In this three-year study, presented today at Digestive Disease Week 2008 (R), investigators sought to determine if the use of a chemopreventive drug could reduce adenoma burden.

Unless detected early, the mortality rate for colon cancer is high. With colon cancer screening rates only at about 30 per cent in the US, additional options to prevent colon cancer are eagerly sought. In this three-year, randomized, placebo-controlled, double-blind study, investigators sought to determine if the use of a chemopreventive drug could reduce adenoma (benign tumor) burden.

The study followed 1,561 adenoma-prone patients in 32 countries to determine if patients treated with a single 400-mg daily dose of celecoxib (twice the approved osteoarthritis dose) had lower rates of benign polyps than those treated with a placebo. Celecoxib has previously demonstrated efficacy in preventing adenomatous polyp recurrence, however, questions have been raised about the cardiac profile of celecoxib and other common prescription arthritis pain relievers.

For those randomized to celecoxib, 400 mg daily, relative risk (RR) of new adenomatous polyp was 0.64 (95 per cent confidence interval [CI], 0.56–0.75); p < 0.001) and that for advanced adenomatous polyp was 0.49 (95 per cent CI, 0.33–0.73; p < 0.001) through year three compared with placebo.

Additionally, no statistically significant difference was found in the rate of side effects between the two groups at year three. 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 two years after treatment ended and undergo a final colonoscopy at year five.

Overall, the cumulative five-year rate of detecting any adenomatous polyp and that of detecting advanced adenomatous polyp were lower in the celecoxib 400 mg daily group (RR, 0.75; 95 per cent CI, 0.65–0.86; p < 0.0001), and that for advanced adenomatous polyp detection was 10 per cent in the celecoxib group and 13.8 per cent in the placebo group (RR, 0.64; 95 per cent CI, 0.457–0.887; p = 0.0072). However, the proportion of subjects with new adenomatous polyp, at year five only, was higher in the celecoxib group.

Over the five years of the study, including approximately three years on treatment and two years off treatment, cardiac disorders occurred in 10.4 per cent of patients randomized to celecoxib 400 mg and in 6.5 per cent of those randomized to placebo. In the two years off treatment very few serious cardiac disorders occurred (1 per cent placebo, 1.4 per cent celecoxib). Subjects who received celecoxib 400 mg experienced a slightly higher rate of adverse (77.9 per cent vs. 75.4 per cent for placebo) and serious adverse events (23.9 per cent vs. 20.6 for placebo) over the five-year study period.

These data, together with additional new placebo-controlled analyses of celecoxib cardiovascular safety, suggest that chemoprevention with celecoxib may be safe and effective for some high risk colorectal adenoma patients with low cardiovascular risk.

"We know the drug is effective to reduce the incidence and recurrence of adenoma," said Nadir Arber, MD, head of the Integrated Cancer Prevention Center at Tel Aviv Medical Center, Tel Aviv University, Israel. "However, advances are needed to either use the drug in lower doses or develop combination therapy that can produce the same effect without the adverse side effects."

TrackBack URI for this entry

Comments (0)

Subscribe to this comment's feed