The safety and efficacy of celecoxib in children with familial adenomatous polyposis.

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.