An international randomised trial of celecoxib versus celecoxib plus difluoromethylornithine in patients with familial adenomatous polyposis

Gut
Patrick M LynchErnest T Hawk

Abstract

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. 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. 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). CXB combined with DFMO yielded moderate synergy according to a video-based global assessment. No significant difference in adenoma ...Continue Reading

References

Aug 9, 1991·Science·K W KinzlerD McKechnie
Jan 1, 1997·Abdominal Imaging·F L Lanza
May 30, 1998·Gastroenterology·R A Gupta, R N DuBois
Jun 30, 2000·The New England Journal of Medicine·G SteinbachG Kelloff
Nov 25, 2003·Digestive Diseases and Sciences·A HallakN Arber
Feb 17, 2005·The New England Journal of Medicine·Robert S BresalierUNKNOWN Adenomatous Polyp Prevention on Vioxx (APPROVe) Trial Investigators
Feb 17, 2005·The New England Journal of Medicine·Scott D SolomonUNKNOWN Adenoma Prevention with Celecoxib (APC) Study Investigators
Sep 1, 2006·The New England Journal of Medicine·Monica M BertagnolliUNKNOWN APC Study Investigators
Sep 1, 2006·The New England Journal of Medicine·Nadir ArberUNKNOWN PreSAP Trial Investigators
Nov 8, 2006·Gastroenterology·John A BaronUNKNOWN APPROVe Trial Investigators

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Citations

Jan 16, 2016·Gastrointestinal Endoscopy·Patrick M LynchGabriela Moeslein
Jun 17, 2016·Molecular & Cellular Oncology·John Inge JohnsenNinib Baryawno
Apr 17, 2016·Familial Cancer·Patrick M Lynch
Apr 21, 2016·Nature Reviews. Gastroenterology & Hepatology·Luigi RicciardielloPatrick M Lynch
Jan 28, 2017·Future Oncology·George A AlexiouAthanassios P Kyritsis
Oct 26, 2018·The Journal of Biological Chemistry·Eugene W GernerAlfred Cohen
Dec 27, 2018·Journal of Pediatric Gastroenterology and Nutrition·Warren HyerAndrew Latchford
Jul 10, 2019·International Journal of Cancer. Journal International Du Cancer·Revital KarivRina Rosin-Arbesfeld
Jun 9, 2020·Familial Cancer·Phillip M Kemp BohanCarol A Burke
Sep 10, 2020·The New England Journal of Medicine·Carol A BurkeAlfred Cohen
Aug 12, 2018·International Journal of Molecular Sciences·Altaf MohammedChinthalapally V Rao
Jun 9, 2020·Hospital Pharmacy·Oumer SadaMensur Shafi
Sep 26, 2020·Frontiers in Pharmacology·Wen TianStanley G Rockson
Dec 15, 2017·PloS One·Hong Im KimJohn I Risinger
Jul 2, 2020·Cancer Management and Research·Xiangjie FuPeijun Liu
Jan 21, 2017·Oncology Letters·Jun YangJian Dong
May 9, 2019·Cancer Research·Lisa KaminskiFrédéric Bost
Sep 30, 2019·Gastroenterology·Bryson W Katona, Jennifer M Weiss
Dec 10, 2020·Cancer Cell International·Jiajing LiYuxin Sun
Apr 14, 2020·European Journal of Medicinal Chemistry·Thanigaimalai PillaiyarMurugesan Sankaranarayanan
Apr 5, 2021·The Lancet. Gastroenterology & Hepatology·Patrick M Lynch
Jul 3, 2021·Current Treatment Options in Gastroenterology·Michael J Hall
Jul 17, 2021·Oncology Reviews·Olivia NoeJohn Nemunaitis
Oct 1, 2021·Drug Discovery Today·Diana Duarte, Nuno Vale

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