RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Randomized phase II trial to study the effectiveness of combination chemotherapy consisting of paclitaxel, etoposide, and estramustine as compared with ketoconazole plus doxorubicin, vinblastine, and estramustine in treating patients with prostate cancer.

Condition	Treatment or Intervention	Phase
stage II prostate cancer stage III prostate cancer stage IV prostate cancer stage I prostate cancer adenocarcinoma of the prostate recurrent prostate cancer	Drug: doxorubicin  Drug: estramustine  Drug: etoposide  Drug: ketoconazole  Drug: paclitaxel  Drug: vinblastine	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the clinical benefit of two combination chemotherapy regimens, paclitaxel, etoposide, and estramustine vs ketoconazole, doxorubicin, vinblastine, and estramustine in patients with androgen independent prostate cancer, as measured by prostate specific antigen (PSA)-based response rate, time to progression, and overall survival. II. Identify the most promising regimen to use in a phase III trial based on toxic effects, PSA-based response rates, and clinical benefit.

PROTOCOL OUTLINE: This is a randomized multicenter study. Patients are stratified according to risk group: low volume disease (no more than 2 lesions on bone scan), intermediate volume (more than 2 bone lesions confined to axial skeleton), or high volume (bone lesions in appendicular skeletal or visceral lesions). Patients are randomized to one of two treatment arms. Arm I: Patients receive oral estramustine three times a day and oral etoposide twice daily on days 1-14 and paclitaxel IV over 1 hour on day 2. Treatment repeats every 21 days. Arm II: Patients receive doxorubicin IV on days 1, 15, and 29, vinblastine IV on days 8, 22, and 36, oral ketoconazole three times a day on days 1-7, 15-21, and 29-35, and oral estramustine three times a day on days 8-14, 22-28, and 36-42. This regimen consists of 6 weeks of alternating chemotherapy and 2 weeks rest, for an 8 week course. Treatment continues in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 92 patients (46 per treatment arm) will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed adenocarcinoma of the prostate
• Androgen independent disease progression; Castrate testosterone level of less than 40 ng/dL (if medically achieved, treatment must be maintained continuously); Prostate specific antigen (PSA) at least 4 ng/mL and rising on at least 2 consecutive measurements
• No variant histologies such as ductal carcinoma (endometrioid or cribiform) or small cell carcinoma
• Brain metastases controlled

--Prior/Concurrent Therapy--

• Biologic therapy: No prior ketoconazole
• Chemotherapy: No prior doxorubicin, vinblastine, estramustine, paclitaxel, or etoposide; No greater than one prior cytotoxic therapy; No other concurrent chemotherapy; At least 8 weeks since prior mitomycin; At least 60 days since prior suramin
• Endocrine therapy: No antiandrogen therapy such as flutamide or nilutamide within 4 weeks (6 weeks for bicalutamide) without response OR Progression since antiandrogen withdrawal; Prior dexamethasone therapy discontinued
• Radiotherapy: At least 10 weeks since prior strontium Sr 89 and no more than 1 prior regimen; No concurrent strontium Sr 89
• Surgery: Not specified
• Other: No other concurrent therapy for prostate cancer; No concurrent H2 blockers, omeprazole, or antacids; No concurrent terfenadine and astemizole

--Patient Characteristics--

• Age: 18 and over
• Performance status: Zubrod 0-3
• Life expectancy: At least 12 weeks
• Hematopoietic: Absolute neutrophil count at least 1500/mm3; Platelet count at least 100,000/mm3; Hemoglobin greater than 9.5 g/dL (without transfusion support)
• Hepatic: Bilirubin and transaminase less than 2 times the upper limit of normal
• Renal: Creatinine no greater than 2.0 mg/dL OR Estimated creatinine clearance at least 35 mL/min
• Cardiovascular: No clinical history of heart disease; Normal ECG OR Ejection fraction (ECHO, MUGA, or ventriculography) at least 45%
• Other: Spinal cord compression controlled; No active peptic ulcer disease; No active, or likely to become active, second malignancy

Texas
      University of Texas - MD Anderson Cancer Center, Houston,  Texas,  77030,  United States

Study chairs or principal investigators

Randall E. Millikan,  Study Chair,  M.D. Anderson Cancer Center   

Study ID Numbers:  CDR0000065783; MDA-DM-97022; NCI-T97-0023
Record last reviewed:  May 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003084
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08