OXFORD, England -- A moderately high daily dose of aspirin taken long term may reduce colorectal cancer risk, but gastroenterologists should be cautious about recommending it, researchers said.
OXFORD, England, May 11 -- A moderately high daily dose of aspirin taken long term may prevent colorectal cancer, but gastroenterologists are cautious about recommending it, researchers said.
Five years of a daily aspirin dose of 300 mg or higher reduced colorectal cancer occurrence 63% to 74%, reported Peter M. Rothwell, M.D., Ph.D., of the Radcliffe Infirmary here, and colleagues
The results of their 10- to 14-year follow-up of two large British trials support short-term observational studies measuring adenoma risk, they wrote in the May 12 issue of The Lancet.
But, the findings counter those of large, long-term studies of low dose aspirin, such as the Physicians' Health Study and the Women's Health Study.
The difference is likely because a higher dose is necessary to impact adenoma formation via the cyclo-oxygenase-2 (COX-2) pathway, wrote Andrew T. Chan, M.D., M.P.H., of the Massachusetts General Hospital in Boston, in an accompanying editorial.
"However, with the concerns about the potential risks of long-term aspirin use and the availability of alternative prevention strategies (eg, screening), these findings are not sufficient to warrant a recommendation for the general population to use aspirin for cancer prevention," Dr. Chan cautioned.
Dr. Rothwell and colleagues followed up on two British trials that started in the early 1980s.
The British Doctors Aspirin Trial originally included 5,139 male physicians randomized to 500 mg aspirin or no aspirin for five to six years. Participants were not blinded to treatment.
The U.K. Transient Ischemic Attack Aspirin Trial (UK-TIA) included 2,449 patients who'd had a recent TIA or minor ischemic stroke. Patients were randomized to 300 mg or 1,200 mg aspirin a day or a placebo for one to seven years depending on the date of randomization.
The investigators used national cancer registries to track colorectal cancer occurrence for a median of 23 years in both trials. Altogether, there were 215 colorectal cancer cases.
Among the pooled analysis findings:
•Any duration aspirin use in the trials reduced colorectal cancer occurrence (hazard ratio 0.74, 95% confidence interval 0.56 to 0.97, P=0.02).
•Five or more years of aspirin use reduced occurrence even more (HR 0.63, 95% CI 0.47 to 0.85, P=0.002).
•The effect appeared only after 10 years (HR 0.92 for the first nine years, P=0.73, versus 0.60 for years 10 to 19, P=0.007).
•The greatest benefit was seen after five or more years of aspirin use 10 to 14 years after randomization (HR 0.37, 95% CI 0.20 to 0.70, P=0.002), particularly for those who were compliant (HR 0.26, 95% CI 0.12 to 0.56, P=0.0002).
•There was no effect on non-colorectal cancer occurrence (HR 1.01, 95% CI 0.88 to 1.16, P=0.87).
The researchers noted, however, that there was no data on aspirin use after the trials ended and neither trial was designed to study colorectal cancer.
The researchers also did a systematic review of observational studies on the risk of colorectal cancer with aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs).
Among the 19 independent case-control studies included, most found less aspirin or NSAID use among patients who developed colorectal cancer (pooled odds ratio 0.80, 95% CI 0.73 to 0.87, P<0.0001).
As in the randomized trials, the literature review showed increasing benefit for longer and more frequent use.
Irregular or occasional aspirin or NSAID use conferred no benefit (OR 1.01, 95% CI 0.93 to 1.09, P=0.87). Odds ratios were 0.79 for short-term aspirin use defined as less than five or 10 years, 0.69 for five or more or 10 or more years of therapy, and 0.60 for 10 or more years of regular use.
Together, the findings suggest aspirin is effective in primary prevention of colorectal cancer, the investigators concluded.
"Use of 300 mg or more of aspirin a day for about five years is effective in primary prevention of colorectal cancer, with a latency of about 10 years, which is consistent with findings from observational studies," they wrote.
If high oral aspirin doses are necessary for this benefit, "further research on the direct local effects of low dose colonic-release preparations might be worthwhile," Dr. Rothwell wrote.
While the cardiovascular and colorectal cancer benefits of aspirin may outweigh risk of bleeding complications for certain high-risk groups, they said, physicians will need to weight this decision for patients individually.
"However, before chemoprevention can be practical, more work is needed to characterize those for whom the potential benefits of aspirin outweigh the hazards," the editorialist Dr. Chan wrote.