In human and animal studies, nonsteroidal anti-inflammatory drugs have been associated with a reduced risk of colorectal neoplasia.
The underlying mechanisms are unknown, inhibition of cyclooxygenase (COX), particularly COX-2, is thought to play a role.
Dr John Baron and colleagues from New Hampshire conducted a randomized, placebo-controlled, double-blind trial.
The investigative team assessed whether use of the selective COX-2 inhibitor rofecoxib would reduce the risk of colorectal adenomas.
The investigators randomized 2587 subjects with a recent history of histologically confirmed adenomas to receive daily placebo or 25 mg rofecoxib.
|The chemopreventive effect was most pronounced in the first year|
Randomization was stratified by baseline use of cardioprotective aspirin.
The investigators planned colonoscopic follow-up evaluation for 1 and 3 years after randomization.
The primary end point was all adenomas diagnosed during 3 years of treatment.
In a modified intent-to-treat analysis, the investigators computed the relative risk of any adenoma after randomization.
The team used Mantel-Haenszel statistics stratified by low-dose aspirin use at baseline.
Adenoma recurrence was less frequent for rofecoxib subjects than for those randomized to placebo.
The investigators found that rofecoxib also conferred a reduction in risk of advanced adenomas.
The chemopreventive effect was more pronounced in the first year than in the subsequent 2 years.
The investigators noted that rofecoxib was associated with increased risks of upper gastrointestinal events, and serious thrombotic cardiovascular events.
Dr Baron's team concludes, “In this randomized trial, rofecoxib significantly reduced the risk of colorectal adenomas, but also had serious toxicity.”