OBJECTIVES:

• Determine the time to objective progression, response rate, and duration of response in patients with hormone-refractory metastatic prostate cancer treated with bevacizumab, estramustine, and docetaxel.
• Determine the toxicity of this regimen in these patients.
• Assess the relationship of baseline vascular endothelial growth factor levels in urine and plasma and changes in these levels with response and duration of response in patients treated with this regimen.

OUTLINE: This is a multicenter study. Patients are stratified according to urine vascular endothelial growth factor level (low vs high).

Patients receive oral estramustine 3 times daily on days 1-5 and docetaxel IV over 1 hour followed by bevacizumab IV over 30-90 minutes on day 2. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed at least every 3 months for 2 years.

PROJECTED ACCRUAL: A total of 72 patients (36 per stratum) will be accrued for this study within 18 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate

• Metastatic disease despite castrate levels of testosterone due to orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonist

  • Refractory to standard androgen deprivation therapy

• Measurable disease with any PSA level

  • Target lesion at least 20 mm by physical exam or chest x-ray OR
  • At least 10 mm by spiral CT scan
  • Histological confirmation of neoplastic nature required if disease is confined to only 1 target lesion OR

• Non-measurable disease with PSA at least 5 ng/mL

  • Bone lesions
  • Pleural or pericardial effusions or ascites
  • CNS lesions or leptomeningeal disease
  • Previously irradiated lesions, unless progression documented after radiotherapy

• Progressive disease

  • Objective evidence of greater than 20% increase in the sum of the longest diameters of target lesions for measurable disease
  • Progression by bone scan or PSA for non-measurable disease
• Castrate levels of testosterone must be maintained
• Serum testosterone no greater than 50 ng/mL for patients without prior bilateral orchiectomy

PATIENT CHARACTERISTICS:

Age:

• Any age

Performance status:

• CTC (ECOG) 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than upper limit of normal (ULN)
• AST no greater than 1.5 times ULN

Renal:

• Creatinine no greater than 1.5 times ULN
• Urinalysis no greater than 1+ protein on dipstick

Cardiovascular:

• No myocardial infarction or significant change in anginal pattern within the past year
• No congestive heart failure (New York Heart Association class II-IV heart disease)
• No deep vein thrombosis within the past year

Pulmonary:

• No pulmonary embolus within the past year

Other:

• No clinically significant peripheral neuropathy
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior antiangiogenesis agents, including thalidomide and bevacizumab

Chemotherapy:

• No prior cytotoxic chemotherapy, including estramustine and suramin
• No other concurrent chemotherapy

Endocrine therapy:

• See Disease Characteristics
• At least 4 weeks since any hormonal therapy, including ketoconazole, aminoglutethimide, corticosteroids, flutamide, or megestrol
• At least 6 weeks since prior bicalutimide and nilutimide
• No concurrent hormonal therapy except steroids for adrenal insufficiency or nondisease-related conditions (e.g., insulin for diabetes)
• Concurrent testicular androgen suppression (e.g., LHRH analog) allowed, if initiated before study

Radiotherapy:

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy and recovered
• At least 8 weeks since prior strontium chloride Sr 89 or samarium Sm 153 lexidronam pentasodium
• No concurrent radiotherapy

Surgery:

• See Disease Characteristics
• At least 4 weeks since prior major surgery and recovered

Other:

• No requirement for full-dose or parenteral anticoagulation
• Daily prophylactic aspirin allowed
• No concurrent bisphosphonate therapy unless initiated at least 1 month prior to study with progressive disease despite this therapy