RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving more than one drug may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy in treating patients who have prostate cancer that has not responded to hormone therapy.

Condition	Treatment or Intervention	Phase
stage II prostate cancer Pain stage III prostate cancer stage IV prostate cancer stage I prostate cancer adenocarcinoma of the prostate recurrent prostate cancer	Drug: cyclophosphamide  Drug: docetaxel  Drug: doxorubicin  Drug: filgrastim	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the PSA response, duration of PSA response, disease free survival, median survival, and overall survival in patients with chemotherapy naive hormone refractory adenocarcinoma of the prostate treated with doxorubicin and cyclophosphamide with sequential docetaxel. II. Assess for any improvement in pain over time in patients treated with this regimen.

PROTOCOL OUTLINE: This is a multicenter study. Patients receive doxorubicin IV over 3-5 minutes and cyclophosphamide IV on days 1, 22, 43, and 64, and docetaxel IV over 1 hour on days 85, 106, and 127 in the absence of disease progression or unacceptable toxicity. Patients receive filgrastim (G-CSF) subcutaneously daily beginning 24 hours after completion of chemotherapy infusions and continuing until blood counts recover. G-CSF must be discontinued at least 24 hours prior to starting subsequent chemotherapy infusions. Pain and analgesic use are assessed before study, every 3 weeks during study, after completion of study, and then at 3 months after completion of study. Patients are followed every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter until death.

PROJECTED ACCRUAL: Approximately 42-105 patients will be accrued for this study over 18 months.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven adenocarcinoma of the prostate that is chemotherapy naive and refractory to hormonal therapy with combined androgen blockade; No concurrent antiandrogen therapy withdrawal: Must continue antiandrogen therapy until completion of study OR Must discontinue flutamide at least 4 weeks before or bicalutamide at least 8 weeks before study enrollment, and must have disease progression off antiandrogen therapy, defined by serial increase in PSA (at least 2 measurements taken at least 2 weeks apart) or measurable tumor; Concurrent LHRH antagonist allowed if no prior orchiectomy; No minimum PSA level required
• Measurable or evaluable disease; An increase in PSA or pain without measurable or evaluable disease does not constitute hormone refractory disease

--Prior/Concurrent Therapy--

• Biologic therapy: No concurrent WBC transfusions; No other concurrent biologic therapy
• Chemotherapy: See Disease Characteristics; No other concurrent chemotherapy
• Endocrine therapy: See Disease Characteristics
• Radiotherapy: At least 4 weeks since prior radiotherapy
• Surgery: See Disease Characteristics
• Other: No other concurrent investigational agent; No concurrent acetaminophen for fever prophylaxis

--Patient Characteristics--

• Age: 18 and over
• Performance status: Karnofsky 60-100%; ECOG 0-2
• Life expectancy: At least 6 months
• Hematopoietic: Absolute neutrophil count at least 1,500/mm3; Platelet count at least 100,000/mm3; Hemoglobin at least 10 g/dL
• Hepatic: SGOT and SGPT no greater than 2 times upper limit of normal; Bilirubin no greater than 2.0 mg/dL
• Renal: Creatinine no greater than 2.0 mg/dL
• Cardiovascular: LVEF normal; No impaired cardiac status (e.g., history of severe heart disease, cardiomyopathy, or congestive heart failure)
• Other: No active infection, defined by the following: Clinical syndrome consistent with a viral or bacterial infection (e.g., influenza, upper respiratory infection, or urinary tract infection); Fever with a clinical site of infection identified; Microbiologically documented infection including, but not limited to, bacteremia or septicemia; HIV negative; No other malignancy within the past 5 years except surgically cured basal cell or squamous cell skin cancer; No psychiatric, addictive, or other disorder that would preclude informed consent or compliance; No hypersensitivity to E. coli derived proteins or drugs formulated with polysorbate 80 (e.g., human insulin)

California
      Wilshire Oncology Medical Group, Inc., Los Angeles,  California,  90057,  United States
Florida
      Geffen Cancer Center and Research Institute, Vero Beach,  Florida,  32960-6541,  United States
New York
      Arena Oncology Associates, Great Neck,  New York,  11021,  United States
      New York Medical College, Valhalla,  New York,  10595,  United States
North Carolina
      N.W. Carolina Oncology & Hematology, P.A., Hickory,  North Carolina,  28603,  United States
Pennsylvania
      Associates of Hematology/Oncology, Upland,  Pennsylvania,  19013,  United States

Study chairs or principal investigators

Debra Litwak,  Study Chair,  Amgen   

Study ID Numbers:  CDR0000067942; AMGEN-GCSF-980282; NCI-V00-1595
Record last reviewed:  June 2004
Last Updated:  October 13, 2004
Record first received:  July 5, 2000
ClinicalTrials.gov Identifier:  NCT00005960
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08