NEW YORK, New YorkEstramustine (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.