Docetaxel, Estramustine, and Thalidomide in Treating Patients With Androgen-Independent Metastatic Adenocarcinoma of the Prostate

OBJECTIVES:

Primary

• Determine the prostate-specific antigen response in patients with androgen-independent metastatic adenocarcinoma of the prostate treated with docetaxel, estramustine, and thalidomide.

Secondary

• Determine the survival duration in patients treated with this regimen.
• Determine the pharmacokinetics of both docetaxel and thalidomide in patients treated with this regimen.
• Determine whether any pharmacodynamic relationships exist between plasma concentrations of docetaxel and/or thalidomide and clinical activity or toxicity of this regimen in these patients.
• Determine the existence of and quantification of circulating prostate cancer cells in patients before and after treatment with this regimen.
• Determine genotype, with regard to cytochrome P450 2C19 polymorphism, in patients treated with this regimen.
• Correlate genotype with pharmacokinetics and efficacy of this regimen in these patients.
• Determine the changes in molecular markers of angiogenesis (including, but not limited to, serum and urine vascular endothelial growth factor) in patients before and after treatment with this regimen.
• Determine the toxicity profile of this regimen in these patients.

OUTLINE: This is an open-label study.

Patients receive docetaxel IV over 30 minutes on days 2, 9, and 16, oral thalidomide once daily on days 1-28, and oral estramustine three times daily on days 1-3, 8-10, and 15-17. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 33-60 patients will be accrued for this study within 11-20 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate

• Metastatic disease
• Androgen-independent disease
• Clinically progressive disease documented by at least 1 of the following parameters:

• Two consecutively rising prostate-specific antigen (PSA) levels taken at least 1 week apart

• PSA ≥ 5.0 ng/mL
• Continued rise in PSA 4 weeks after discontinuation of prior flutamide OR 6 weeks after discontinuation of prior bicalutamide or nilutamide (for patients treated with anti-androgen agents)
• At least 1 new lesion on bone scan
• Progressive measurable disease
• Must have undergone bilateral surgical castration OR continue on a gonadotropin-releasing hormone agonist
• No brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count > 1,500/mm^3
• Platelet count ≥ 100,000/mm^3*
• Hemoglobin ≥ 7.5 g/dL* NOTE: *No transfusions within the past 2 weeks

Hepatic

• AST and ALT < 2.5 times upper limit of normal (ULN)
• Bilirubin < ULN (≤ 3.0 times ULN for patients with Gilbert's syndrome)
• Alkaline phosphatase ≤ 2.5 times ULN OR
• Fractionated hepatic alkaline phosphatase ≤ 2.5 times ULN

Renal

• Creatinine ≤ 1.5 mg/dL OR
• Creatinine clearance ≥ 40 mL/min

Cardiovascular

• No transient ischemic attacks or cerebrovascular accident within the past 2 years
• No myocardial infarction within the past 6 months
• No uncontrolled congestive heart failure
• No uncontrolled angina pectoris
• No thromboembolic disease

Other

• No peripheral neuropathy ≥ grade 2
• No cognitive impairment that would preclude study participation or giving informed consent
• No other active malignancy within the past 2 years except non-melanoma skin cancer or superficial bladder carcinoma
• Fertile patients must use effective contraception for at least 1 month before, during, and for at least 1 month after study treatment

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior thalidomide

Chemotherapy

• No prior docetaxel
• No prior estramustine
• No prior chemotherapy for metastatic prostate cancer

Endocrine therapy

• See Disease Characteristics

Radiotherapy

• Recovered from prior radiotherapy

Surgery

• See Disease Characteristics
• Recovered from prior surgery

Other

• No concurrent antiretroviral therapy for HIV-positive patients
• No concurrent complementary or alternative therapy that would interact with study drugs
• No concurrent herbal or nutritional products or dietary supplements that would interact with study drugs
• No concurrent aprepitant as secondary prophylaxis or antiemetic treatment