A Randomized Phase II Trial of Mitoxantrone, Estramustine and Navelbine or 13-cis Retinoic Acid, Interferon and Paclitaxel in Patients With Metatstatic Hormone Refractory Prostate Cancer

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed adenocarcinoma of the prostate

- Evidence of progressive metastatic disease (e.g., bone, pelvic mass, lymph node,
liver or lung metastases)

- Radiologic evidence of hydronephrosis only does not constitute evidence of
metastatic disease

- Must not have an elevated serum alkaline phosphatase or PSA level as only evidence of
disease

- If bone metastases only (i.e., lacking soft tissue disease), must have PSA level of
at least 20 ng/mL

- If soft tissue metastases and/or visceral disease, must have either bidimensionally
measurable disease or PSA level of at least 20 ng/mL

- Must have had prior bilateral orchiectomy or other primary hormonal therapy (e.g.,
estrogen therapy or LHRH blocker plus flutamide) with evidence of treatment failure

- No carcinomatous meningitis or brain metastases

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- ECOG 0-2

Life expectancy:

- Not specified

Hematopoietic:

- WBC at least 4,000/mm^3

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

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

Hepatic:

- See Disease Characteristics

- Bilirubin no greater than 1.5 mg/dL

- SGOT/SGPT no greater than 2 times upper limit of normal

Renal:

- Creatinine no greater than 2.0 mg/dL OR

- Creatinine clearance at least 50 mL/min

Cardiovascular:

- No active angina pectoris

- No New York Heart Association class III or IV heart disease

- No myocardial infarction within the past 6 months

- No deep venous thrombosis

- LVEF at least 50% by MUGA

Other:

- Fertile patients must use effective contraception during and for 1 month after study

- Prior malignancy allowed provided curatively treated and disease free for appropriate
time period for specific cancer

- No other serious medical illness or active infection that would preclude protocol
therapy

- No concurrent prolonged exposure to sunlight

- No concurrent alcohol consumption

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- Not specified

Chemotherapy:

- No prior chemotherapy, including neoadjuvant chemotherapy or single-agent
estramustine

Endocrine therapy:

- See Disease Characteristics

- If no prior bilateral orchiectomy, must continue LHRH agonist therapy (e.g., depot
leuprolide or goserelin)

- At least 4 weeks since prior flutamide or flutamide with evidence of progressive
disease

- At least 6 weeks since prior bicalutamide with evidence of progressive disease

Radiotherapy:

- More than 4 weeks since prior radiotherapy

- No prior strontium chloride Sr 89, samarium Sm 153 lexidronam pentasodium, or other
radioisotope therapies

Surgery:

- See Disease Characteristics

Other:

- Recovered from all toxic effects due to prior treatment for prostate cancer

- No concurrent milk, milk products, antacids, calcium-containing drugs, or any food
with estramustine (arm I only)

- No concurrent vitamin supplements containing vitamin A (arm II only)