Phase II Evaluation of Early Oral Estramustine, Oral Etoposide and Intravenous Paclitaxel in Combination With Hormone Therapy in Patients With High-Risk Metastatic Adenocarinoma of the Prostate

OBJECTIVES:

• Determine the progression-free and overall survival in patients with high-risk metastatic adenocarcinoma of the prostate treated with early estramustine, etoposide, and paclitaxel with combined androgen-blockade therapy.
• Determine the type, frequency, and severity of toxicity of this regimen in this patient population.

OUTLINE: This is a multicenter study.

• Androgen-blockade therapy: Patients receive a standard regimen of luteinizing hormone-releasing hormone agonist therapy comprising either goserelin subcutaneously once monthly or once every 3 months or leuprolide intramuscularly once monthly, once every 3 months, or once every 4 months. Patients also receive a standard regimen of antiandrogen therapy comprising oral bicalutamide, oral flutamide, or oral nilutamide once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.
• Chemotherapy: Beginning 14-30 days after initiation of androgen-blockade therapy, patients receive oral estramustine three times daily and oral etoposide once daily on days 1-14 and paclitaxel IV over 1 hour on day 2. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months until disease progression, every 6 months for 2 years, and then annually for 3 years.