title: An international randomised trial of celecoxib versus celecoxib plus difluoromethylornithine in patients with familial adenomatous polyposis.
abstract: OBJECTIVE
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov number N01-CN95040.
authors: Department of Gastroenterology, Hepatology and Nutrition, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors: Patrick M
authors: PM
authors: Lynch
authors: Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio, USA.
authors: Carol A
authors: CA
authors: Burke
authors: The Polyposis Registry, St. Mark's Hospital, London, UK.
authors: Robin
authors: R
authors: Phillips
authors: Division of Quantitative Sciences, Department of Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors: Jeffrey S
authors: JS
authors: Morris
authors: Division of Quantitative Sciences, Department of Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors: Rebecca
authors: R
authors: Slack
authors: Division of Quantitative Sciences, Department of Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors: Xuemei
authors: X
authors: Wang
authors: Department of Plastic Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors: Jun
authors: J
authors: Liu
authors: Department of Cancer Prevention and Pop Science, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors: Sherri
authors: S
authors: Patterson
authors: Division of Gastroenterology, Hepatology and Oncology, Mayo Clinic, Rochester, Minnesota, USA.
authors: Frank A
authors: FA
authors: Sinicrope
authors: Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors: Miguel A
authors: MA
authors: Rodriguez-Bigas
authors: Gatroenterology Department, Rambam Medical Center, Haifa, Israel.
authors: Elizabeth
authors: E
authors: Half
authors: Hvidore Hospital, Denmark, UK.
authors: Steffen
authors: S
authors: Bulow
authors: The Polyposis Registry, St. Mark's Hospital, London, UK.
authors: Andrew
authors: A
authors: Latchford
authors: The Polyposis Registry, St. Mark's Hospital, London, UK.
authors: Sue
authors: S
authors: Clark
authors: Department of Gastroenterology, Hepatology and Nutrition, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors: William A
authors: WA
authors: Ross
authors: Department of Gastroenterology, Hepatology and Nutrition, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors: Bonnie
authors: B
authors: Malone
authors: Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio, USA.
authors: Hennie
authors: H
authors: Hasson
authors: Gastrointestinal and Other Cancers Research Group, Division of Cancer Prevention, The National Cancer Institute, Bethesda, Maryland, USA.
authors: Ellen
authors: E
authors: Richmond
authors: Division of OVP, Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: Ernest
authors: E
authors: Hawk
mesh_terms: D018256:Adenomatous Polyps / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068579:Celecoxib / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D000518:Eflornithine / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012812:Sigmoidoscopy; D047368:Tumor Burden; D055815:Young Adult
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D000068579:Celecoxib; D000518:Eflornithine
keywords: ADENOMA; CANCER; CHEMOPREVENTION; FAMILIAL ADENOMATOUS POLYPOSIS; POLYP