title: Primary chemoprevention of familial adenomatous polyposis with sulindac.
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, double-blind, 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.
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, USA.
authors.forename: Francis M
authors.initials: FM
authors.lastname: Giardiello
authors.forename: Vincent W
authors.initials: VW
authors.lastname: Yang
authors.forename: Linda M
authors.initials: LM
authors.lastname: Hylind
authors.forename: Anne J
authors.initials: AJ
authors.lastname: Krush
authors.forename: Gloria M
authors.initials: GM
authors.lastname: Petersen
authors.forename: Jill D
authors.initials: JD
authors.lastname: Trimbath
authors.forename: Steven
authors.initials: S
authors.lastname: Piantadosi
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Garrett
authors.forename: Deborah E
authors.initials: DE
authors.lastname: Geiman
authors.forename: Walter
authors.initials: W
authors.lastname: Hubbard
authors.forename: G Johan A
authors.initials: GJ
authors.lastname: Offerhaus
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Hamilton
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics / Q000517:prevention & control*; D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D002648:Child; D004311:Double-Blind Method; D005260:Female; D017491:Genes, APC; D006801:Humans; D008297:Male; D009154:Mutation; D010349:Patient Compliance; D011453:Prostaglandins / Q000032:analysis; D012007:Rectum / Q000737:chemistry / Q000473:pathology; D012044:Regression Analysis; D013467:Sulindac / Q000009:adverse effects / Q000627:therapeutic use*; D013929:Thromboxane B2 / Q000032:analysis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D011453:Prostaglandins; D013467:Sulindac; D013929:Thromboxane B2