Thromboembolic events with estramustine phosphate-based chemotherapy in patients with hormone-refractory prostate carcinoma: results of a meta-analysis.

Background: Combinations of cytotoxic chemotherapy with estramustine phosphate (EMP), a nornitrogen mustard-estrogen conjugate, are used to treat patients with hormone-refractory prostate carcinoma (HRPC). However, thromboembolic events (TE), including deep venous thrombosis (DVT), pulmonary embolism, stroke, myocardial infarction, and arterial thrombosis, are significant toxicities of these regimens. The current study sought to establish the rate of TE and to determine risk factors for TE.

Methods: A MEDLINE-based search identified EMP-based clinical trials published in the English-language peer-reviewed literature after 1990 in which > or = 20 patients with HRPC were enrolled and TE were clearly documented. Patient characteristics and the dose of EMP given were analyzed to determine their association with the rate of TE.

Results: Twenty-three studies, enrolling a total of 896 patients, were included in the analysis. The overall risk of TE was 0.07 (95% confidence interval [95% CI], 0.05-0.11). The risk of DVT was 0.06 (95% CI, 0.04-0.09). The risks of all other types of TE were <0.01. Using univariate logistic regression analysis, the dose of EMP administered, baseline patient age, and baseline prostate-specific antigen level were not found to be associated with the total risk of TE. The rates of total TE and DVT may be inflated because one of the analyzed studies initially had a very high rate of DVT (25%) when compared with the others.

Conclusions: The rate of TE in men with HRPC who are treated with EMP-based regimens is significant, but it does not appear to be related to the dose of EMP. Whether TE can be prevented with anticoagulant prophylaxis remains to be determined.