Eicosapentaenoic acid reduces rectal polyp number and size in familial adenomatous polyposis

• Published in: Gut Vol. 59; no. 7; pp. 918 - 925
• Main Authors: West, Nicholas J, Clark, Susan K, Phillips, Robin K S, Hutchinson, John M, Leicester, Roger J, Belluzzi, Andrea, Hull, Mark A
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Society of Gastroenterology 01.07.2010; BMJ Publishing Group; BMJ Publishing Group LTD
• Subjects: Adenomatous Polyposis Coli - metabolism; Adenomatous Polyposis Coli - prevention & control; Adenomatous Polyposis Coli - surgery; Adolescent; Adult; Aged; Anticarcinogenic Agents - adverse effects; Anticarcinogenic Agents - therapeutic use; Biological and medical sciences; Chemoprevention; Colectomy; Colorectal cancer; Disease Progression; Double-Blind Method; eicosapentaenoic acid; Eicosapentaenoic Acid - adverse effects; Eicosapentaenoic Acid - therapeutic use; familial adenomatous polyposis; Fatty acids; Fatty Acids - metabolism; Female; Fish oils; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Intestinal Mucosa - metabolism; Intestinal Polyps - metabolism; Intestinal Polyps - pathology; Intestinal Polyps - prevention & control; Male; Medical sciences; Middle Aged; omega-3 polyunsaturated fatty acid; Patient Compliance; Rectal Neoplasms - metabolism; Rectal Neoplasms - pathology; Rectal Neoplasms - prevention & control; Rodents; Sigmoidoscopy; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Treatment Outcome; Tumors; Young Adult; Size; Gastroenterology; Rectum; Digestive diseases; Intestinal disease; Familial adenomatous polyposis coli; n-3 fatty acid; Eicosapentaenoic acid; Genetic disease; Polyp
• ISSN: 0017-5749; 1468-3288
• DOI: 10.1136/gut.2009.200642

ObjectiveThe omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) has anticolorectal cancer activity in vitro and in preclinical models. The present study tested whether a novel, enteric-coated formulation of EPA, as the free fatty acid (EPA-FFA), has chemopreventative efficacy in patients with familial adenomatous polyposis (FAP), in a randomised, double-blind, placebo-controlled trial.MethodsPatients undergoing endoscopic surveillance of their retained rectum postcolectomy were randomised to EPA-FFA (SLA Pharma) 2 g daily or placebo for 6 months. The number and size of polyps in an area of mucosa defined by a tattoo were determined before and after intervention. Global rectal polyp burden was scored (−1, 0, +1) by examination of video endoscopy records. Mucosal fatty acid content was measured by gas chromatography–mass spectrometry.Results55 patients with FAP were evaluated by an intention-to-treat analysis (EPA-FFA 28, placebo 27). Treatment with EPA-FFA for 6 months was associated with a mean 22.4% (95% CI 5.1% to 39.6%) reduction in polyp number (p=0.012) and a 29.8% (3.6% to 56.1%) decrease in the sum of polyp diameters (p=0.027). Global polyp burden worsened over 6 months in the placebo group (−0.34) unlike the EPA-FFA group (+0.09, difference 0.42 (0.10–0.75), p=0.011). EPA-FFA treatment led to a mean 2.6-fold increase in mucosal EPA levels (p=0.018 compared with placebo). EPA-FFA was well tolerated with an incidence of adverse events similar to placebo.ConclusionsEPA-FFA has chemopreventative efficacy in FAP, to a degree similar to that previously observed with selective cyclo-oxygenase-2 inhibitors. EPA holds promise as a colorectal cancer chemoprevention agent with a favourable safety profile.Clinical trial numberNCT00510692.