ESTRAMUSTINE PHOSPHATE SODIUM - A REVIEW OF ITS PHARMACODYNAMIC AND PHARMACOKINETIC PROPERTIES, AND THERAPEUTIC EFFICACY IN PROSTATE-CANCER

Estramustine phosphate sodium (estramustine phosphate), a unique antitumour agent, is selectively taken. up by prostate cells and exerts antineoplastic effects by interfering with microtubule dynamics and by reducing plasma levels of testosterone. In noncomparative studies of estramustine phosphate in patients with hormone-refractory disease, objective response rates ranging from 19 to 69% have been reported. Preliminary clinical investigations indicate that combining estramustine phosphate with vinblastine, etoposide or paclitaxel improves objective response rates over single-agent treatment although no survival benefit over single-agent treatment has been demonstrated to date. In comparative studies, estramustine phosphate produces similar objective response rates to conventional antineoplastic agents in patients with hopmone-refractory prostate cancer. In previously untreated patients with advanced metastatic hormone-responsive prostate cancel; objective responses are achieved in approximately 80% of patients. Estramustine phosphate appears to be at least as effective as estrogen or flutamide therapy in these patients. Nausea and vomiting are the most frequently observed adverse effects of treatment with estramustine phosphate. While these symptoms are usually mild to moderate in nature, they may occasionally be more troublesome to the patient and necessitate withdrawal of treatment. Cardiovascular complications are a more serious, though less frequently encountered, adverse effect of the drug. However; these complications may be avoided by careful patient selection and prophylactic treatment measures. Unlike some other antineoplastic agents, estramustine phosphate is rarely associated with myelosuppression. In addition to producing similar objective response rates to other established agents, estramustine phosphate improves the subjective status of many patients and has been shown to reduce the intensity of pain and improve the performance status of patients. Thus, estramustine phosphate is a valuable single-agent treatment for patients with hormone-refractory or untreated advanced prostate cancer and, pending results of future phase III trials, may also play an important role as part of a combination regimen (with other agents such as paclitaxel, vinblastine and etoposide) in the treatment of patients with hormone-refractory prostate cancer.