The safety and efficacy of celecoxib in children with familial adenomatous polyposis.
OBJECTIVE
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.
Lynch
Patrick M
PM
Department of Gastroenterology, Hepatology and Nutrition, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77230-1402, USA. plynch@mdanderson.org
Ayers
Gregory D
GD
Hawk
Ernie
E
Richmond
Ellen
E
Eagle
Craig
C
Woloj
Mabel
M
Church
James
J
Hasson
Hennie
H
Patterson
Sherri
S
Half
Elizabeth
E
Burke
Carol A
CA
D000236:Adenoma / Q000175:diagnosis / Q000517:prevention & control*; D011125:Adenomatous Polyposis Coli / Q000175:diagnosis / Q000188:drug therapy*; D000293:Adolescent; D000068579:Celecoxib; D002648:Child; D015331:Cohort Studies; D003110:Colonic Neoplasms / Q000175:diagnosis / Q000517:prevention & control*; D003111:Colonic Polyps / Q000175:diagnosis / Q000517:prevention & control*; D003113:Colonoscopy; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D011720:Pyrazoles / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome
D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib