A Phase III Randomized Trial for Evaluating Second Line Hormonal Therapy (Ketoconazole/Hydrocortisone) Versus Paclitaxel/Estramustine Combination Chemotherapy on Progression Free Survival in Asymptomatic Patients With a Rising PSA After Hormonal Therapy for Prostate Cancer

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed adenocarcinoma of the prostate that was continuously treated
with androgen suppression

- Rising prostate-specific antigen (PSA), defined as PSA > 5 ng/mL, rising on 2
consecutive measurements at least 4 weeks apart

- Gleason score 7 or higher and/or seminal vesicle involvement at diagnosis

- Patients previously treated with antiandrogen or glucocorticoid therapy must meet the
following criteria:

- Must show a continued rise in PSA after stopping antiandrogen (flutamide,
bicalutamide, or nilutamide) or glucocorticoid (dexamethasone or prednisone)

- At least 4 weeks continued rise in PSA after flutamide or nilutamide (6
weeks for bicalutamide)

- Testosterone less than 50 ng/dL

- Patients who have not undergone surgical castration must continue primary
androgen suppression to maintain castrate levels of testosterone

- No progressive or measurable local or metastatic disease (including bone metastases)

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- ECOG 0-1

Life expectancy:

- Not specified

Hematopoietic:

- Granulocyte count at least 2,000/mm^3

- Platelet count at least 100,000/mm^3

Hepatic:

- SGOT no greater than 2 times upper limit of normal

- Bilirubin no greater than 1.5 mg/dL

Renal:

- Creatinine no greater than 1.7 mg/dL

Cardiovascular:

- No American Heart Association class III or IV heart disease

- No uncontrolled congestive heart failure

- No life-threatening cardiac arrhythmias

Other:

- Fertile patients must use effective contraception

- No other prior malignancy unless curatively treated and disease-free for appropriate
time period for specific cancer

- No preexisting peripheral neuropathy greater than grade 1

- No known hypersensitivity to polysorbate 80

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- Not specified

Chemotherapy:

- At least 5 years since prior systemic chemotherapy

Endocrine therapy:

- See Disease Characteristics

- At least 4 weeks since prior hydrocortisone

- No prior ketoconazole

Radiotherapy:

- At least 28 days since prior radiotherapy to primary site

- No prior palliative radiotherapy

- No concurrent radiotherapy

Surgery:

- See Disease Characteristics

Other:

- Recovered form prior therapy

- At least 7 days since prior parenteral antibiotics for active infection

- No concurrent digitalis

- No concurrent H_2 blockers or proton pump inhibitors (arm I only)

- Concurrent bisphosphonates allowed provided they were initiated prior to study
therapy