Current Evidence to Justify, and the Methodological Considerations for a Randomised Controlled Trial Testing the Hypothesis that Statins Prevent the Malignant Progression of Barrett's Oesophagus

Journal of International Translational Medicine

Leo Alexandre¹  David Thurtle²  Yoon K Loke³  Ed Cheong⁴  Andrew Hart⁵ 

[1] Academic Clinical Fellow, Department of Gastroenterology, Norwich Medical School-University of East Anglia, Norwich, UK;Academic Foundation Trainee, Department of General Surgery, Norfolk and Norwich University Hospital, Colney Lane, Norwich, UK;Clinical Senior Lecturer, Norwich Medical School- University of East Anglia, Norwich, UK;Consultant Upper GI Surgeon, Department of General Surgery, Norfolk and Norwich University Hospital, Norwich, UK;Senior Lecturer in Gastroenterology, Norwich Medical School and Honorary Consultant Gastroenterologist, Department of Gastroenterology, Norfolk and Norwich University Hospital, Norwich, UK;

关键词: Hydroxymethylglutaryl-CoA Reductase Inhibitors;    Esophageal Neoplasms;    Barrett Esophagus;    Deglutition Disorders;   

DOI  :  10.11910/2227-6394.2014.02.04.14

来源: DOAJ

【 摘 要 】

Barrett’s oesophagus is the predominant risk factor for oesophageal adenocarcinoma, a cancer whose incidence is increasing and which has a poor prognosis. This article reviews the latest experimental and epidemiological evidence justifying the development of a randomised controlled trial investigating the hypothesis that statins prevent the malignant progression of Barrett’s oesophagus, and explores the methodological considerations for such a trial. The experimental evidence suggests anti-carcinogenic properties of statins on oesophageal cancer cell lines, based on the inhibition of the mevalonate pathway and the production of pro-apoptotic proteins. The epidemiological evidence reports inverse associations between statin use and the incidence of oesophageal carcinoma in both general population and Barrett’s oesophagus cohorts. Such a randomised controlled trial would be a large multi-centre trial, probably investigating simvastatin, given the wide clinical experience with this drug, relatively low side-effect profile and low financial cost. As with any clinical trial, high adherence is important, which could be increased with therapy, patient, doctor and system-focussed interventions. We would suggest there is now sufficient evidence to justify a full clinical trial that attempts to prevent this aggressive cancer in a high-risk population.

【 授权许可】

Unknown