The Southwest Oncology Group (SWOG) announced the beginning of the first major phase III clinical trial comparing the combination of docetaxel(Drug information on docetaxel) (Taxotere) and estramustine(Drug information on estramustine) (Emcyt) to the commonly used combination of mitoxantrone(Drug information on mitoxantrone) (Novantrone) and prednisone(Drug information on prednisone) in the treatment of advanced, hormone-refractory prostate cancer. Patient enrollment is currently underway, with approximately 660 men being recruited. This trial is being conducted by SWOG and is funded by the National Cancer Institute (NCI) in collaboration with the Cancer and Leukemia Group B (CALGB) and North Central Cancer Treatment Group (NCCTG).
Phase I/II studies have shown that the combination of docetaxel and estramustine is very active and well tolerated in patients with hormone-refractory prostate cancer. The encouraging response rates seen thus far with the combination of docetaxel and estramustine provide hope that using a tolerable, more effective combination may prolong life in this group of difficult-to-treat patients, said SWOG study chair Daniel P. Petrylak, md, assistant professor of medicine at Columbia College of
Physicians and Surgeons, and director of the Genitourinary Oncology Program at Columbia Presbyterian Center of New York.
The primary objectives of the study are to: (1) determine whether the docetaxel-estramustine combination improves overall and progression-free survival, as compared with the mitoxantrone-prednisone; and (2) compare toxicities related to the two treatments. Other objectives include assessments of the decline of prostate-specific antigen (PSA) levels and of quality of life among both treatment groups.
Although prior clinical trials using single-agent chemotherapy have yielded objective response rates of 10% to 20% with subjective or stable response rates in another 20% to 40% of patients, no single agent or combination treatment has demonstrated a survival benefit in patients with advanced, hormone-refractory prostate cancer in phase III trials. The reported survival duration in these trials ranges from 5 to 11 months.
Palliative benefit can be achieved by administering mitoxantrone with corticosteroids; however, there is no evidence that survival is prolonged with this therapy. There is an obvious need for new therapies based on novel methods of inhibiting cancer growth, said Dr. Petrylak.
For the present phase III study, participants will be randomized to one of two treatment regimens: (1) oral estramustine taken three times daily for 5 days combined with intravenous docetaxel administered on the second day of treatment; or (2) intravenous mitoxantrone administered every 3 weeks with twice-daily oral prednisone taken for 3 consecutive weeks. A maximum of 12 cycles of either treatment regimen will be administered.
For more information about this study (S9916), contact the National Cancer Institutes toll-free Cancer Information Service (CIS) at 1-800-4-CANCER.