2015/03/19 by Patrick M Lynch, Carol A. Burke, Robin Phillips +16 · 1 citation
Medicine · Biochemistry, Genetics and Molecular Biology · #Genetic factors in colorectal cancer #Inflammatory mediators and NSAID effects #Wnt/β-catenin signaling in development and cancer #Medicine #Adenoma #Clinical endpoint #Adverse effect #Celecoxib #Internal medicine #Familial adenomatous polyposis #Colorectal cancer #Randomized controlled trial #Gastroenterology #Surgery #Cancer
paper · doi:10.1136/gutjnl-2014-307235
openalex publication_date 2015/03/19 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/04
BACKGROUND AND AIM: Although Non-steroidal anti-inflammatory drugs reduce colorectal adenoma burden in familial adenomatous polyposis (FAP), the utility of combining chemopreventive agents in FAP is not known. We conducted a randomised trial of celecoxib (CXB) versus CXB+diflouromethylornithine (DFMO) to determine the synergistic effect, if any. METHODS: The primary endpoint was % change in adenoma count in a defined field. Secondary endpoints were adenoma burden (weighted by adenoma diameter) and video review of entire colon/rectal segments. Adverse event (AEs) were monitored by National Cancer Institution toxicity criteria. RESULTS: 112 subjects were randomised: 60 men and 52 women at a mean age of 38 years. For the 89 patients who had landmark-matched polyp counts available at baseline and 6 months, the mean % change in adenoma count over the 6 months of trial was -13.0% for CXB+DFMO and -1.0% for CXB (p=0.69). Mean % change in adenoma burden was -40% (CXB+DFMO) vs -27% (CXB) (p=0.13). Video-based global polyp change was -0.80 for CXB+DFMO vs -0.33 for CXB (p=0.03). Fatigue was the only significant AE, worse on the CXB arm (p=0.02). CONCLUSIONS: CXB combined with DFMO yielded moderate synergy according to a video-based global assessment. No significant difference in adenoma count, the primary endpoint, was seen between the two study arms. No evidence of DFMO-related ototoxicity was seen. There were no adverse cardiovascular outcomes in either trial arm and no significant increase in AEs in the CXB+DFMO arm of the trial. Differences in outcomes between primary and secondary endpoints may relate to sensitivity of the endpoint measures themselves. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number N01-CN95040.