Nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the risk of developing colorectal cancer by a degree similar to aspirin, although both types of drugs must be taken consistently for a number of years to have a benefit, according to new findings.
In an analysis of more than 10,000 colorectal cancer patients taking low-dose aspirin (75, 100, or 150 mg) continuously for 5 years, the risk for colorectal cancer was reduced by 27%, compared with a matched control group.
In addition, the study, published online August 24 in the Annals of Internal Medicine, indicated that the long-term, consistent use of nonaspirin NSAIDs also reduced the risk for colorectal cancer, particularly for drugs that are selective for cyclooxygenase (COX)-2.
Although there is evidence of a benefit from nonaspirin NSAIDs, there have been no cancer-prevention trials of those drugs in humans, and it was not clear whether the effect would be comparable to that seen with aspirin, said study author John A. Baron, MD, a research professor at the University of North Carolina School of Medicine in Chapel Hill.
Although this study did indeed show that nonaspirin NSAIDs appear to protect against colorectal cancer to a degree similar to aspirin, "it's a sort of good news/bad news thing," Dr Baron told Medscape Medical News.
They protect against cancer, but you have to take the drugs for a long period of time before the cancer-preventive effects become manifest," he explained. "During that period, we show that you need to take aspirin or nonaspirin NSAIDs consistently."
"If you stop and start, and there are months you don't take the medications, the preventive effect dissipates," he noted.
"The fact that this sort of induction period is required means that it takes some time for the aspirin to affect the carcinogenic process and then, in another delay, that the stopping of that process takes a while to show up," Dr Baron continued.
"If you could imagine that you damn the Danube in Serbia, Vienna doesn't see any difference for, I don't know, a week. It takes that long for the change to flow up the river; that is similar for carcinogenesis," he added.
Although the findings confirm the protective effects of aspirin and nonaspirin NSAIDs against colorectal cancer, Dr Baron cautioned against their widespread use.
"The idea that the public should take these medications in the hopes of preventing cancer is appealing, but when you have to take something for, say, 10 years without any benefit, that's a long time for side effects to accumulate," he pointed out.
Previous studies have indicated that aspirin "may not be any better than colonoscopy" in preventing colorectal cancer, he noted. "Now, the fact that aspirin prevents a range of cancers means that you shouldn't just worry about colonoscopy as competing strategy."
"You have to worry about other stuff, and that would add to the appeal of aspirin, but the analyses that have been done so far have only touched upon that," he explained.
Aspirin is also widely used to prevent cardiovascular disease. "The problem is that aspirin, in fact, does prevent heart attack and stroke, but it doesn't really do much for cardiovascular mortality," Dr Baron said. "The studies that have looked at that have found that, despite aspirin's reputation as a cardioprotective drug, the mortality benefit is largely due to cancer."
The nonaspirin NSAIDs, with the exception of naproxen, "may and probably do increase heart attack risk," Dr Baron added. "I would particularly shy away from use of the nonaspirin NSAIDs without consulting the physician."
To examine the association between colorectal cancer risk and the use of low-dose aspirin or other NSAIDs, the researchers conducted a population-based, case–control study of patients diagnosed with first-time colorectal cancer in northern Denmark from 1994 to 2011.
Risk set sampling was used to select participants, and prescription and patient registries were used to gather data on drug use, comorbid conditions, and history of colonoscopy.
The team identified 10,280 colorectal cancer patients and 102,800 control subjects with no history of cancer, inflammatory bowel disease, or familial adenomatous polyposis. The proportion of case and control subjects was similar for ever users of aspirin (22.3% vs 22.4%) and for ever users of nonaspirin NSAIDs (45.1% vs 46.7%).
There was no association between ever use of low-dose aspirin and colorectal cancer risk. However, continuous use of low-dose aspirin — defined as overlapping treatment periods from the start of treatment until 1 year before the index date — for 5 years or more was associated with a reduction in colorectal cancer risk (odds ratio [OR], 0.73).
Ever use of nonaspirin NSAIDs was associated with a marginal reduction in the risk for colorectal cancer (OR, 0.94). Nonaspirin NSAID use for 5 years or more, at an average of 0.3 defined daily doses (DDDs), was associated with an odds ratio of colorectal cancer of 0.70, whereas the odds ratio for consistent use (2 or more prescriptions per year) for at least 5 years was 0.64.
Looking at types of nonaspirin NSAIDs, the team found that the lowest risk for colorectal cancer was seen with NSAIDs with the highest COX-2 selectivity; long-term, high-intensity (average DDD, ≥0.3) COX-2 selective NSAID use was associated with an odds ratio for colorectal cancer of 0.57, compared with 0.73 for COX-2 nonselective NSAIDs (P = .057).
"Our results indicate that if aspirin is taken at doses of 75 to 150 mg, long-term, continuous use is necessary to achieve a substantial protective effect against colorectal cancer," the researchers report.
"The potential use of aspirin and nonaspirin NSAIDs for the prevention of colorectal cancer is limited by the risk for gastrointestinal bleeding and, for most nonaspirin NSAIDs, cardiovascular risks," they add.
"These potential harms will need to be balanced against the chemopreventive benefits that our results indicate," they conclude.
This study was described as "rigorous" by Jack Cuzick, PhD, director of the Wolfson Institute of Preventive Medicine and head of the Centre for Cancer Prevention at Queen Mary University of London, United Kingdom.
The findings reinforce those of a recent review Dr Cuzick and his colleagues conducted on the impact of prophylactic aspirin use on cancer incidence and mortality (Ann Oncol. 2015;26:47-57), as reported by Medscape Medical News. The study results also underline the importance of long-term NSAID use. "That's the big issue here — that it takes about 5 years to really register an effect with aspirin," Dr Cuzick said.
However, he pointed out, the current study does not look at body mass index or the impact of excess weight and obesity on cancer risk, unlike many previous studies.
This includes a recent study on Lynch syndrome patients showing that aspirin reduces the increased risk for colorectal cancer in obese individuals, as reported by Medscape Medical News.
"There's no discussion here about whether weight is relevant or not," Dr Cuzick concluded.
This study was supported the Danish Cancer Society and the Aarhus University Research Foundation. Dr Baron reports an issued use patent for colorectal chemopreventive use of aspirin, which is currently unlicensed. Dr Cuzick is on the advisory board for Bayer.
Ann Intern Med. Published online August 24, 2015. Abstract
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Cite this: Nonaspirin NSAIDs Match Aspirin on Cancer Protection - Medscape - Aug 24, 2015.