In a randomized clinical chemoprevention trial, a combination of celecoxib and diflouromethylornithine resulted in a nonsignificant benefit among patients with familial adenomatous polyposis when adenoma count in a defined area was used as the primary endpoint. However, the combination was well tolerated, and a secondary measure of adenoma burden using a video-based global assessment showed a significant incremental benefit.
Researchers enrolled patients from the University of Texas MD Anderson Cancer Center Hereditary Colorectal Cancer Registry, the Cleveland Clinic David G. Jagelman Inherited Colon Cancer Registry, the St. Mark’s Hospital Polyposis Registry, UK, and from outside referrals. All 112 patients (60 men, 52 women) had familial adenomatous polyposis (FAP). The patients were aged 18 to 65 years and the mean age was 38 years.
Between December 2001 and August 2008, patients were randomly assigned to celecoxib (CXB) and diflouromethylornithine (DFMO) combined, or celecoxib alone. Researchers measured the percentage change in adenoma count in a defined field for the primary endpoint; adenoma burden weighted by adenoma diameter and video review of entire colon/rectal segments were secondary endpoints.
Of the 112 patients, 89 had landmark-matched polyp counts recorded at baseline and at 6 months follow-up. For these patients, the mean percentage change in adenoma count at the end of the 6 months was – 13% for patients prescribed CXB combined with DFMO, compared with – 1% for patients prescribed CXB alone (P = .69).
For adenoma burden, the mean percentage change at 6 months was – 40% for the patients prescribed CXB combined with DFMO, compared with – 27% for the patients prescribed CXB alone (P = .13). Patients in the CXB-only group experienced more fatigue than the patients prescribed the combination (P = .02). Fatigue was the only significant adverse event found.
“The combination of CXB and DFMO, in the doses employed, is well tolerated by this mainly young patient population. Hearing loss does not seem to be an issue clinically or audiometrically,” the researchers wrote. “The efficacy of this combination appears marginal to substantial, depending on how the effect is measured. In the future, careful attention to the means used to measure response may be as or more important than the agent(s) employed. This will be especially the case if a measure of ‘clinical benefit’ is insisted upon, as seems evident from FDA pronouncements.”
Disclosures: The researchers report no relevant financial disclosures.