By Bruce Sylvester
SAN DIEGO -- May 20, 2008 -- Celecoxib therapy appears to reduce the incidence and recurrence of colorectal adenoma, researchers reported here at Digestive Diseases Week 2008 (DDW).
"After 3 years on treatment and 2 years off, the prophylactic effect is still evident in the prevention of polyp recurrence," said lead investigator Nadir Arber, MD, Director, Integrated Cancer Prevention Center, Tel Aviv Medical Center, Tel Aviv University, Tel Aviv, Israel, in a media briefing on May 18.
Colon cancer is associated with a high rate of mortality and screening is underutilised, so more options for prevention are needed, according to Dr. Arber and his colleagues.
To determine the effects of chemopreventive therapy on the incidence of colorectal adenoma, the researchers conducted an international 3-year, randomised, placebo-controlled, double-blind study.
Initially, the investigators followed 1,561 patients at high risk of colorectal adenoma who were treated with a single celecoxib dose daily of 400 mg (twice the approved dose for osteoarthritis pain) or daily placebo and were evaluated for rates of benign polyps.
After 3 years of treatment, subjects randomised to celecoxib 400 mg daily achieved a relative risk (RR) of new adenomatous polyps of 0.64 (P < 0.001; 95% confidence interval [CI], 0.56-0.75) and of advanced adenomatous polyps of 0.49 (P < .001; 95% CI, 0.33-0.73).
The trial was halted at year 3. The authors noted, "When concerns over cardiovascular risk prompted cessation of drug administration, based on results from another adenoma prevention study, 1,043 subjects were given the option to continue safety assessments for at least 2 years after treatment ended and undergo a final colonoscopy at year 5."
In the newly reported analysis, they found that the cumulative 5-year detection rate for adenomatous polyps and the detection rate for advanced adenomatous polyps were lower in the celecoxib 400-mg daily group (51.4% vs 57.5%, P < .0001; RR, 0.75; 95% CI, 0.65-0.86).
For advanced adenomatous polyps, the detection rate was 10% in the celecoxib group and 13.8% in the placebo group (P = .0072; RR, 0.64; 95% CI, 0.457-0.887).
The researchers noted that the proportion of subjects with new adenomatous polyps at year 5 was higher in the celecoxib cohort than in the placebo cohort (27% vs 16%, P < .0001).
Over the 5 years of the study, cardiac disorders occurred in 10.4% of subjects randomised to celecoxib 400 mg and in 6.5% of placebo subjects.
In the 2 years off-treatment, there were very few reported serious cardiac disorders (1.4% celecoxib vs 1% placebo).
Over the 5 years of the study, subjects treated with celecoxib 400 mg had a slightly higher rate of adverse events compared with placebo (77.9% vs 75.4%) and serious adverse events (23.9% vs 20.6%).
"We conclude that 2 years on average after drug administration was discontinued, subjects in the celecoxib group sustained a cumulative lower relative risk of detection of any adenomas and, in particular, those considered advanced," the researchers concluded.
Dr. Arber added, "We know that celecoxib reduces the incidence and recurrence of adenoma. But cardiotoxicity is still a concern and requires more study."
Along with its other indications, celecoxib is currently approved by the US Food and Drug Administration as an adjunctive treatment for patients with familial adenomatous polyposis (FAP).
[Presentation title: Chemopreventive Effectiveness of Celecoxib Two Years After Cessation of Treatment.]
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