PT  - JOURNAL ARTICLE
AU  - Lynch, Patrick M
AU  - Burke, Carol A
AU  - Phillips, Robin
AU  - Morris, Jeffrey S
AU  - Slack, Rebecca
AU  - Wang, Xuemei
AU  - Liu, Jun
AU  - Patterson, Sherri
AU  - Sinicrope, Frank A
AU  - Rodriguez-Bigas, Miguel A
AU  - Half, Elizabeth
AU  - Bulow, Steffen
AU  - Latchford, Andrew
AU  - Clark, Sue
AU  - Ross, William A
AU  - Malone, Bonnie
AU  - Hasson, Hennie
AU  - Richmond, Ellen
AU  - Hawk, Ernest
TI  - An international randomised trial of celecoxib versus celecoxib plus difluoromethylornithine in patients with familial adenomatous polyposis
AID  - 10.1136/gutjnl-2014-307235
DP  - 2016 Feb 01
TA  - Gut
PG  - 286--295
VI  - 65
IP  - 2
4099  - http://gut.bmj.com/content/65/2/286.short
4100  - http://gut.bmj.com/content/65/2/286.full
SO  - Gut2016 Feb 01; 65
AB  - 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.