Docetaxel With or Without Oblimersen in Treating Patients With Hormone-Refractory Adenocarcinoma (Cancer) of the Prostate

OBJECTIVES:

Primary

• Compare the activity of docetaxel with or without oblimersen, in terms of prostate-specific antigen response, in patients with hormone-refractory adenocarcinoma of the prostate.
• Compare the toxicity of these regimens in these patients.

Secondary

• Compare the time to progression in patients treated with these regimens.
• Compare survival of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, metastatic disease (M0 vs M1 with non-measurable lesions only vs M1 with measurable lesions), prior estramustine (yes vs no), and prior bisphosphonates (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive docetaxel IV over 1 hour on day 5 and oblimersen IV continuously on days 1-7.
• Arm II: Patients receive docetaxel IV over 1 hour on day 1. In both arms, treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 8 weeks until progressive disease and then every 16 weeks thereafter.

PROJECTED ACCRUAL: A total of 102 patients (51 per treatment arm) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate
• Hormone-refractory disease

• Disease progression after prior hormonal therapy with luteinizing hormone-releasing hormone (LH-RH) analogues or orchiectomy and antiandrogens (given together or consecutively)
• Prostate-specific antigen (PSA) progression documented by at least 2 increases in PSA values over previous PSA reference value

• Must demonstrate continued PSA elevation for at least 6 weeks after discontinuation of antiandrogen therapy
• PSA ≥ 5 ng/mL (Hybritech or equivalent) within the past week
• Testosterone ≤ 0.5 ng/mL* NOTE: *Patients with medical castration with LH-RH analogue must continue with LH-RH analogue throughout the study
• No evidence of painful and/or destructive bone metastases requiring concurrent radiotherapy, bisphosphonates, or bone-seeking radionuclides

• Other bone metastases allowed
• No clinical evidence of brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• WHO 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• WBC ≥ 3,500/mm^3
• Hemoglobin ≥ 10 g/dL

Hepatic

• AST and ALT ≤ 1.5 times upper limit of normal (ULN)
• Bilirubin ≤ ULN
• PTT and PT ≤ 1.5 times ULN OR
• INR ≤ 1.3

Renal

• Creatinine ≤ 1.5 times ULN OR
• Creatinine clearance ≥ 50 mL/min

Cardiovascular

• No unstable angina
• No uncontrolled hypertension
• No deep venous thrombosis within the past 6 months
• No cerebrovascular accident, transient ischemic attack, or myocardial infarction within the past 6 months

Pulmonary

• No pulmonary embolism
• No history of interstitial pneumonitis
• No history of pulmonary fibrosis

Other

• Adequate venous access
• HIV negative
• No active infection
• No pre-existing neuropathy
• No hypersensitivity to phosphorothioates
• No hypersensitivity to oligonucleotides or any other component of the oblimersen formulation or to drugs formulated with polysorbate
• No psychological, familial, sociological, or geographical condition that would preclude study compliance
• No other malignancy within the past 5 years except adequately treated superficial urothelial or skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Prior estramustine allowed
• No other prior chemotherapy
• No concurrent estramustine

Endocrine therapy

• See Disease Characteristics
• At least 6 weeks since prior flutamide, bicalutamide, or nilutamide
• More than 6 weeks since prior hormonal manipulation with PC-SPES
• Concurrent LH-RH agonist allowed
• No concurrent antiandrogens

Radiotherapy

• See Disease Characteristics
• No prior radiotherapy involving > 25% of marrow-producing area
• No prior bone-seeking radionuclides
• No concurrent radiotherapy (including palliative therapy for painful bone metastases)
• No concurrent bone-seeking radionuclides

Surgery

• See Disease Characteristics

Other

• Prior bisphosphonates allowed
• No concurrent anticoagulation except for low-dose warfarin (1 mg/day)
• No concurrent regular (daily) intake of opioid analgesics
• No other concurrent experimental drugs or anticancer drugs
• No concurrent bisphosphonates