Celecoxib protects against colorectal adenoma 2 years out

Celecoxib reduced the incidence of advanced colorectal adenomas by 41% in 5 years among high-risk patients who took the controversial COX-2 inhibitor for 3 years in a cancer prevention trial before stopping it because of cardiovascular safety concerns.

Even 2 years after we discontinued treatment with celecoxib, our patients still derived a considerable chemoprective benefit.

Just as notably reported celecoxib was shown to be safe in patients who had no underlying risk factors for cardiovascular disease when they entered the study.

The Adenoma Prevention with Celecoxib (APC) trial, which began enrolling patients in 1999 and was planned to run for a total of 5 years of drug treatment, the study was designed to test the efficacy and safety of two doses of celecoxib in preventing colorectal adenomas in 2,035 individuals at high risk for colon cancer.

Patients who had adenomas removed before study entry were assigned to placebo (679 patients), 200mg twice a day of celecoxib (685), or 400mg twice a day (671) of celecoxib. They were followed with colonoscopies performed at 1 and 3 years. Just as the last patients completed 3 years of the study, the investigators recognized increased cardiovascular toxicity with celecoxib and discontinued the drug in all patients.

At the time they began study, the cardiovascular toxicity of celecoxib was not known. In fact, this study was the first to unveil cardiovascular disease risk with the drug. So they did not screen any of study population for cardiovascular risk factors. Most of patients — 84% whose media age was 60 at the time of study entry, had at least one risk factor.

The efficacy results at the 3-year point were impressive. Sixty percent of the placebo group had a new adenomas, compared with 43% of patients receiving 200mg of celecoxib twice a day, and 38% of those in the high-dose group receiving 400mg twice a day. The reduction in the rate of new advanced adenomas was even more striking, with a 64% reduction at the 400mg dose and a 55% reduction at the 200mg dose of celecoxib.

Although the patients discontinued celecoxib and colleagues decided to continue the trial as an observational study. Approximately one-third of the original randomized cohort had a colonoscopy at 5 years as planned.

At 5 years, with no drug on board for 1.5-2 years, the reduction in advanced lesions was 41% in the cohort who received the lower dose of celecoxib and 26% in patients who received the higher dose. There was no rebound effect — that is, lesions did not suddenly appear when the drug was stopped.