Aspirin reduces colorectal cancer rates by around 60% in those with increased hereditary risk, providing clear case for using aspirin for prevention (CAPP2 study)

The first randomised controlled trial (RCT) to assess aspirin's effect on cancer prevention, published by The Lancet, has shown a reduction in colorectal cancer incidence of over 60% in patients at genetically increased risk who use aspirin long-term. The case for chemoprevention using aspirin in these patients is now clear, say the authors, led by Professor Sir John Burn, Newcastle University, UK.

Various observational studies have suggested aspirin can lower the risk of developing cancer, but this new work is the first RCT to have cancer incidence as its primary end point. The study involved 43 centres in 16 countries and followed nearly 1,000 patients, in some cases for over 10 years. All patients were carriers of Lynch Syndrome, a genetic anomaly that predisposes a person to developing colorectal cancer and a range of other solid organ cancers.

At least 1 in 1000 people carry this disorder which accounts for about 1 in 30 cases of bowel cancer. People with Lynch syndrome are about 10 times more likely that the general population to develop cancer, particularly of the bowel and womb, and often at a young age.

Between 1999 and 2005 a total of 861 people began either taking two aspirins (600 mg) every day for at least two years (434 patients) or a placebo (427). The first analysis of the trial data in 2007 showed no difference in colorectal cancer incidence between those who had taken aspirin and those who had not.

However, by 2010, there had been 19 new colorectal cancers among those who had received aspirin, and 34 among those on placebo, meaning those in the aspirin group had an overall 44% reduced incidence of colorectal cancer. A further analysis focused on the patients who took aspirin for at least 2 years (some 60% of the total), and here the effects of aspirin were even more pronounced: a 63% reduced incidence of colorectal cancer was observed with 23 bowel cancers in the placebo group but only 10 in the aspirin group. The effect began to be seen five years after patients starting taking the aspirin.

Looking at all cancers related to Lynch syndrome, including cancer of the endometrium or womb, almost 30% of the patients taking the placebo had developed a cancer compared to around 15% of those taking the aspirin. No data for adverse events were available for after the study finished; however during the intervention, adverse events did not differ between aspirin and placebo groups.

The authors say: "600 mg aspirin per day for a mean of 25 months substantially reduced cancer incidence after 55·7 months in carriers of hereditary colorectal cancer. Further studies are needed to establish the optimum dose and duration of aspirin treatment...The case for prescription of aspirin to this high-risk group is clear."

The authors add that the CAPP3 study, for which they are currently recruiting, will compare the effects of different doses of aspirin in people with Lynch syndrome. They say: "In the meantime, clinicians should consider aspirin prescription for all individuals judged to be at high risk of colorectal cancer, but taking appropriate measures to minimise adverse effects."

They conclude: "Our results, taken in conjunction with recent research, provide a basis for recommendation of aspirin chemoprevention in Lynch syndrome as standard of care."

"What surprised us was that there was no difference in the number of people developing polyps which are thought to be the precursors of cancer. But, many fewer patients who had been taking aspirin years before went on to develop cancers," says Professor Tim Bishop* from the University of Leeds, whose team was responsible for the statistical analysis.

Professor Burn adds: "We have succeeded in showing the benefits of aspirin because we had a lot of long term data and because Lynch syndrome is associated with rapid development of cancer. It has also demonstrated how our research community and families with inherited forms of cancer can work together to answer questions important for the whole population."

"Before anyone begins to take aspirin on a regular basis they should consult their doctor as aspirin is known to bring with it a risk of stomach complaints including ulcers," advises Professor Burn. "However, if there is a strong family history of cancer then people may want to weigh up the cost-benefits particularly as these days drugs which block acid production in the stomach are available over the counter," he concludes.

In a linked Comment, Dr Andrew T Chan, Massachusetts General Hospital, and Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA, and Dr Scott M Lippman, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA, say: "As the first randomised trial of aspirin with colorectal cancer as the primary endpoint, CAPP2 also certainly moves us closer to a more definitive answer on aspirin's overall role in prevention of colorectal cancer.

Unfortunately, prohibitive logistics make a randomised trial of aspirin prevention with a colorectal cancer endpoint in a sporadic-risk population unlikely. Therefore, these results from CAPP2 and previous evidence arguably support more general recommendations to consider aspirin for prevention of colorectal cancer in the context of individualised risk-benefit assessments."

Source: The Lancet