Patrick M Lynch1, Carol A Burke2, Robin Phillips3, Jeffrey S Morris4, Rebecca Slack4, Xuemei Wang4, Jun Liu5, Sherri Patterson6, Frank A Sinicrope7, Miguel A Rodriguez-Bigas8, Elizabeth Half9, Steffen Bulow10, Andrew Latchford3, Sue Clark3, William A Ross1, Bonnie Malone1, Hennie Hasson2, Ellen Richmond11, Ernest Hawk12. 1. Department of Gastroenterology, Hepatology and Nutrition, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA. 2. Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio, USA. 3. The Polyposis Registry, St. Mark's Hospital, London, UK. 4. Division of Quantitative Sciences, Department of Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA. 5. Department of Plastic Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA. 6. Department of Cancer Prevention and Pop Science, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA. 7. Division of Gastroenterology, Hepatology and Oncology, Mayo Clinic, Rochester, Minnesota, USA. 8. Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA. 9. Gatroenterology Department, Rambam Medical Center, Haifa, Israel. 10. Hvidore Hospital, Denmark, UK. 11. Gastrointestinal and Other Cancers Research Group, Division of Cancer Prevention, The National Cancer Institute, Bethesda, Maryland, USA. 12. Division of OVP, Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Abstract
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
RCT Entities:
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Authors: Daniel Herzig; Karin Hardiman; Martin Weiser; Nancy You; Ian Paquette; Daniel L Feingold; Scott R Steele Journal: Dis Colon Rectum Date: 2017-09 Impact factor: 4.585