Aspirin Therapy Can Impair Prostate Cancer Treatment

Aspirin Therapy Can Impair Prostate Cancer Treatment


MedPage Today


BOSTON, Dec. 27 -- Regular use of even low-dose aspirin may interfere with androgen suppression therapy for men with prostate cancer.


Men who used baby aspirin were significantly more likely to have abnormal liver function test results (P=0.02) among men in a study of the antiandrogen flutamide (Eulexin), reported Anthony V. D'Amico, M.D., Ph.D., of the Dana-Farber Cancer Institute here, and colleagues.

Abnormal liver function test results led to premature discontinuation of flutamide in 37% of aspirin users but only 16% of non-users, they said in a letter to the editors published in the Dec. 27 issue of the New England Journal of Medicine.

Oncologists, in collaboration with the patient's cardiologist, need to decide whether he should come off aspirin during hormonal therapy or whether the cardiovascular risk is great enough to forego hormonal therapy if liver function drops, Dr. D'Amico said, especially in view of evidence that antiandrogen therapy may increase heart attack risk.

"It's a trade off," he said. "It's going to have to be decided on an individual basis."

The finding may also have implications for oncologists beyond cautioning about drug-drug interactions, said Philip W. Kantoff, M.D., of Dana-Farber, a co-author of the letter.

"From a prostate cancer standpoint," he said, "this finding raises the potential value of more complete androgen blockade being of great importance in treating early prostate cancer."

In previous studies of high-dose aspirin use for rheumatoid arthritis or osteoarthritis, abnormal liver function tests have been reported in 5% of patients. And an animal study suggested that low testosterone levels contribute to slow metabolism of aspirin.

"In men with prostate cancer," they said, this effect "could have clinical importance because the antiandrogen component of hormone therapy is discontinued when liver function tests become abnormal."

So they retrospectively analyzed the impact of low-dose aspirin in a prospective, randomized controlled trial of radiation therapy with or without at least six months of a luteinizing hormone-releasing hormone agonist and flutamide.

The study included 206 patients with clinically localized prostate cancer and a PSA of at least 10 ng/mL, a Gleason score of at least seven, or radiographic evidence of extraprostatic disease.

The primary outcomes, published in the Journal of the American Medical Association in 2004, showed increased five-year survival (88% versus 78%, P=0.04) and decreased prostate cancer-specific mortality (P=0.02) with the addition of androgen suppression therapy.

Among the other findings of the current report at 7.6 years of follow-up, men who completed six months on a luteinizing hormone-releasing hormone agonist but stopped flutamide early were at 3.50 times higher relative risk of death (95% confidence interval: 1.03 to 11.80, P=0.04) than those who completed six months of both.

Radiation therapy alone was associated with 6.10-fold risk (95% CI: 2.30 to 16.20, P<0.001) compared with radiation therapy plus six months of hormone therapy.

Whereas men who used baby aspirin were more likely to have abnormal liver function test results (P=0.02), those on another common drug, atorvastatin (Lipitor) were not (P=0.13).

"Care givers should be aware of drug-drug interactions when treating cancer patients," Dr. Kantoff concluded, "including the interactions of cancer drugs with [other] prescription and non-prescription drugs, that could decrease the ability to deliver the cancer drug or diminish its effectiveness."

For men who would normally take the occasional aspirin for pain, Dr. D'Amico suggested using non-aspirin painkillers instead during hormonal therapy.

"These medicines don't have the same implications that aspirin appears to have in the setting of hormonal therapy," he said.