CHICAGO—The use of anticoagulants may improve the biochemical control of cancer in men undergoing radiation treatment for localized prostate cancer, a retrospective study suggests.
“We found that taking an anticoagulant lowers the risk of biochemical relapse by almost half,” said Kevin S. Choe, MD, PhD, Resident Physician in the Department of Radiation and Cellular Oncology at the University of Chicago, speaking here at the American Society for Radiation Oncology Annual Meeting. “The beneficial effect was most prominent in patients with the highest risk for distant metastases.”
The anticoagulants studied were warfarin, clopidogrel, and aspirin.
May Limit Metastasis
Explaining the rationale for the study, Dr. Choe said, “There is mounting evidence in animal and tissue research that anticoagulants influence multiple cancer processes, including tumor growth, angiogenesis, and metastatic pathways.
“We think the most plausible path is by limiting metastases,” he said.
Alan Pollack, MD, PhD, Chair of Radiation Oncology at the University of Miami, agreed, telling OT that research suggests that the drugs may cause molecular changes that make cancer cells more sensitive to radiation. “If you give anticoagulants, you get better blood flow and maybe better oxidation, which is an intermediary step that is responsible for radiation's effectiveness,” he explained.
Anticoagulants Improve Biochemical Control
The study involved 662 patients with prostate cancer who were treated with radiotherapy at the University of Chicago from 1988 to 2005. Of these men, 196 were taking aspirin, 58 were taking warfarin, and 24 were on clopidogrel. The other men were not taking any blood-thinning medication.
PSA testing was used to monitor biochemical relapse.
At four years, the rate of biochemical control was 91% in the group of prostate cancer patients receiving anticoagulants, compared with 78% in the group not taking the drugs.
Multivariate analysis that adjusted for other risk factors for recurrence showed that taking an anticoagulant was associated with a 46%, significant, lower risk of biochemical recurrence.
The drugs benefited men regardless of whether they received traditional external-beam radiation therapy or radioactive seed implants, Dr. Choe said. The study did not include men who received newer forms of radiation therapy, such as proton therapy.
The researchers did not analyze the three drugs separately.
The proportion of patients with low-, intermediate-, and high-risk disease were 38%, 38%, and 25% respectively, according to National Comprehensive Cancer Network criteria.
When the researchers performed subgroup analyses, there was a trend towards an improvement in biochemical control in low- and intermediate-risk men taking anticoagulants, compared with their counterparts not taking the drugs, Dr. Choe said.
However, freedom from biochemical failure was only significantly better in the high-risk men taking anticoagulants, he said. Their rate of biochemical control was 82%, compared with 58% for high-risk men not taking anticoagulants.
Use of anticoagulants was also associated with a reduced risk of developing distant metastasis, Dr. Choe reported: The four-year distant-metastasis rate was 1% in the group taking anticoagulants vs 5% in the group not taking the drugs.
“This adds to the mounting preclinical evidence that anticoagulants may inhibit a tumor's ability to spread,” he said.
“There are multiple randomized controlled trials looking at whether anticoagulants have an antineoplastic effect. Some were positive and some were negative, but almost all involved patients with end-stage disease. Since our hypothesis is that the drugs are affecting metastatic pathways, you wouldn't expect to see an effect in patients who already have metastatic disease.”
More Prospective Data Needed
Dr. Choe cautioned that more prospective data are needed before it is possible to say with confidence that the benefits of anticoagulants outweigh the risk of toxicity.
Anticoagulants have risks of their own, chiefly internal bleeding, he noted. His own previous research showed that warfarin and clopidogrel increase the risk of rectal bleeding in men undergoing radiation treatment (Choe et al: Int J Radiat Oncol Biol Phys May 20, 2009. Epub ahead of print).
“We need more data before recommending that men undergoing radiotherapy consider taking anticoagulants. But those men with localized prostate cancer who already are on anticoagulants for cardiovascular disease may receive additional benefit if they have to undergo radiotherapy,” Dr. Choe said.
Dr. Pollack agreed that much more research is needed: “This is hypothesis-generating work, which is worthy of further study.”