Docetaxel (Taxotere) combined with estramustine
phosphate (Emcyt) and low-dose hydrocortisone appears to be a
promising treatment for men with hormone-refractory prostate cancer,
according to the results of a phase II trial conducted by the Cancer
and Leukemia Group B (CALGB) and presented at the 1999 meeting of the
American Society of Clinical Oncology (ASCO). The study, funded by
the National Cancer Institute (NCI), found that the combination
treatment was effective and well tolerated.
When hormone therapy is no longer successful in men with
prostate cancer, chemotherapy may be tried, said Diane
Savarese, md, of the University of Massachusetts. However,
current drug therapy, particularly single-agent therapy, confers
limited benefit, and the development of new agents and combinations
of agents may ultimately prove to be the most effective treatment
once hormone resistance has emerged. Indeed, our data suggest that
the docetaxel/estramustine combination may represent an encouraging approach.
The study enrolled 47 men with an Eastern Cooperative Oncology Group
(ECOG) performance status of 0 to 2 whose prostate cancer had
progressed after initial hormone therapy. Patients who had undergone
prior chemotherapy or who had a history of thrombotic events or
severe cardiovascular disease were ineligible for the study.
Participants received intravenous docetaxel, 70 mg/m² on the
second day of every 3-week cycle; oral estramustine, 10 mg/kg/d in
divided doses for 5 days; and oral hydrocortisone, 40 mg/d.
Overall, 40 patients were evaluable for response and/or toxicity. Of
the 39 men with initially elevated prostate-specific antigen (PSA )
levels, 27 (69%) had a greater than 50% decline in PSA. Of these
patients, 21 had a greater than 75% decrease.
Measurable soft-tissue disease was present in 21 of 40 patients who
received at least two cycles of therapy. Of these patients, one had a
complete response after six cycles, and three had a partial response
in soft tissue.
Side effects of the combnation treatment included modest hematologic
toxicity. Gastrointestinal disturbances and nonhematologic toxicity
Based on the favorable results of this study, phase III trials should
be undertaken to compare the combination regimen with other drugs
that have shown activity in patients with hormone-refractory prostate
cancer. including mitoxantrone (Novantrone) and hydrocortisone, said