September 22, 2009 (Berlin, Germany) — Using aspirin on a daily basis offers protection against colorectal cancer in individuals with Lynch syndrome, and that protection continues for years even after aspirin is discontinued, according to research presented here at the 15th Congress of the European CanCer Organization and the 34th European Society for Medical Oncology Multidisciplinary Congress.

Aspirin also reduced the risk for endometrial cancer in this population.

The results were particularly exciting, said lead author John Burn, MD, medical director and head of the Institute of Human Genetics, Newcastle University, Newcastle upon Tyne, United Kingdom. "We stopped giving the aspirin after 4 years and yet the effect is continuing. It is directly correlated with the duration of aspirin use in the trial."

Results Seen Over Long Term

The chemopreventive effect of aspirin was not seen immediately. The initial results of the study were published last year (N Engl J Med. 2008;359:2567-2578), and Dr. Burn noted that they were "profoundly disappointing," because there was no difference in neoplasia at an average of 29 months after randomization. The rate of colorectal cancer was similar in those taking aspirin and those taking placebo.

However, the researchers noted that individuals who had participated in early cardiovascular trials with aspirin had fewer cases of colorectal cancer after 10 years. That was an impetus for "us to keep trying," Dr. Burn said.

About 5 years after initial trial randomization, the incidence of new malignancies in the aspirin and placebo groups began to diverge, and the number of cases of colorectal cancer in aspirin users declined. The protective effect of aspirin appeared to persist for at least 6 years after the last episode of aspirin use, and also correlated with the duration of aspirin use during the study, the researchers note.

In the original study, 1071 people with Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer, were randomized to 600 mg of aspirin per day and/or 30 g of Novelose, a resistant starch that escapes digestion in the small intestine.

Dr. Burn pointed out that even though case–control and epidemiologic studies have reported that the use of nonsteroidal anti-inflammatory drugs decreases the risk for colorectal cancer, randomized controlled trials have failed to show this effect.

"We decided to take a different approach and look at Lynch syndrome," he said. "We thought it was an interesting group for a chemoprevention study, since these people are very motivated."

Adenomas Not Prevented, Bleeding Incidents Minimal

Dr. Burn emphasized that, in this study, the goal was not to prevent adenomas but to prevent cancer. About 100 study participants developed adenomas, but there was no propensity to develop cancer. "We didn't prevent the adenomas from occurring, but we prevented adenomas from becoming malignant," he said.

To date, the researchers have observed only 6 cases of colon cancer among the study participants who used aspirin, compared with 16 cases in the placebo group. Six individuals also developed multiple colorectal cancers and, of this group, only 1 was taking aspirin.

Bleeding was also not an issue, despite the high dose of aspirin. In the aspirin group, 11 participants experienced notable gastrointestinal bleeding, as did 9 in the placebo group. Individuals in the aspirin group also had a lower rate of cardiovascular events.

Extrapolating the Data

It is currently unclear how much of these data can be extrapolated to other populations. "About 1 in 6 of all colon cancers has some type of breakdown in this gene system," said Dr. Burn. "So one might say that if it prevents cancer in the inherited form of the disease, it might work well in other forms of the disease."

However, José Baselga, MD, president of ESMO, is not certain that similar results will be experienced in other patient groups. "I'm not sure that other types of colorectal cancer will respond as well," he told Medscape Oncology. "It does seem to be a very long process with a long follow-up time."

The study was funded by the Medical Research Council in the United Kingdom and by Cancer Research UK.

15th Congress of the European CanCer Organization (ECCO 15) and the 34th European Society for Medical Oncology (34th ESMO) Multidisciplinary Congress: Abstract 6000. Presented September 21, 2009.


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