title: A randomized placebo-controlled prevention trial of aspirin and/or resistant starch in young people with familial adenomatous polyposis.
abstract: Evidence supporting aspirin and resistant starch (RS) for colorectal cancer prevention comes from epidemiologic and laboratory studies (aspirin and RS) and randomized controlled clinical trials (aspirin). Familial adenomatous polyposis (FAP) strikes young people and, untreated, confers virtually a 100% risk of colorectal cancer and early death. We conducted an international, multicenter, randomized, placebo-controlled trial of aspirin (600 mg/d) and/or RS (30 g/d) for from 1 to 12 years to prevent disease progression in FAP patients from 10 to 21 years of age. In a 2 × 2 factorial design, patients were randomly assigned to the following four study arms: aspirin plus RS placebo; RS plus aspirin placebo; aspirin plus RS; RS placebo plus aspirin placebo; they were followed with standard annual clinical examinations including endoscopy. The primary endpoint was polyp number in the rectum and sigmoid colon (at the end of intervention), and the major secondary endpoint was size of the largest polyp. A total of 206 randomized FAP patients commenced intervention, of whom 133 had at least one follow-up endoscopy and were therefore included in the primary analysis. Neither intervention significantly reduced polyp count in the rectum and sigmoid colon: aspirin relative risk = 0.77 (95% CI, 0.54-1.10; versus nonaspirin arms); RS relative risk = 1.05 (95% CI, 0.73-1.49; versus non-RS arms). There was a trend toward a smaller size of largest polyp in patients treated with aspirin versus nonaspirin--mean 3.8 mm versus 5.5 mm for patients treated 1 or more years (adjusted P = 0.09) and mean 3.0 mm versus 6.0 mm for patients treated more than 1 year (P = 0.02); there were similar weaker trends with RS versus non-RS. Exploratory translational endpoints included crypt length (which was significantly shorter in normal-appearing mucosa in the RS group over time) and laboratory measures of proliferation (including Ki67). This clinical trial is the largest ever conducted in the setting of FAP and found a trend of reduced polyp load (number and size) with 600 mg of aspirin daily. RS had no clinical effect on adenomas.
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK. john.burn@ncl.ac.uk
authors.forename: John
authors.initials: J
authors.lastname: Burn
authors.forename: D Timothy
authors.initials: DT
authors.lastname: Bishop
authors.forename: Pamela D
authors.initials: PD
authors.lastname: Chapman
authors.forename: Faye
authors.initials: F
authors.lastname: Elliott
authors.forename: Lucio
authors.initials: L
authors.lastname: Bertario
authors.forename: Malcolm G
authors.initials: MG
authors.lastname: Dunlop
authors.forename: Diana
authors.initials: D
authors.lastname: Eccles
authors.forename: Anthony
authors.initials: A
authors.lastname: Ellis
authors.forename: D Gareth
authors.initials: DG
authors.lastname: Evans
authors.forename: Riccardo
authors.initials: R
authors.lastname: Fodde
authors.forename: Eamonn R
authors.initials: ER
authors.lastname: Maher
authors.forename: Gabriela
authors.initials: G
authors.lastname: Möslein
authors.forename: Hans F A
authors.initials: HF
authors.lastname: Vasen
authors.forename: Julie
authors.initials: J
authors.lastname: Coaker
authors.forename: Robin K S
authors.initials: RK
authors.lastname: Phillips
authors.forename: Steffen
authors.initials: S
authors.lastname: Bülow
authors.forename: John C
authors.initials: JC
authors.lastname: Mathers
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000517:prevention & control*; D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D002648:Child; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007390:International Agencies; D008297:Male; D011379:Prognosis; D012007:Rectum / Q000187:drug effects; D013213:Starch / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D013213:Starch; D001241:Aspirin