A Randomized Placebo-controlled Prevention Trial of Aspirin and/or Resistant Starch in Young People with Familial Adenomatous Polyposis

摘要

Evidence supporting aspirin and resistant starch (RS) for colorectal cancer prevention comes from epidemiological 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/day) and/or RS (30 g/day) 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 1 follow-up endoscopy and so were included in the primary analysis. Neither intervention significantly reduced polyp count in the rectum and sigmoid colon: aspirin relative risk (RR) = 0.77 (95% confidence interval [CI], 0.54–1.10; versus non-aspirin arms); RS RR = 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 non-aspirin—mean 3.8 mm versus 5.5 mm for patients treated one or more years (adjusted P = 0.09) and mean 3.0 mm versus 6.0 mm for patients treated more than one year (P = 0.02); there were weaker such 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 one 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.