A Prospective Randomized Phase III Study Comparing Hormonal Therapy +/-Docetaxel

Non-Metastatic High-Risk Prostate Cancer Patients With Biochemical Relapse Only After Local Treatment. A Prospective Randomized Phase III Study Comparing Hormonal Therapy +/-Docetaxel

The primary objective was to evaluate the PSA (biochemical) progression-free survival (PFS) of high-risk metastasis-free PC patients, treated with LH-RH agonist for one year with or without docetaxel after prior radical prostatectomy (RP) or radiotherapy (RT).

The study was powered at 80% to detect a 25% improvement in biochemical PFS for a total sample size estimated at 252 patients, with a two-sided type I error rate of 5% (non-parametric methods.

Docetaxel was shown to be active in metastatic hormone-refractory prostate cancer (PC) in phase III trials (1-2). It is likely to demonstrate a substantial role in the management of early-stage PC patients in the neoadjuvant and adjuvant settings, where clinical trials are underway.•53% of all men who undergo radical prostatectomy will develop prostate-specific antigen (PSA) elevations in the 10 years following surgery, with approximately 77% of these recurrences occurring within the first 2 years.A prospective, multicenter, national, randomized, two-arm, phase III study comparing hormonal treatment (LH-RH agonist alone) with or without docetaxel was designed to evaluate the interest of chemotherapy in non-metastatic prostate cancer patients at high risk of systemic recurrence after initial treatment (radical prostatectomy or radiotherapy).

1. PETRYLAK DP, et al: Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 351:1513-1520, 2004
2. TANNOCK IF, de Wit R, Berry WR, et al: Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 351:1502-1512, 2004

Inclusion Criteria:

• Histologically documented adenocarcinoma of the prostate
• Previous treatment with either radical prostatectomy or radiation therapy
• Salvage radiotherapy for local relapse allowed
• Neoadjuvant or per radiotherapy Hormonal therapy allowed in case of more than 6 months free-interval before first rising PSA
• Life expectancy of more than 12 months
• Non metastatic disease documented by imaging including radionuclide bone scan
• ECOG performance status 0-1
• ANC > 1,500/mm3
• Platelet counts > 100,000/mm3
• SGOT and/or SGPT may be up to 2.5 x ULN

Patients at high risk of biological relapse defined by:

• Gleason > 8
• PSA-DT < 6 months
• Positive surgical margins
• PSA velocity > 0.75 ng/mL/year
• Pathological pelvic lymph nodes involvement (pN+)
• Time from initial treatment until inclusion < 12 months

Exclusion Criteria:

• Prior chemotherapy by taxanes and estramustine phosphate
• Documented local recurrence of prostate cancer or documented metastatic disease
• History of other malignancy within the last 5 years other than curatively treated basal cell carcinoma of the skin
• Active infection
• Significant cardiac disease, angina pectoris or myocardial infarction within twelve months
• Clinically significant neuropathy
• Medical condition requiring the use of concomitant corticosteroids
• Prohibited concomitant therapy with experimental drug.
• Participation in another clinical trial for the period < 30 days