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

Abstract

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: Patrick M Lynch, Gregory D Ayers, Ernie Hawk, Ellen Richmond, Craig Eagle, Mabel Woloj, James Church, Hennie Hasson, Sherri Patterson, Elizabeth Half, Carol A Burke
• Journal: The American journal of gastroenterology (Am J Gastroenterol) Vol. 105 Issue 6 Pg. 1437-43 (Jun 2010) ISSN: 1572-0241 [Electronic] United States
• PMID: 20234350 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural)

Chemical References

• Cyclooxygenase 2 Inhibitors
• Pyrazoles
• Sulfonamides
• Celecoxib

Topics

• Adenoma (diagnosis, prevention & control)
• Adenomatous Polyposis Coli (diagnosis, drug therapy)
• Adolescent
• Celecoxib
• Child
• Cohort Studies
• Colonic Neoplasms (diagnosis, prevention & control)
• Colonic Polyps (diagnosis, prevention & control)
• Colonoscopy
• Cyclooxygenase 2 Inhibitors (therapeutic use)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Humans
• Male
• Pyrazoles (therapeutic use)
• Sulfonamides (therapeutic use)
• Treatment Outcome