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Clinical Trial Results

Summaries of Newsworthy Clinical Trial Results
  • Posted: 04/23/2008
  • Updated: 05/21/2009

Celecoxib Reduces Risk of Precancerous Colorectal Polyps: Five-Year Results of APC Trial

Adapted from the NCI Cancer Bulletin.

The five-year results of the Adenoma Prevention with Celecoxib (APC) trial indicate that two years after daily use of celecoxib (Celebrex®) has ended, there continues to be a modest reduction in the recurrence of colorectal polyps.

Initially presented at the 2006 AACR annual meeting, the trial's results showed that compared with placebo, adenoma recurrence and advanced adenoma recurrence were significantly reduced in participants who took celecoxib daily for three years. Participants, all of whom had previously had lesions removed, had significantly fewer total adenomas and advanced adenomas at three years.

Speaking at the 2008 AACR annual meeting in San Diego, Calif., the trial's lead investigator, Dr. Monica Bertagnolli, reported that although the effect diminished after the drug was discontinued, a treatment benefit was still present at five years. Celecoxib use, however, was associated with an increased risk of serious side effects, including heart attacks and strokes. The safety analysis suggests that these serious adverse events were greatest in participants with pre-existing cardiovascular risk factors. (The results were subsequently published in the April 2009 issue of Cancer Prevention Research; see the journal abstract.)

Overall, compared with participants in the placebo arm, advanced adenoma risk was reduced by 41 percent among patients taking the 400 mg/day dose and 26 percent among patients taking the 800 mg/day dose.

Cardiovascular events were far more likely among participants who had at least two pre-existing cardiovascular risk factors (e.g., high blood pressure, diabetes, age of more than 65 years) at study entry: 5.9 percent of participants in the placebo arm, compared with 8.2 percent in the 400 mg/day arm and 11.2 percent in the 800 mg/day arm, reported a cardiovascular adverse event.

By contrast, for APC participants who had no cardiovascular risk factors at study entry, the rates of cardiovascular adverse events were 0.9 percent, 3.9 percent, and 1.9 percent, respectively.

The results, said Dr. Bertagnolli, of Brigham and Women's Hospital in Boston, Mass., demonstrate that COX-2 inhibitors such as celecoxib "are risky for some patients." But, she continued: "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."

These results come on the heels of a more extensive, National Cancer Institute-funded cross-study safety analysis of six placebo-controlled studies involving celecoxib. These data were presented in late March 2008 at the annual meeting of the American College of Cardiology. That analysis showed a threefold increased risk of cardiovascular events in patients given the highest celecoxib dose, but also showed that risk was significantly higher among study participants with underlying cardiovascular risk factors.

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