Estramustine Potentiates Taxane Effects in Hormone-Resistant Prostate Cancers

NEW YORK, New York—Estramustine (Emcyt) can potentiate the effects of taxanes, and the combination might offer a new therapeutic possibility for patients with hormone-resistant prostate cancer. The combination is being tested in clinical trials described by Anne Hamilton, MD, of New York University Medical Center, at a clinical investigators’ workshop sponsored by the University of Texas M. D. Anderson Cancer Center and Pharmacia Oncology.

“Estramustine is estradiol linked to nor-nitrogen mustard,” Dr. Hamilton explained. “It was originally developed to allow selective delivery of alkylating agents into estrogen-receptor-positive cells. Although it has minimal alkylating activity, the agent depolymerizes cytoplasmic microtubules and binds to tubulin and to microtubule-associated proteins. It inhibits P-glycoprotein and disrupts the nuclear matrix,” she added.

Decrease in PSA Levels

Although trials using single agent oral estramustine in hormone-refractory prostate cancer produced prostate-specific antigen (PSA) response (ie, PSA decrease > 50%) in 37% of patients, the combination of estramustine with paclitaxel (Taxol) produces PSA responses of 50% to 70%, and responses in measurable lesions of 12% to 27%. A combination of estramustine and docetaxel (Taxotere) similarly produces PSA responses in over half the patients. Dr. Hamilton declared that these regimens are now the “standard of care” in hormone-refractory prostate cancer in the United States.

“In hormone-resistant prostate cancer, the combination of antitubulin chemotherapy such as taxanes or vinorelbine (Navelbine) and estramustine offers clinically significant activity. These are frontline therapy options and are now the subject of phase III studies,” Dr. Hamilton said.

Combinations of estramustine and taxanes also have moderate activity in taxane-resistant breast cancer, Dr. Hamilton added.