RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radioactive substances such as strontium-89 may relieve bone pain associated with prostate cancer. It is not yet known whether chemotherapy is more effective with or without strontium-89 in treating bone metastases.

PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy with or without strontium-89 in treating patients who have prostate cancer that has spread to the bone.

Condition	Treatment or Intervention	Phase
adenocarcinoma of the prostate stage IV prostate cancer recurrent prostate cancer	Drug: docetaxel  Drug: doxorubicin  Drug: estramustine  Drug: ketoconazole  Drug: strontium chloride Sr 89  Drug: vinblastine  Procedure: chemotherapy  Procedure: isotope therapy  Procedure: radiation therapy	Phase III

Further Study Details: 

OBJECTIVES:

• Compare the effectiveness, in terms of overall survival, of consolidation therapy with or without strontium chloride Sr 89 after induction chemotherapy in patients with androgen-independent prostate cancer.

OUTLINE: This is a randomized study. Patients are stratified according to type of induction chemotherapy (KAVE vs estramustine and docetaxel), number of bony metastases (no more than 20 vs more than 20), ECOG performance status (0-1 vs 2-3), and use of zoledronate (yes vs no).

Patients receive one of two induction chemotherapy regimens.

• Regimen A (KAVE): Patients receive doxorubicin IV over 24 hours on day 1 and oral ketoconazole three times a day on days 1-7 of weeks 1, 3, and 5. Patients receive vinblastine IV over 30 minutes on day 1 and oral estramustine three times a day on days 1-7 of weeks 2, 4, and 6. Patients receive no treatment on weeks 7 and 8.
• Patients receive oral estramustine twice a day on days 1-5 and docetaxel IV over 1 hour on day 2 of weeks 1-6. Patients receive no treatment on weeks 7 and 8. Treatment repeats in both regimens every 8 weeks for a total of 2 courses in the absence of disease progression or unacceptable toxicity. Patients with a prostate-specific antigen (PSA) response (at least 50% decline in PSA level from baseline at week 16 OR at least 2 PSA levels decreased at least 50% from baseline) are randomized to one of two treatment arms.
• Arm I: Patients receive doxorubicin IV over 24 hours once weekly for 6 weeks plus strontium chloride Sr 89 IV once at the beginning of chemotherapy.
• Arm II: Patients receive doxorubicin as in arm I. Patients are followed every 3 months.

PROJECTED ACCRUAL: Approximately 680 patients (408 randomized) will be accrued for this study within 34 months.

Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of adenocarcinoma of the prostate
• No small cell carcinoma
• Androgen-independent
• No evidence of response after either of the following anti-androgen withdrawal periods:
• Within 4 weeks for flutamide
• Within 6 weeks for bicalutamide or nilutamide
• Rising prostate-specific antigen (PSA) (at least 5 ng/mL) on at least 2 occasions at least 1 week apart AND bone pain OR worsening bone scan with new lesions in less than 6 months
• Castrate testosterone level no greater than 50 ng/mL (must continue treatment to maintain castrate levels)
• No symptomatic lymphadenopathy (scrotal or pedal edema) or significant local invasive disease (hematuria)
• Osteoblastic metastases on bone scan or CT scan
• No predominant visceral metastases to liver, lungs, or brain

PATIENT CHARACTERISTICS: Age:

• Any age

Performance status:

• Zubrod 0-3

Life expectancy:

• At least 12 weeks

Hematopoietic:

• WBC greater than 3,000/mm^3
• Absolute neutrophil count greater than 1,500/mm^3
• Platelet count greater than 100,000/mm^3

Hepatic:

• Bilirubin no greater than 2 times upper limit of normal (ULN)
• AST and ALT no greater than 2 times ULN

Renal:

• Not specified

Cardiovascular:

• No transient ischemic attack or myocardial infarction within the past 12 months
• No active angina or claudication sufficient to limit activity
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other:

• Fertile patients must use effective contraception
• No prior allergic reaction to compounds of similar biologic or chemical composition to study drugs
• No other conditions (e.g., pernicious anemia) associated with achlorhydria
• No other active malignancy or malignancy that is likely to become active except non-melanoma skin cancer
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study participation
• No other uncontrolled concurrent illness that would preclude study participation

PRIOR CONCURRENT THERAPY: Biologic therapy:

• At least 4 weeks since prior immunotherapy and recovered
• Prior angiogenesis inhibitors and gene therapy allowed

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• No prior doxorubicin or vinblastine for patients receiving induction chemotherapy with KAVE (ketoconazole, doxorubicin, vinblastine, estramustine)
• No prior docetaxel for patients receiving induction chemotherapy with estramustine plus docetaxel

Endocrine therapy:

• See Disease Characteristics
• Prior secondary hormonal agents (e.g., aminoglutethimide, diethylstilboestrol, or estramustine) allowed
• Prior steroid therapy (e.g., dexamethasone, prednisone, or hydrocortisone) allowed

Radiotherapy:

• At least 4 weeks since prior radiotherapy and recovered
• No prior strontium chloride Sr 89 or samarium Sm 153 lexidronam pentasodium

Surgery:

• No prior vagotomy

Other:

• No more than 1 prior cytotoxic regimen
• No prior ketoconazole for patients receiving induction chemotherapy with KAVE

Iowa
      Genesis Regional Cancer Center at Genesis Medical Center, Davenport,  Iowa,  52804,  United States; Recruiting
Texas
      MD Anderson Cancer Center at University of Texas, Houston,  Texas,  77030-4009,  United States; Recruiting

Study chairs or principal investigators

Shi-Ming Tu, MD,  Study Chair,  M.D. Anderson Cancer Center   

Study ID Numbers:  CDR0000068897; MDA-ID-00156; NCI-3410; NCT00024167
Record last reviewed:  December 2004
Last Updated:  February 7, 2005
Record first received:  September 13, 2001
ClinicalTrials.gov Identifier:  NCT00024167
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08