Anticoagulant use predicts survival in metastatic PCa

Orlando, FL-Anticoagulation while on docetaxel (Taxotere) chemotherapy appears to be an independent predictor of survival in men with metastatic castration-resistant prostate cancer (mCRPC).

That unexpected finding came out of a retrospective study presented at the Genitourinary Cancers Symposium in Orlando, FL.

“This finding is surprising and paradoxical, given that the occurrence of venous thromboembolism might be expected to negatively influence overall survival. If validated by further study, these data may provide the impetus to explore the antitumor potential of anticoagulants in prospective clinical trials,” said first author Caroline F. Pratz, MSN, nurse practitioner at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center in Baltimore, who worked on the study with Emmanuel S. Antonarakis, MBBCh, and Robert A. Brodsky, MD.

A retrospective review of medical records of 247 consecutive patients treated with first-line docetaxel for mCRPC between Jan. 1, 1999, and Jan. 1, 2010, showed that patients who received concomitant anticoagulation therapy had a 39% relative reduced risk of mortality compared with men who did not receive anticoagulation during that time period. The review focused only on men who were being treated with docetaxel-containing regimens.

Of the 247 men, 29 were treated with anticoagulation: 17 with low-molecular-weight (LMW) heparin and 12 with warfarin sodium (Coumadin). Indications for anticoagulation therapy included deep vein thrombosis ([DVT] 15 patients), pulmonary embolism ([PE] nine patients), and both DVT and PE in five patients. Use of LMW heparin was associated with a significant 42% reduction in the relative risk of death (p=.048), while the use of warfarin achieved an 18% relative risk reduction in death that was not statistically significant.

A univariate analysis found that any anticoagulant use was associated with improved survival. Median overall survival was 20.9 months for those on an anticoagulant versus 17.1 months for the group not taking anticoagulants. A multivariate analysis found that anticoagulation use was a significant independent predictor of overall survival after adjusting for other prognostic factors.

The mean age was 67.5 years and 75% of patients were Caucasian. Twenty percent had a radical prostatectomy, 34% radiation therapy, 19% both surgery and radiation, and 20% had no prior treatment.

Explanation for findings unknown

The explanation for these findings is not clear. Pratz said that some studies have shown that heparin has anticancer effects, but the present study did not evaluate this.

Commenting on this study, Mark K. Buyyounouski, MD, said that the study added to a growing body of evidence demonstrating that anticoagulation improves outcomes in patients with prostate cancer.

“These results are particularly compelling, given the advanced nature of the disease in the study population,” said Dr. Buyyounouski, associate professor of radiation oncology and director of clinical research at Fox Chase Cancer Center, Philadelphia.

He agreed that further study is needed to determine the ideal method, dose, and timing of anticoagulation as well as the risks versus benefits. At this time, until these results are validated, men with prostate cancer should not be receiving anticoagulation to improve outcomes unless indicated.UT