title: A dose-finding study of aspirin for chemoprevention utilizing rectal mucosal prostaglandin E(2) levels as a biomarker.
abstract: Epidemiological and experimental evidence indicates that aspirin can protect against colorectal cancer. Aspirin inhibits cyclooxygenase enzymes and blocks prostaglandin (PG) biosynthesis. Using rectal PGE(2) levels as a mucosal biomarker, we sought to determine the optimal aspirin dose that would significantly suppress PGE(2) levels for chemoprevention trials. We conducted a randomized, double-blinded study in 60 subjects with prior sporadic colorectal adenoma(s) and evaluated three aspirin doses (81, 325, and 650 mg) or placebo taken daily for 4 weeks. PGE(2) levels in rectal biopsies performed at baseline and week 4 were analyzed by competitive immunoassay. Plasma salicylate levels, pill counts, and subject calendars were used to assess compliance. The 81-mg aspirin dose significantly suppressed PGE(2) levels relative to placebo (P = 0.005) and did so to an equivalent extent as did higher doses (P > 0.4) in evaluable subjects (n = 55) over a 4-week treatment period. Serum salicylate levels were associated with aspirin dose (P = 0.0002). Pill counts and calendars indicated that >98% of doses were taken by all subjects. No adverse events occurred in this short-term study. The 81-mg daily aspirin dose suppressed PGE(2) levels to an equivalent extent as did the 650-mg dose and supports the use of this dose for chemoprevention trials.
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Dory
authors.initials: D
authors.lastname: Sample
authors.forename: Michael
authors.initials: M
authors.lastname: Wargovich
authors.forename: Susan M
authors.initials: SM
authors.lastname: Fischer
authors.forename: Nikil
authors.initials: N
authors.lastname: Inamdar
authors.forename: Peter
authors.initials: P
authors.lastname: Schwartz
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wang
authors.forename: Kim-Anh
authors.initials: KA
authors.lastname: Do
authors.forename: Frank A
authors.initials: FA
authors.lastname: Sinicrope
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000008:administration & dosage*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018890:Chemoprevention / Q000379:methods; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000517:prevention & control*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D015232:Dinoprostone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
chemical_list: D014408:Biomarkers, Tumor; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone; D001241:Aspirin