A randomized placebo-controlled prevention trial of aspirin and/or resistant starch in young people with familial adenomatous polyposis

John Burn, D Timothy Bishop, Pamela D Chapman, Faye Elliott, Lucio Bertario, Malcolm G Dunlop, Diana Eccles, Anthony Ellis, D Gareth Evans, Riccardo Fodde, Eamonn R Maher, Gabriela Möslein, Hans F A Vasen, Julie Coaker, Robin K S Phillips, Steffen Bülow, John C Mathers, International CAPP consortium, Neva Haites (Collaborator)

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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.
Original languageEnglish
Pages (from-to)655-665
Number of pages11
JournalCancer Prevention Research
Volume4
Issue number5
DOIs
Publication statusPublished - May 2011

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Adenomatous Polyposis Coli
Starch
Aspirin
Placebos
Polyps
Sigmoid Colon
Rectum
Endoscopy
Colorectal Neoplasms
Randomized Controlled Trials
Adenoma
Disease Progression
Epidemiologic Studies
Mucous Membrane

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A randomized placebo-controlled prevention trial of aspirin and/or resistant starch in young people with familial adenomatous polyposis. / Burn, John; Bishop, D Timothy; Chapman, Pamela D; Elliott, Faye; Bertario, Lucio; Dunlop, Malcolm G; Eccles, Diana; Ellis, Anthony; Evans, D Gareth; Fodde, Riccardo; Maher, Eamonn R; Möslein, Gabriela; Vasen, Hans F A; Coaker, Julie; Phillips, Robin K S; Bülow, Steffen; Mathers, John C; International CAPP consortium; Haites, Neva (Collaborator).

In: Cancer Prevention Research, Vol. 4, No. 5, 05.2011, p. 655-665.

Research output: Contribution to journalArticle

Burn, J, Bishop, DT, Chapman, PD, Elliott, F, Bertario, L, Dunlop, MG, Eccles, D, Ellis, A, Evans, DG, Fodde, R, Maher, ER, Möslein, G, Vasen, HFA, Coaker, J, Phillips, RKS, Bülow, S, Mathers, JC, International CAPP consortium & Haites, N 2011, 'A randomized placebo-controlled prevention trial of aspirin and/or resistant starch in young people with familial adenomatous polyposis', Cancer Prevention Research, vol. 4, no. 5, pp. 655-665. https://doi.org/10.1158/1940-6207.CAPR-11-0106
Burn, John ; Bishop, D Timothy ; Chapman, Pamela D ; Elliott, Faye ; Bertario, Lucio ; Dunlop, Malcolm G ; Eccles, Diana ; Ellis, Anthony ; Evans, D Gareth ; Fodde, Riccardo ; Maher, Eamonn R ; Möslein, Gabriela ; Vasen, Hans F A ; Coaker, Julie ; Phillips, Robin K S ; Bülow, Steffen ; Mathers, John C ; International CAPP consortium ; Haites, Neva. / A randomized placebo-controlled prevention trial of aspirin and/or resistant starch in young people with familial adenomatous polyposis. In: Cancer Prevention Research. 2011 ; Vol. 4, No. 5. pp. 655-665.
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AU - Burn, John

AU - Bishop, D Timothy

AU - Chapman, Pamela D

AU - Elliott, Faye

AU - Bertario, Lucio

AU - Dunlop, Malcolm G

AU - Eccles, Diana

AU - Ellis, Anthony

AU - Evans, D Gareth

AU - Fodde, Riccardo

AU - Maher, Eamonn R

AU - Möslein, Gabriela

AU - Vasen, Hans F A

AU - Coaker, Julie

AU - Phillips, Robin K S

AU - Bülow, Steffen

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AU - International CAPP consortium

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N2 - 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.

AB - 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.

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