Trial Information

Phase III Randomized Study Of Adjuvant Hormonal Therapy With And Without Docetaxel And Estramustine In Patients With Advanced Prostate Cancer Or With A High Risk Of Relapse

OBJECTIVES:

- Compare the 8-year survival rate, in terms of clinical and biological remission, of
patients with locally advanced prostate cancer or with a high risk of relapse treated
with neoadjuvant releasing factor agonist therapy and antiandrogen therapy with or
without docetaxel and estramustine given before local radiotherapy or prostatectomy.

- Compare the prostate-specific antigen level at 3 months in patients treated with these
regimens.

- Compare cancer progression by ultrasound in patients treated with these regimens.

- Compare survival without clinical remission of patients treated with these regimens.

- Compare the overall survival of patients treated with these regimens.

- Compare the toxicity of these regimens in these patients.

- Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
Gleason score (7 or under vs over 7), T stage (T1 or T2 vs T3 or T4), prostate-specific
antigen level (20 ng/mL or less vs greater than 20 ng/mL), and lymph node involvement (N0 vs
N1 or N2). Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive oral antiandrogen therapy comprising nilutamide twice daily or
bicalutamide once daily or flutamide 3 times daily or cyproterone 4 times daily.
Patients also receive docetaxel IV over 1 hour on day 2 and estramustine on days 1-5.
Treatment repeats every 21 days for a total of 4 courses. Patients also receive
luteinizing hormone-releasing hormone (LHRH) therapy IV comprising buserelin
subcutaneously (SC) every 2 months or triptorelin, leuprolide, or goserelin SC every 3
months.

- Arm II: Patients receive antiandrogen and LHRH therapy as in arm I. Beginning
approximately 21 days after chemotherapy is completed, patients with N0 disease undergo
radiotherapy 5 days a week for 6-7 weeks or radical prostatectomy. Patients with N1 or
N2 disease undergo radiotherapy or no further local treatment.

Hormonal therapy continues in both arms for 3 years in the absence of disease progression or
unacceptable toxicity.

Quality of life is assessed at baseline, at 3 months, and at 1 year.

Patients are followed every 6 months for 5 years.

PROJECTED ACCRUAL: A total of 250 patients (125 per treatment arm) will be accrued for this
study within 3 years.