Colon adenoma prevention with celecoxib, a non-steroidal anti-inflammatory drug (NSAID), is effective and can be safe for patients without underlying cardiovascular risk factors, according to five-year data of a randomized phase III trial.
"There has been a significant amount of negative press about Cox-2 inhibitors including celecoxib, and clearly these drugs are risky for some patients. However, our study also shows that for patients without major cardiovascular risk factors, celecoxib at low doses protects against high-risk lesions that can lead to colon cancer," said Monica Bertagnolli, M.D., associate professor of surgery at the Brigham and Women's Hospital.
Bertagnolli was the lead researcher on the Adenoma Prevention with Celecoxib (APC) trial, which enrolled 2,035 patients and randomly assigned them to 200 mg twice-daily (400 mg) of celecoxib, 400 mg twice-daily (800 mg) of celecoxib or a placebo group.
At three years, patients taking celecoxib at 400 mg had a 29 percent reduction in adenomas, a precursor to colon cancer, while those taking 800 mg had a 38 percent reduction. Advanced adenomas, which are lesions with a high-risk for cancer development, were reduced by 55 percent with 400 mg and 63 percent with 800 mg.
After three years, patients stopped taking celecoxib and were followed for another two years to assess safety and effectiveness. Even after two years off medication, the five-year rate of advanced adenoma was reduced by 41 percent among patients taking the lower dose and 26 percent among patients taking the higher dose.
Cardiovascular events were more common in patients taking celecoxib, with a rate of 3.8 percent among those patients taking placebo to 6 percent among the low dose group and 7.5 percent among the high dose group. However, when researchers looked at factors that might predict cardiovascular complications, they found a much different story.
For patients with no cardiovascular risk factors before using celecoxib, the rate of cardiovascular adverse events was 0.9 percent in the placebo group, 3.9 percent in the 400 mg group and 1.9 percent in the high dose group. Cardiovascular risk factors included smoking, high cholesterol, high blood pressure, diabetes, presence of atherosclerosis and age over 65.
If a patient had one risk factor, the risk was 2.2 percent in the placebo group, 3.7 percent in the 400 mg dose group and 4.9 percent in the high dose group.
The greater cardiovascular risk was observed among patients who had at least two cardiovascular risk factors at the time they entered the study, where the placebo group had a 5.9 percent risk, the 400 mg group had an 8.2 percent risk and the 800 mg group had an 11.2 percent risk.
"This new data allows us to carefully select patients who can benefit from this drug," Bertagnolli said. "Although it should be used with caution, those patients with a high risk for colon cancer and a low risk for cardiovascular disease are going to receive significant benefit."
This research was presented at the 2008 Annual Meeting of the American Association for Cancer Research, April 12-16, 2008.
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