The safety and efficacy of celecoxib in children with familial adenomatous
polyposis.
Author(s): Lynch PM, Ayers GD, Hawk E, Richmond E, Eagle C, Woloj M, Church J, Hasson H,
Patterson S, Half E, Burke CA.
Affiliation(s): Department of Gastroenterology, Hepatology and Nutrition, University of Texas
M.D. Anderson Cancer Center, Houston, Texas 77230-1402, USA.
plynch@mdanderson.org
Publication date & source: 2010, Am J Gastroenterol. , 105(6):1437-43
OBJECTIVES: Celecoxib is approved as an adjunctive chemopreventive agent in
adults with familial adenomatous polyposis (FAP). Its safety and efficacy for
colorectal polyps in children is unknown. We evaluated the short-term (3 months)
safety and preliminary efficacy of celecoxib in children with FAP.
METHODS: This was a phase I, dose-escalation trial, with three successive cohorts
of six children. Children of ages 10-14 years with APC gene mutations and/or
adenomas with a family history of FAP were studied at M.D. Anderson Cancer Center
and the Cleveland Clinic. Colonoscopy was performed at baseline and month 3.
Random assignment was in a 2:1 generic:placebo ratio, escalating from cohort 1 (4
mg/kg/day) to cohort 2 (8 mg/kg/day) to cohort 3 (16 mg/kg/day). Adherence and
adverse event (AE) monitoring was conducted at 2-week intervals during drug
administration. Safety profile, difference in number, and percent change in
colorectal polyps were compared among the four treatments (placebo and the three
dose-escalation groups).
RESULTS: Eighteen subjects completed drug dosing and both colonoscopies. Median
age was 12.3 years (56% female). No clinically meaningful differences in AEs were
seen between placebo subjects and subjects at any of the three celecoxib doses.
Median polyp count at baseline was 31. There was a 39.1% increase in the number
of polyps in placebo subjects at month 3, whereas in the highest dose celecoxib
group, 16 mg/kg/day, a 44.2% reduction was seen (P=0.01).
CONCLUSIONS: Celecoxib at a dose of 16 mg/kg/day, corresponding to the adult dose
of 400 mg BID, is safe, well tolerated, and significantly reduced the number of
colorectal polyps in children with FAP.
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