmed: 16421421
Nutr J. 2010 Dec 22;9:69
pubmed: 21176210
Cancer Cell. 2017 Aug 14;32(2):135-154
pubmed: 28810142
J Thorac Oncol. 2010 Jul;5(7):988-92
pubmed: 20453690
Integr Cancer Ther. 2018 Sep;17(3):793-805
pubmed: 29558830
Semin Oncol. 2006 Feb;33(1 Suppl 1):S25-31
pubmed: 16472706
Curr Med Chem. 2010;17(36):4462-81
pubmed: 21062257
PLoS One. 2013 May 17;8(5):e63773
pubmed: 23691095
Semin Cancer Biol. 2018 Oct;52(Pt 1):103-109
pubmed: 29183778
J Paediatr Child Health. 2005 Jan-Feb;41(1-2):21-2
pubmed: 15670218
J Pineal Res. 2005 Nov;39(4):360-6
pubmed: 16207291
Curr Opin Clin Nutr Metab Care. 2009 May;12(3):223-6
pubmed: 19318937
Eur J Cardiothorac Surg. 2019 Jan 1;55(1):91-115
pubmed: 30304509
Am J Hematol. 1995 Jun;49(2):143-8
pubmed: 7771466
Int J Exp Pathol. 2006 Apr;87(2):81-7
pubmed: 16623752
J Psychosom Res. 1995 Apr;39(3):315-25
pubmed: 7636775
Cancer Invest. 2009 Dec;27(10):989-97
pubmed: 19909014
Anticancer Res. 2014 Dec;34(12):7327-37
pubmed: 25503168
Eur J Cancer. 2004 Sep;40(14):2041-6
pubmed: 15341976
Lancet Oncol. 2006 Oct;7(10):829-36
pubmed: 17012045
J Natl Compr Canc Netw. 2017 Apr;15(4):504-535
pubmed: 28404761
CA Cancer J Clin. 2018 Nov;68(6):394-424
pubmed: 30207593
J Clin Oncol. 2013 Apr 1;31(10):1271-6
pubmed: 23439759
Lung Cancer. 2006 Jul;53(1):97-101
pubmed: 16698114

Auteurs

Dugald Seely (D)

Ottawa Integrative Cancer Centre, Otttawa, Canada.
Ottawa Hospital Research Institute, Ottawa, Canada.
Canadian College of Naturopathic Medicine, Toronto, Canada.

Mark Legacy (M)

Ottawa Integrative Cancer Centre, Otttawa, Canada.
Ottawa Hospital Research Institute, Ottawa, Canada.

Rebecca C Auer (RC)

Ottawa Hospital Research Institute, Ottawa, Canada.

Anna Fazekas (A)

Ottawa Hospital Research Institute, Ottawa, Canada.

Edita Delic (E)

Ottawa Hospital Research Institute, Ottawa, Canada.

Caitlin Anstee (C)

Ottawa Hospital Research Institute, Ottawa, Canada.

Leonard Angka (L)

Ottawa Hospital Research Institute, Ottawa, Canada.

Michael A Kennedy (MA)

Ottawa Hospital Research Institute, Ottawa, Canada.

Lee-Hwa Tai (LH)

Ottawa Hospital Research Institute, Ottawa, Canada.

Tinghua Zhang (T)

Ottawa Hospital Research Institute, Ottawa, Canada.

Donna E Maziak (DE)

Ottawa Hospital Research Institute, Ottawa, Canada.
University of Ottawa Department of Surgery, Ottawa, Canada.

Farid M Shamji (FM)

Ottawa Hospital Research Institute, Ottawa, Canada.
University of Ottawa Department of Surgery, Ottawa, Canada.

R Sudhir Sundaresan (RS)

Ottawa Hospital Research Institute, Ottawa, Canada.
University of Ottawa Department of Surgery, Ottawa, Canada.

Sebastien Gilbert (S)

Ottawa Hospital Research Institute, Ottawa, Canada.
University of Ottawa Department of Surgery, Ottawa, Canada.

P James Villeneuve (PJ)

Ottawa Hospital Research Institute, Ottawa, Canada.
University of Ottawa Department of Surgery, Ottawa, Canada.

Ahmad S Ashrafi (AS)

Surrey Memorial Hospital/Fraser Health Authority, Surrey, Canada.

Richard Inculet (R)

London Health Sciences Centre, London, Canada.

Kazuhiro Yasufuku (K)

University Health Network, Toronto, Canada.

Thomas K Waddell (TK)

University Health Network, Toronto, Canada.

Christian Finley (C)

St. Joseph's Healthcare & McMaster University, Hamilton, Canada.

Yaron Shargall (Y)

St. Joseph's Healthcare & McMaster University, Hamilton, Canada.

Madelaine Plourde (M)

QEII Health Sciences Centre/Capital Health, Halifax, Canada.

Dean A Fergusson (DA)

Ottawa Hospital Research Institute, Ottawa, Canada.
University Health Network, Toronto, Canada.

Tim Ramsay (T)

Ottawa Hospital Research Institute, Ottawa, Canada.

Andrew J E Seely (AJE)

Ottawa Hospital Research Institute, Ottawa, Canada.
University of Ottawa Department of Surgery, Ottawa, Canada.

Classifications MeSH