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An international randomised trial of celecoxib versus celecoxib plus difluoromethylornithine in patients with familial adenomatous polyposis
  1. Patrick M Lynch1,
  2. Carol A Burke2,
  3. Robin Phillips3,
  4. Jeffrey S Morris4,
  5. Rebecca Slack4,
  6. Xuemei Wang4,
  7. Jun Liu5,
  8. Sherri Patterson6,
  9. Frank A Sinicrope7,
  10. Miguel A Rodriguez-Bigas8,
  11. Elizabeth Half9,
  12. Steffen Bulow10,
  13. Andrew Latchford3,
  14. Sue Clark3,
  15. William A Ross1,
  16. Bonnie Malone1,
  17. Hennie Hasson2,
  18. Ellen Richmond11,
  19. Ernest Hawk12
  1. 1Department of Gastroenterology, Hepatology and Nutrition, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
  2. 2Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio, USA
  3. 3The Polyposis Registry, St. Mark's Hospital, London, UK
  4. 4Division of Quantitative Sciences, Department of Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
  5. 5Department of Plastic Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
  6. 6Department of Cancer Prevention and Pop Science, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
  7. 7Division of Gastroenterology, Hepatology and Oncology, Mayo Clinic, Rochester, Minnesota, USA
  8. 8Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
  9. 9Gatroenterology Department, Rambam Medical Center, Haifa, Israel
  10. 10Hvidore Hospital, Denmark, UK
  11. 11Gastrointestinal and Other Cancers Research Group, Division of Cancer Prevention, The National Cancer Institute, Bethesda, Maryland, USA
  12. 12Division of OVP, Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  1. Correspondence to Dr Patrick M Lynch, Department of Gastroenterology, Hepatology and Nutrition 1466, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030-4009, USA; plynch{at}


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 number N01-CN95040.


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