Document Detail


The safety and efficacy of celecoxib in children with familial adenomatous polyposis.
MedLine Citation:
PMID:  20234350     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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
Publication Detail:
Type:  Clinical Trial, Phase I; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, N.I.H., Extramural     Date:  2010-03-16
Journal Detail:
Title:  The American journal of gastroenterology     Volume:  105     ISSN:  1572-0241     ISO Abbreviation:  Am. J. Gastroenterol.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-06-04     Completed Date:  2010-07-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0421030     Medline TA:  Am J Gastroenterol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1437-43     Citation Subset:  IM    
Affiliation:
Department of Gastroenterology, Hepatology and Nutrition, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77230-1402, USA. plynch@mdanderson.org
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MeSH Terms
Descriptor/Qualifier:
Adenoma / diagnosis,  prevention & control*
Adenomatous Polyposis Coli / diagnosis,  drug therapy*
Adolescent
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
Grant Support
ID/Acronym/Agency:
N01-CN-05126-02/CN/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Cyclooxygenase 2 Inhibitors; 0/Pyrazoles; 0/Sulfonamides; 169590-42-5/celecoxib

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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