Aspirin is often touted as the wonder drug of the 20th century. Famous for its versatility—easing aches and pains, reducing fever and inflammation, preventing heart attacks and stroke—experts have long suspected that aspirin may also play an important role in cancer. Two landmark studies have recently come to some promising conclusions on this count.
The studies, published recently in The New England Journal of Medicine, have shown that aspirin can reduce the development of colorectal polyps in people at high risk for colorectal cancer. Daily aspirin, taken for up to three years, reduced the development of polyps by 19 percent in the participating test subjects.
Though most colorectal polyps never become cancerous, most colorectal cancers trace back to a history of these benign growths found in the lining of the colon or rectum. The new studies suggest that daily aspirin may be an effective preventive measure for people who have had polyps in the past, or who have strong family histories of colorectal cancer.
Below, Dr. Ernest Hawk, chief of gastrointestinal cancer prevention at the National Cancer Institute, talks about the studies and their significance for the future of cancer prevention.
Have we been aware of the preventive benefits of aspirin for some time?
Yes. The story about aspirin's potential to prevent colon cancer has been emerging over the last 30 years. It started with some laboratory observations in animals that suggested that aspirin and aspirin-like drugs could inhibit the development of cancer in the colon of animals. Also, the story of aspirin and colon cancer derives from a large body of observational evidence—looking at populations who use aspirin for other medical conditions versus people who don't and seeing that those using it had lower rates of colon cancer. And this story actually extends beyond the colon, but the story's most consistent in colon and rectal cancer.
How does aspirin work to inhibit the development of colon cancer?
Aspirin inhibits a key family of enzymes called cyclooxygenases, or COX, which are responsible for the synthesis of important mediators of cell proliferation and/or inflammation. In cancer, cells proliferate indefinitely and do not undergo natural cell death. Aspirin and aspirin-like drugs are thought to block cell proliferation by inhibiting the abnormal signaling, and/or to stimulate those cells to die earlier than they would otherwise.
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There are at least two forms of that enzyme, COX-1 and COX-2. COX-2 is believed to be the culprit in inflammation, which is why aspirin and aspirin-like drugs, like ibuprofen, have become popular anti-inflammatory medications. COX-2 also plays a role in cancer development.
Are there any potential adverse effects of aspirin?
Aspirin is a drug, and all drugs have the potential to cause side effects. Aspirin use can be associated most prominently with stomach ulceration or bleeding from the intestinal tract. That occurs in up to 1% of patients who use it, which doesn't seem all that common, but when you're talking about using it in a preventive context, that's quite a frequent occurrence, and that's why aspirin use isn't recommended for the population generally.
Are there other aspirin-like drugs that may work a effectively as aspirin in preventing colon cancer but without the potential side effects?
Aspirin blocks both the COX-1 and COX-2. We've been working for a number of years to try to find a compound that would be just as effective as aspirin but safer. One approach to that is to target the COX-2 enzyme specifically, and so a number of pharmaceutical companies have developed COX-2-selective inhibitors that are publicized broadly in the press,such as celecoxib, or Celebrex. Those drugs have less potential to cause stomach ulceration, about a 50% reduction in the best trials to date, and seem at this point, at least in animals, to be as effective as aspirin in terms of their anticancer effects. But there are no human data right now comparable to these trials to suggest that they should be used in the same way.
There is a small study that was done in a group of particular patients at very high risk for colon cancer, and that study showed significant polyp reduction after six months of celecoxib, but that's the only data that we have right now on an experimental basis to suggest preventive benefits.
So it was approved by the FDA in 2000 as an adjunct to the care of that very high-risk group. It's only for a small segment of the population, but it suggests the preventive benefits that we hope will extend to those at more moderate risk in the future, and those trials are ongoing.
Do you imagine that aspirin or aspirin-like drugs could play a preventive role in other types of cancer in future?
That possibility is certainly there. In animal models, as well as some of the epidemiologic studies looking at populations, it seems as though aspirin and drugs like aspirin decrease the risk not of just colon cancer but of several other cancers, as well. There is suggestive evidence for stomach and esophageal cancer, breast and lung cancer. So there's certainly a potential for aspirin or COX-2-selective inhibitors to reduce the development of cancer in a whole variety of organs, but that remains to be demonstrated definitively, and as of today it can't be a recommendation.
Aspirin is already used by large segments of the American population because of its preventive benefits for cardiovascular events, things like strokes and heart attacks. It's not recommended broadly for everyone in the population, but for those who have certain risk factors above about a 2 to 3% over five years, it's already being used in a preventive manner. And the good news from these studies is that those individuals are probably experiencing not only reductions in cardiovascular risk but also reductions in colon cancer risk because of that use.
Could aspirin or aspirin-like drugs actually play a role in cancer treatment one day?
It certainly is being thought about. There was a study in the early 1990s done by a Scandinavian group in which they took patients with very advanced cancer, essentially patients that were at the end of their therapeutic options, and the question was, can we improve their life by giving them indomethacin, an aspirin-like drug, versus placebo? So they were focused on things like quality of life and pain and ability to maintain weight with these very advanced cancer patients, and what they demonstrated was significant reductions in pain, improvements in terms of maintaining their weight, but also, very surprisingly, a doubling of their average survival, which is really a very striking finding. That had only been demonstrated in one study, but it was important enough that several groups now are looking at the potential of aspirin or aspirin-like drugs to complement existing therapeutic strategies for patients with cancer.
How do you recommend that people interpret the results of these two recent studies? What do you recommend they do?
I think one should take them at face value. In these studies, aspirin was shown to be effective in high-risk patients, and it was associated with very few side effects. In only one of the studies was there an increased risk, I believe, of stroke, and in the other one, no difference whatsoever, and the change in stroke risk was very slight in the one study and may have occurred by chance. So in these studies aspirin was shown to be a relatively safe agent and I think it will provide another therapeutic option for patients at high risk of colon cancer.
Using aspirin as a preventive measure should in no way replace screening and surveillance. We would absolutely recommend all such high-risk patients to undergo screening and surveillance with removal of precancerous polyps, just as they always had. But these studies suggest that aspirin may be able to reduce the development of new polyps, which could complement traditional screening and surveillance.
Taking aspirin for this reason isn't a recommendation to be made to everyone, not even everyone with polyps, but perhaps someone with a strong family history, someone with multiple polyps—not just one, but a history of several polyps. Aspirin might be something that would benefit these patients. Certainly patients with early stage cancer would probably be interested in considering it as an adjunct to usual management. But those sorts of decisions always involve risks as well benefits, and it's best to speak with a physician.
What dosages are recommended?
Based on the published data, as well as the observational data, the current dosing would probably be 325 mg/day—or one adult aspirin—certainly for cancer patients. For those with polyps at lower risk, 81 mg/day—or one baby aspirin—might be the right dose.
What is the significance of these studies?
I think these studies are very important for the field of cancer prevention. For the first time we've demonstrated most definitively that aspirin can reduce the burden of cancer in these high-risk patients. We're trying to improve on these results by using agents with fewer side effects, or placing aspirin or aspirin-like drugs in combination with other drugs that slow the development of cancer. In animal models, those sorts of combinations are extremely effective and no more toxic.
These were important first landmark studies in humans, and I think in the years ahead we will build on this information and hopefully extend it further, making it more relevant to larger segments of the population.
