Journal
AMERICAN JOURNAL OF GASTROENTEROLOGY
Volume 105, Issue 6, Pages 1437-1443Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ajg.2009.758
Keywords
-
Categories
Funding
- NCI/NIH [N01-CN-05126-02]
- Pfizer Inc
- Division of Cancer Prevention, National Cancer Institute, Bethesda, MD
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available