Dexamethasone, Aspirin, and Diethylstilbestrol in Treating Patients With Locally Advanced or Metastatic Prostate Cancer

OBJECTIVES:

Primary

• Compare the prostate-specific antigen (PSA) response in patients with locally advanced or metastatic prostate cancer treated with dexamethasone and aspirin with delayed vs immediate diethylstilbestrol.

Secondary

• Compare the overall response rate in patients treated with these regimens.
• Compare the quality of life of patients treated with these regimens.
• Compare the progression-free and overall survival of patients treated with these regimens.

OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified according to ECOG performance status (0 vs 1-3), prostate-specific antigen (PSA) response to prior therapy (PSA normalization vs inability to normalize), and bone scan (positive vs negative for bony metastases). Patients are randomized to 1 of 2 treatment arms.

• Arm I (deferred diethylstilbestrol): Patients receive oral dexamethasone and oral acetylsalicyclic acid once daily (DA). Subsequent to treatment failure with DA, patients continue to receive DA as before in addition to oral diethylstilbestrol once daily (DAS). Treatment with DAS continues in the absence of disease progression or unacceptable toxicity.
• Arm II (immediate diethylstilbestrol): Patients receive oral dexamethasone, oral acetylsalicyclic acid, and oral diethylstilbestrol once daily (DAS). Treatment continues in the absence of disease progression or unacceptable toxicity.

Quality of life is evaluated monthly during study treatment.

After completion of study treatment, patients are followed every 3 months for 1 year and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 260 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of adenocarcinoma of the prostate

• Elevated prostate-specific antigen (PSA)
• Failed previous treatments, including gonadatropan regulatory hormone analogue therapy, radiotherapy, surgery, or any combination of these
• Biochemically castrate (testosterone < 1 nmol/L) at baseline

PATIENT CHARACTERISTICS:

• Life expectancy ≥ 3 months
• ECOG performance status 0-3
• WBC ≥ 3,000/mm^3
• Absolute neutrophil count (neutrophils and bands) ≥ 2,000/mm^3
• Platelet count ≥ 50,000/mm^3
• Bilirubin ≤ 2 times upper limit of normal (ULN)
• AST or ALT ≤ 3 times ULN
• Creatinine ≤ 1.5 times ULN
• Able to swallow tablets
• No other malignancy within the past 3 years except basal cell skin cancer
• No previous thromboembolic disease, including stroke, venous or arterial thrombosis, and myocardial infarction with ongoing angina pectoris

• Prior uncomplicated myocardial infarction allowed
• No diabetes mellitus if treatment titration is thought to be difficult or inappropriate
• No active gastric or duodenal ulcer

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Prior concurrent bisphosphonates allowed
• No concurrent investigational agents or participation in another investigational drug study
• No other concurrent antineoplastic therapy, including new estrogen therapy, radiation therapy, or PC-SPES
• No other concurrent corticosteroids (e.g., dexamethasone for nausea or vomiting) except those prescribed in the study regimen