The Safety and Efficacy of Celecoxib in Children With... : Official journal of the American College of Gastroenterology | ACG (original) (raw)

ORIGINAL CONTRIBUTIONS: PEDIATRICS

The Safety and Efficacy of Celecoxib in Children With Familial Adenomatous Polyposis

Lynch, Patrick M MD, JD1; Ayers, Gregory D MS2; Hawk, Ernie MD, MPH3; Richmond, Ellen RN, MSN3; Eagle, Craig MD4; Woloj, Mabel PhD4; Church, James MD5; Hasson, Hennie RN6; Patterson, Sherri RN7; Half, Elizabeth MD8; Burke, Carol A MD8

1Department of Gastroenterology, Hepatology and Nutrition, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

2Department of Biostatistics, Vanderbilt-Ingram Cancer Center, Cancer Biostatistics Center, Nashville, Tennessee, USA

3Gastrointestinal and Other Cancers Research Group, Division of Cancer Prevention, The National Cancer Institute, Bethesda, Maryland, USA

4Pfizer Inc., New York, New York, USA

5Department of Colorectal Surgery, Cleveland Clinic, Cleveland, Ohio, USA

6Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio, USA

7Division of Cancer Prevention and Population Sciences, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

8Department of Gastroenterology and Hepatology, Prevention and Familial Cancer Service, Meir Medical Cancer Center, Kfar Saba, Israel

Correspondence: Patrick M. Lynch, Department of Gastroenterology, Hepatology and Nutrition 436, The University of Texas M.D. Anderson Cancer Center, P.O. Box 301402, Houston, Texas 77230-1402, USA. E-mail: [email protected]

published online 16 March 2010

Received 31 July 2009; accepted 2 December 2009

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.