March 27, 2012

How Much Aspirin Is Too Much of a Good Thing?

March 26, 2012, 6:20 pm

By RONI CARYN RABIN, Reporter

More than 40 million American adults already take an aspirin a day to prevent heart disease. Now many more are weighing the pros and cons of daily aspirin use in light of new studies finding that it also may reduce the risk of many cancers and stop the spread of tumors.

Six months ago Vanessa Brannan, a 31-year-old Seattle mother of two, learned she had colon cancer and Lynch syndrome, an inherited condition that increases risk of the disease and other cancers. Some of the best data on aspirin’s effectiveness against cancer has been found in patients like Mrs. Brannan. In one British study, patients with Lynch syndrome who took aspirin for two years cut their risk of colon cancer in half.

Yet doctors still don’t know how much aspirin these patients — or anyone else — should take. So Mrs. Brannan is taking 325 milligrams daily, though patients in the British study received nearly twice that amount. Her oncologist, though, recommended just an 81-milligram baby aspirin. “We kind of decided to split the difference and get as much aspirin into me as we can, knowing that higher amounts have been proven to work,” she said.

She is not the only cancer patient grappling with uncertainty. The science about daily aspirin and its effect on cancer is still in its infancy. In research studies, subjects have received doses ranging from 75 milligrams a day to 1,200 milligrams a day.

Now some scientists think low doses may work if they’re taken every day; American clinical trials of every-other-day aspirin had no effect on cancer rates at all.

Renewed interest in aspirin was set off by studies by researchers at Oxford, published last week in The Lancet, that found that after just three years of daily aspirin use, the risk of developing cancer was reduced by almost 25 percent when compared with a control group not taking aspirin.

Over six and a half years on average, daily aspirin reduced the risk of metastatic cancer by 36 percent and the risk of adenocarcinomas — common solid cancers including colon and prostate cancer — by 46 percent.

The studies found large reductions in colon and esophageal cancers, and hinted at benefits for the prevention of breast, uterine, ovarian and pancreatic cancers and lung cancer in smokers. The mechanism is believed to be aspirin’s suppression of inflammation, which is believed to play a role in cancer, and its inhibition of COX-2, an enzyme that helps tumors grow.

Critics say the new analyses may not be reliable because they are based on data from studies that were designed to assess aspirin’s effect on vascular disease, not cancer.

“The data with regard to breast cancer is interesting, but it is not actionable — period,” said Dr. Clifford A. Hudis, chief of the breast cancer medicine service at Memorial Sloan-Kettering Cancer CenterinNew York City.

But he does not dismiss aspirin altogether, saying it may help a specific subgroup of people at high risk for breast cancer because of changes related to obesityand inflammation. “That is far different than saying everybody should take it,” he said.

Public health experts worry about widespread use of aspirin, because the drug increases the risk of gastrointestinal bleeding, ulcers and hemorrhagic strokes that can be fatal. An analysis in Archives of Internal Medicine in January found that for every 162 people who took aspirin, the drug prevented one nonfatal heart attack but caused about two serious bleeding episodes.

Aspirin may be a household staple, but it is also a potentially toxic drug, said Dr. Khosrow Kashfi, an associate medical professor at the City College of New York, who is working to develop a safer but more potent form of aspirin. “If you are telling healthy people that they should take a drug for a long period of time, for years — at what dose we don’t even know, but for a long time — then safety becomes of paramount importance,” he said.

It may be necessary to treat as many as 2,000 patients with daily aspirin to prevent a single case of colon cancer a year, said Dr. Alfred Neugut, a professor of cancer research, medicine and epidemiology at Columbia University. “The question is: what does aspirin do on a daily basis to 2,000 people?” If 20 or more of those patients suffer bleeding episodes, then taking aspirin to prevent cancer isn’t worthwhile, he added.

But if research were to uncover significant reductions in other common cancers, “you could start to argue, for general cancer prevention, the cumulative benefit may make it worthwhile.”

Other researchers are more enthusiastic about aspirin’s prospects as a cancer treatment.

“These studies may not be perfect, but do we say, ‘Wait, and we’ll do a 15-year study to answer this’?” said Dr. Scott Kopetz, who treats gastrointestinal cancers at M.D. Anderson Cancer Center in Houston. “Or do we say, ‘This is really good, compelling data, and we need to start taking this into consideration for the individual who may be at cancer risk’?”

So what’s a consumer to do? The best evidence on aspirin’s potential as a cancer preventive has been found in clinical trials of patients at increased risk for colon cancer because of a strong familial or personal history of colon cancer.

“In that case, the benefit of long-term aspirin is likely to outweigh the risks,” said Dr. Peter M. Rothwell, the Oxford professor who led the recent Lancet studies. Dr. Rothwell said research indicates that a low 75-milligram dose of aspirin a day mitigates risk, but he urged patients to seek individualized guidance from a physician.

Those who use blood thinners or have stomach ulcers, blood clot disorders, liver or kidney disease, uncontrolled blood pressure or risks for hemorrhagic stroke should not take aspirin, said Dr. Asad Umar, chief of the gastrointestinal cancers research group in the National Cancer Institute’s Division of Cancer Prevention.

If you already take aspirin, don’t stop suddenly without telling your physician. Don’t take it on an empty stomach, and avoid alcohol and other anti-inflammatory drugs.

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