Taking aspirin, and possibly other anticoagulants like warfarin, might reduce the risk of prostate cancer deaths by 50% or more, according to a study involving more than 5,000 men with localized high-risk adenocarcinoma, reported at the ASTRO Annual Meeting.
The researchers caution, though, the usual, that additional research is needed to confirm the findings and to better understand the biological mechanism(s) responsible.
Gastrointestinal bleeding is a well-known risk for individuals taking higher doses of aspirin on a regular basis, but the new findings involved lower doses.
“It is well known that anticoagulants like aspirin and warfarin may interfere with cancer growth and spread,” the study's lead author, Kevin Choe, MD, PhD, a radiation oncologist at the University of Texas Southwestern Medical School in Dallas, noted in a news briefing. “Persons with blood clots are more likely to have cancer, and these anticoagulants prevent metastasis.”
“Studies have been conflicting, but might explain why previous clinical trials with anticoagulation medications have produced mixed results, since most patients in these trials already had metastasis. If the cancer has already metastasized, then anticoagulants may not be as beneficial.”
Dr. Choe and his colleagues used the Cancer of the Prostate Strategic Urological Research Endeavor (CaPSURE) database to investigate whether or not anticoagulants, including aspirin, warfarin, clopidogrel, and/or enoxaparin, had any effect on prostate cancer mortality in men whose cancer had not metastasized.
Data were collected on 5,275 men with localized prostate cancer, 3,523 of whom had undergone radical prostatectomy and 1,772 who were treated with radiation therapy.
Deaths from cancer fell from 10% to 4% in the anticoagulant group during 10-year follow up, a decline largely among patients taking aspirin, and the risk of developing bone metastasis was also lower. The reduction in mortality was greatest in men with high-risk prostate cancer—2% vs 8% at seven years, and 4% vs 22% after 10 years.
Of the men, 1,982 were taking anticoagulants, including warfarin (428 men), clopidogrel (287), enoxaparin (26), and 1,649 receiving aspirin. An additional 408 were taking some combination of the drugs.
The median age was 65, and the median PSA score was 6.0 ng/mL. The proportion of patients with low-, intermediate-, and high-risk disease was 41%, 37%, and 21%, respectively, and 28% of the radiation subjects also received androgen-deprivation therapy (ADT).
Dr. Choe cautioned, however, that it is too soon to recommend aspirin as a standard adjunct to current treatment options in patients with localized high-risk cancer.
Graham Colditz: ‘Exciting’ News
Graham A. Colditz, MD, PhD, the Niess-Gain Professor of Surgery and Associate Director of Prevention and Control at the Siteman Cancer Center of Washington University School of Medicine in Saint Louis, agreed, saying that while the new data are encouraging, it would be premature to start recommending its use in all prostate cancer patients.
“This is a large study and it appears to have been very well done, but the remaining question is whether or not this will hold up in a properly randomized trial,” he said in a telephone interview.
“It's pretty exciting when you see something of this magnitude. The differences over 10 years are significant. Compared to warfarin and other anticoagulants, aspirin appears to be the safest, easiest, and least expensive way to provide some benefit to patients.”
He noted that a recent paper on aspirin use in 1,000 stroke patients found only 22 instances where GI bleeding required emergency treatment—“That's pretty small,” he commented.
However, the big question is exactly how aspirin protects cancer patients. “The major studies have had contradictory results. There might even be a genetic component, but we just don't know,” Dr. Colditz said.
In a paper published in 2007 in the New England Journal of Medicine, researchers at Massachusetts General Hospital, the Dana-Farber Cancer Institute, and Brigham and Women's Hospital reported that aspirin's ability to inhibit the COX-2 enzyme, the action that also underlies aspirin's usefulness for treating pain and inflammation, might also help explain why it works in some cancer patients.
In that study, the investigators found that only aspirin reduced the incidence of colorectal tumors that overexpress COX-2.
The bleeding risks of high-dose aspirin are well documented, which is one reason it is not recommended for colon cancer, he said.
“No drug is entirely free from side effects, and we know the frequency of aspirin's side effects, so I think prostate cancer patients should at least be aware of the data and discuss the option with their oncologist.”
Low-dose aspirin may also impart similar benefits in patients with colon cancer, according to a 20-year study reported in The Lancet as an early online publication.
Researchers led by Peter Rothwell, MD, Professor of Clinical Neurology at Oxford University, studied data from four trials in the UK and Sweden conducted in the 1980s or early 1990s. The studies examined the overall cardiovascular benefits of low-dose aspirin, but data were also collected from centralized data banks to see what the effect were on mortality and diagnoses of colorectal cancer. Among 14,033 patients whose health could be determined for roughly 18 years, 391 had colorectal cancer.
Taking aspirin appeared to reduce the risk by 24% and the risk of death by 35%, and the findings were consistent across all of the four trials.
No increase in benefits was observed beyond a dose of 75 mg, and taking aspirin for five years reduced risk more than a shorter time did.