RATIONALE: Drugs used in chemotherapy and hormone therapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving drugs in different ways may kill more tumor cells. It is not yet known whether estramustine plus docetaxel is more effective than mitoxantrone plus prednisone for prostate cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of estramustine plus docetaxel with that of mitoxantrone plus prednisone in treating patients who have stage IV prostate cancer that has not responded to hormone therapy.

Condition	Treatment or Intervention	Phase
adenocarcinoma of the prostate stage IV prostate cancer recurrent prostate cancer	Drug: docetaxel  Drug: estramustine  Drug: mitoxantrone  Drug: prednisone  Procedure: chemotherapy  Procedure: endocrine therapy  Procedure: hormone therapy  Procedure: steroid therapy	Phase III

OBJECTIVES:

• Compare the overall survival and progression-free survival in patients with hormone-refractory, metastatic adenocarcinoma of the prostate treated with docetaxel and estramustine vs mitoxantrone and prednisone.
• Compare the qualitative and quantitative toxic effects of these regimens in this patient population.
• Compare the quality of life, including palliation of metastatic bone pain and global quality of life, of patients treated with these regimens.
• Record prostate-specific antigen values for future correlations with response and survival in patients treated with these regimens.
• Compare the responses in patients with bidimensionally measurable disease treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to disease status (measurable or evaluable disease progression vs rising PSA only), NCI Common Toxicity Criteria version 2.X pain scale (grade 2 or greater vs less than 2), and SWOG performance status (0-1 vs 2-3). Patients are randomized to one of two treatment arms.

• Arm I: Patients receive oral estramustine 3 times daily on days 1-5 and docetaxel IV over 1 hour on day 2.
• Arm II: Patients receive mitoxantrone IV over 30 minutes on day 1 and oral prednisone twice daily on days 1-21. Treatment in both arms repeats every 3 weeks for a maximum of 12 courses in the absence of unacceptable toxicity or disease progression.

Quality of life is assessed at baseline, after courses 4 and 8, and then at 1 year after randomization.

Patients are followed every 6 months for 2 years and then annually for 1 year.

PROJECTED ACCRUAL: A total of 620 patients (310 per arm) will be accrued for this study within 3.5 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic adenocarcinoma of the prostate
• Unresponsive or refractory to hormonal therapy, as defined by at least 1 of the following criteria:
• Progression of bidimensionally measurable disease
• Progression of evaluable but not measurable disease (bone scan)
• At least 2 consecutive rises in PSA and a PSA level of at least 5 ng/mL
• No minimum PSA required for measurable disease or non-PSA evaluable disease
• Soft tissue disease that has been irradiated within the past 2 months is not considered measurable disease
• Prior orchiectomy OR
• Medical castration using leuprolide or goserelin
• LHRH agonist therapy must continue during study
• Prior nonsteroidal antiandrogens (flutamide, ketoconazole, bicalutamide, or nilutamide) allowed if disease progression occurred
• No third-space fluid accumulation such as ascites or symptomatic pleural effusion
• No brain metastases

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• SWOG 0-3
• Performance status 3 must be due to pain secondary to bone metastases

Life expectancy:

• Not specified

Hematopoietic:

• No hypercoagulability

Hepatic:

• Not specified

Renal:

• Creatinine no greater than 2.0 mg/dL

Cardiovascular:

• No history of myocardial infarction
• No history of congestive heart failure unless well controlled
• No history of cerebrovascular accident or atrial fibrillation
• No active thrombophlebitis
• LVEF at least 50% by MUGA scan or 2-D echocardiogram

Pulmonary:

• No history of pulmonary embolus

Other:

• Recovered from major infections
• No other significant active medical illness
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or stage I or II cancer currently in complete remission

PRIOR CONCURRENT THERAPY: Biologic therapy:

• At least 4 weeks since prior biologic therapy and recovered
• No more than 1 prior biologic therapy regimen
• No concurrent biological response modifiers

Chemotherapy:

• At least 4 weeks since prior chemotherapy and recovered
• No more than 1 prior chemotherapy regimen
• No prior estramustine, taxanes, anthracyclines, or mitoxantrone
• No other concurrent chemotherapy

Endocrine therapy:

• See Disease Characteristics
• At least 4 weeks since prior flutamide or ketoconazole (6 weeks for bicalutamide or nilutamide)
• No concurrent corticosteroids or hormonal therapy (except megestrol for hot flashes or continuing LHRH treatment)

Radiotherapy:

• See Disease Characteristics
• Prior samarium Sm 153 lexidronam pentasodium allowed
• At least 4 weeks since prior radiotherapy and recovered
• No prior radiotherapy to 30% or more of bone marrow
• No prior strontium chloride Sr 89
• No concurrent radiotherapy

Surgery:

• See Disease Characteristics
• At least 3 weeks since prior surgery and recovered

Other:

• At least 4 weeks since prior bisphosphonates
• No prior anticoagulation therapy (i.e., warfarin), except aspirin
• No concurrent bisphosphonates

Arizona
      CCOP - Scottsdale Oncology Program, Scottsdale,  Arizona,  85259-5404,  United States
Florida
      Mayo Clinic, Jacksonville,  Florida,  32224,  United States
Illinois
      CCOP - Carle Cancer Center, Urbana,  Illinois,  61801,  United States
      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61602,  United States
Iowa
      CCOP - Cedar Rapids Oncology Project, Cedar Rapids,  Iowa,  52403-1206,  United States
      CCOP - Iowa Oncology Research Association, Des Moines,  Iowa,  50309-1016,  United States
      Siouxland Hematology-Oncology, Sioux City,  Iowa,  51101-1733,  United States
Minnesota
      CentraCare Health Plaza, Saint Cloud,  Minnesota,  56303,  United States
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States
Nebraska
      CCOP - Missouri Valley Cancer Consortium, Omaha,  Nebraska,  68106,  United States
North Dakota
      Altru Health System, Grand Forks,  North Dakota,  58201,  United States
      CCOP - Merit Care Hospital, Fargo,  North Dakota,  58122,  United States
      Medcenter One Health System, Bismarck,  North Dakota,  58501,  United States
Pennsylvania
      CCOP - Geisinger Clinic and Medical Center, Danville,  Pennsylvania,  17822-2001,  United States
South Dakota
      CCOP - Sioux Community Cancer Consortium, Sioux Falls,  South Dakota,  57104,  United States
      Rapid City Regional Hospital, Rapid City,  South Dakota,  57709,  United States

Study chairs or principal investigators

Daniel P. Petrylak, MD,  Study Chair,  Columbia Presbyterian Medical Center   
Eric J. Small, MD,  Study Chair,  University of California, San Francisco   
Patrick A. Burch, MD,  Study Chair,  Mayo Clinic Cancer Center   

Study ID Numbers:  CDR0000067211; SWOG-S9916; CLB-99808; NCCTG-S9916; CTSU
Record last reviewed:  September 2003
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00004001
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-16