RT Journal Article
SR Electronic
T1 An international randomised trial of celecoxib versus celecoxib plus difluoromethylornithine in patients with familial adenomatous polyposis
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 286
OP 295
DO 10.1136/gutjnl-2014-307235
VO 65
IS 2
A1 Patrick M Lynch
A1 Carol A Burke
A1 Robin Phillips
A1 Jeffrey S Morris
A1 Rebecca Slack
A1 Xuemei Wang
A1 Jun Liu
A1 Sherri Patterson
A1 Frank A Sinicrope
A1 Miguel A Rodriguez-Bigas
A1 Elizabeth Half
A1 Steffen Bulow
A1 Andrew Latchford
A1 Sue Clark
A1 William A Ross
A1 Bonnie Malone
A1 Hennie Hasson
A1 Ellen Richmond
A1 Ernest Hawk
YR 2016
UL http://gut.bmj.com/content/65/2/286.abstract
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.