ANTICOAGULANTS FOR PROSTATE CANCER?

November 5, 2009 (Chicago, Illinois) — Anticoagulants are indicated for the treatment of cardiovascular disease but might have a role to play in prostate cancer.

Anticoagulants, including aspirin, warfarin, and clopidogrel, were associated with improved biochemical control of localized prostate cancer in men treated with radiation therapy, according to a new retrospective study of 662 men.

The potential benefit is most pronounced in patients with high-risk localized disease, according to the study's lead author, who presented a poster here at the American Society for Radiation Oncology 51st Annual Meeting.

The current study looked only at men with prostate cancer treated with radiation, not with surgery, explained Kevin S. Choe, MD, PhD, from the University of Chicago Pritzker School of Medicine in Illinois.

The benefit seen in men who undergo radiotherapy while taking anticoagulants likely stems from an "interaction" between the radiation and the drugs, reported Dr. Choe.

At 4 years, biochemical control, or the absence of biochemical relapse as measured by prostate-specific antigen testing, was statistically significantly better in the group of prostate cancer radiotherapy patients receiving anticoagulants than in the group not receiving the blood-thinning therapy (91% vs 78%; P = .0002).

"We need more data before recommending that men undergoing radiotherapy consider taking anticoagulants," said Dr. Choe. However, the young investigator, who is a resident in radiation oncology at the University of Chicago, also put a positive spin on the results. "Those men with localized prostate cancer who already are on anticoagulants for cardiovascular disease may receive additional benefit when they undergo radiotherapy."

An expert in cancer and anticoagulants approached by Medscape Oncology for comment believes that the use of these agents holds considerable promise in oncology. "There is much that can be done that is low cost and effective," said Leo R. Zacharski, MD, from the White River Junction VA Medical Center in Vermont and the Dartmouth School of Medicine in Hanover, New Hampshire.

There is a "very large" literature on the subject, said Dr. Zacharski, citing the "dramatic effects" of anticoagulants on small-cell lung cancer as an example. "It is too bad that few people pay attention to the literature on this," opined Dr. Zacharski.

Dr. Zacharski also had a theory about the current findings. "In my opinion, the most likely explanation for the findings is that people who take anticoagulants tend to have slightly increased blood loss, which reduces the amount of iron in their bodies," he said.

In a randomized trial of iron reduction in men with peripheral arterial disease, Dr. Zacharski and colleagues found a statistically significant reduction in new cancer diagnosis and cancer-specific mortality (J Natl Cancer Inst. 2008;14:996-1002). The effect was seen for prostate cancer as well as other cancers, he said.

he current study was an outgrowth of another study in prostate cancer patients, in which Dr. Choe and colleagues investigated rectal bleeding. Prostate cancer patients treated with radiotherapy while taking anticoagulants had a significantly higher risk for this bleeding than patients not taking anticoagulants, he said.

Given this complication, if anticoagulants were ever to be recommended for use in these men, "it would need to be planned out very carefully," said Dr. Choe.

Subgroup Analysis: Benefit Only Significant in High-Risk Men

The new study looked at men with localized prostate cancer, Dr. Choe noted. This is appropriate, suggested Dr. Zacharski, who said that "established prostate cancer does not respond to anticoagulants."

The study cohort consisted of 662 patients with prostate cancer who were treated with radiotherapy at the University of Chicago from 1988 to 2005. Of these men, 243 were receiving warfarin, clopidogrel, and/or aspirin. Most of the men were receiving aspirin alone (n = 161) or warfarin alone (n = 42).

The men were treated with seed implants and/or external-beam radiation. The type of radiation received did not influence biochemical control outcomes, said Dr. Choe. About half the men also received short-term androgen-deprivation therapy.

Among the 243 patients, risk was low in 38%, intermediate in 38%, and high in 25%, according to National Comprehensive Cancer Network criteria.

In a subgroup analysis, the improvement in biochemical control was apparent among low- and intermediate-risk men taking anticoagulants, compared with the respective risk groups of men not taking the drugs.

However, biochemical control was only statistically significant in the high-risk men (n = 165). In that subgroup, the men taking anticoagulants (n = 52) had a 4-year rate of freedom from biochemical recurrence (i.e., biochemical control) of 82.4%, compared with 57.6% of those not taking anticoagulants (n = 113; P = .0007).

"The benefit of biochemical control appears to be most pronounced in men with localized high-risk disease," said Dr. Choe.

Anticoagulants had another benefit in the study: the drugs were associated with a reduced rate of metastasis.

The distant metastasis rate at 4 years was lower in the group taking anticoagulants than in the group not taking anticoagulants (1% vs 5%; P = .0248). "Anticoagulants may inhibit a tumor's ability to spread," said Dr. Choe, adding that "mounting preclinical evidence" supports this hypothesis.

Dr. Choe and Dr. Zacharski have disclosed no relevant financial relationships.

American Society for Radiation Oncology (ASTRO) 51st Annual Meeting: Abstract 2269. Presented November 2, 2009