Primary chemoprevention of familial adenomatous polyposis with sulindac

Francis M Giardiello, Vincent W. Yang, Linda M. Hylind, Anne J. Krush, Gloria M. Petersen, Jill Brensinger Trimbath, Steven Piantadosi, Elizabeth Garrett, Deborah E. Geiman, Walter Hubbard, G. J A Offerhaus, Stanley R. Hamilton

Research output: Contribution to journalArticle

Abstract

Background: Familial adenomatous polyposis is caused by a germ-line mutation in the adenomatous polyposis coli gene and is characterized by the development of hundreds of colorectal adenomas and, eventually, colorectal cancer. Nonsteroidal antiinflammatory drugs can cause regression of adenomas, but whether they can prevent adenomas is unknown. Methods: We conducted a randomized, doubleblind, placebo-controlled study of 41 young subjects (age range, 8 to 25 years) who were genotypically affected with familial adenomatous polyposis but phenotypically unaffected. The subjects received either 75 or 150 mg of sulindac orally twice a day or identical-appearing placebo tablets for 48 months. The number and size of new adenomas and side effects of therapy were evaluated every four months for four years, and the levels of five major prostaglandins were serially measured in biopsy specimens of normal-appearing colorectal mucosa. Results: After four years of treatment, the average rate of compliance exceeded 76 percent in the sulindac group, and mucosal prostaglandin levels were lower in this group than in the placebo group. During the course of the study, adenomas developed in 9 of 21 subjects (43 percent) in the sulindac group and 11 of 20 subjects in the placebo group (55 percent) (P=0.54). There were no significant differences in the mean number (P=0.69) or size (P=0.17) of polyps between the groups. Sulindac did not slow the development of adenomas, according to an evaluation involving linear longitudinal methods. Conclusions: Standard doses of sulindac did not prevent the development of adenomas in subjects with familial adenomatous polyposis.

Original languageEnglish (US)
Pages (from-to)1054-1059
Number of pages6
JournalNew England Journal of Medicine
Volume346
Issue number14
DOIs
StatePublished - Apr 4 2002

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Sulindac
Adenomatous Polyposis Coli
Chemoprevention
Adenoma
Placebos
Prostaglandins
APC Genes
Germ-Line Mutation
Polyps
Tablets
Colorectal Neoplasms
Mucous Membrane
Anti-Inflammatory Agents
Biopsy
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

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Primary chemoprevention of familial adenomatous polyposis with sulindac. / Giardiello, Francis M; Yang, Vincent W.; Hylind, Linda M.; Krush, Anne J.; Petersen, Gloria M.; Brensinger Trimbath, Jill; Piantadosi, Steven; Garrett, Elizabeth; Geiman, Deborah E.; Hubbard, Walter; Offerhaus, G. J A; Hamilton, Stanley R.

In: New England Journal of Medicine, Vol. 346, No. 14, 04.04.2002, p. 1054-1059.

Research output: Contribution to journalArticle

Giardiello, FM, Yang, VW, Hylind, LM, Krush, AJ, Petersen, GM, Brensinger Trimbath, J, Piantadosi, S, Garrett, E, Geiman, DE, Hubbard, W, Offerhaus, GJA & Hamilton, SR 2002, 'Primary chemoprevention of familial adenomatous polyposis with sulindac', New England Journal of Medicine, vol. 346, no. 14, pp. 1054-1059. https://doi.org/10.1056/NEJMoa012015
Giardiello, Francis M ; Yang, Vincent W. ; Hylind, Linda M. ; Krush, Anne J. ; Petersen, Gloria M. ; Brensinger Trimbath, Jill ; Piantadosi, Steven ; Garrett, Elizabeth ; Geiman, Deborah E. ; Hubbard, Walter ; Offerhaus, G. J A ; Hamilton, Stanley R. / Primary chemoprevention of familial adenomatous polyposis with sulindac. In: New England Journal of Medicine. 2002 ; Vol. 346, No. 14. pp. 1054-1059.
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AU - Yang, Vincent W.

AU - Hylind, Linda M.

AU - Krush, Anne J.

AU - Petersen, Gloria M.

AU - Brensinger Trimbath, Jill

AU - Piantadosi, Steven

AU - Garrett, Elizabeth

AU - Geiman, Deborah E.

AU - Hubbard, Walter

AU - Offerhaus, G. J A

AU - Hamilton, Stanley R.

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N2 - Background: Familial adenomatous polyposis is caused by a germ-line mutation in the adenomatous polyposis coli gene and is characterized by the development of hundreds of colorectal adenomas and, eventually, colorectal cancer. Nonsteroidal antiinflammatory drugs can cause regression of adenomas, but whether they can prevent adenomas is unknown. Methods: We conducted a randomized, doubleblind, placebo-controlled study of 41 young subjects (age range, 8 to 25 years) who were genotypically affected with familial adenomatous polyposis but phenotypically unaffected. The subjects received either 75 or 150 mg of sulindac orally twice a day or identical-appearing placebo tablets for 48 months. The number and size of new adenomas and side effects of therapy were evaluated every four months for four years, and the levels of five major prostaglandins were serially measured in biopsy specimens of normal-appearing colorectal mucosa. Results: After four years of treatment, the average rate of compliance exceeded 76 percent in the sulindac group, and mucosal prostaglandin levels were lower in this group than in the placebo group. During the course of the study, adenomas developed in 9 of 21 subjects (43 percent) in the sulindac group and 11 of 20 subjects in the placebo group (55 percent) (P=0.54). There were no significant differences in the mean number (P=0.69) or size (P=0.17) of polyps between the groups. Sulindac did not slow the development of adenomas, according to an evaluation involving linear longitudinal methods. Conclusions: Standard doses of sulindac did not prevent the development of adenomas in subjects with familial adenomatous polyposis.

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