S9916, Combination Therapy in Treating Patients With Advanced Prostate Cancer That Has Not Responded to Hormone Therapy

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.

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

• Luteinizing hormone-releasing hormone (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
• Left ventricular ejection fraction (LVEF) at least 50% by Multi Gated Acquisition Scan (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