• Measurable disease response as defined by RECIST criteria [ Designated as safety issue: No ]
• Overall response [ Designated as safety issue: No ]

• Measurable disease response as defined by RECIST criteria
• Overall response

RATIONALE: Drugs used in chemotherapy, such as ixabepilone, work in different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: This phase II trial is studying how well ixabepilone works in treating patients with metastatic prostate cancer that has not responded to previous hormone therapy.

OBJECTIVES:

Primary

• To determine the effect on percent with a 50% decrease in PSA response in patients with metastatic prostate cancer who have progressed on androgen ablation therapy and are classified into 1 of 3 separate categories:

  • Never received prior chemotherapy/cytotoxic therapy
  • Received prior taxane-based regimen
  • Received 2 prior cytotoxic chemotherapy regimens (including, but not limited to, prior taxane and anthracyclines)

Secondary

• Determine measurable disease response in patients with measurable disease treated with this drug and overall response rate.
• Determine the toxic effects of this drug in these patients.
• Determine the duration of PSA and measurable disease response in patients treated with this drug.
• Determine the expression of p53, multidrug resistance protein, and Bcl-2 by immunohistochemistry in the primary tumors of patients treated with this drug.

OUTLINE: This is a multicenter study. Patients are stratified according to prior chemotherapy (none vs 1 prior taxane-containing regimen vs 2 prior cytotoxic regimens).

Patients receive ixabepilone IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 83 patients (27 for the no prior chemotherapy stratum; 27 each for the 2 prior cytotoxic chemotherapy regimens and prior docetaxel strata) will be accrued for this study within 8-22 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate

  • Metastatic disease

• Evidence of disease progression (e.g., new lesions on bone scan or new/enlarging lesions on CT scan) OR rising prostate-specific antigen (PSA) within the past 4 weeks

  • Radiologic evidence of hydronephrosis alone is not considered evidence of metastatic disease (e.g., increasing PSA)
  • Patients with bone metastases only (i.e., lacking soft tissue disease) must have a PSA level ≥ 10 ng/mL within the past week
  • Patients with soft tissue metastasis and/or visceral disease must have measurable disease OR a PSA level ≥ 10 ng/mL within the past week

  • Patients with stable disease and rising PSA must show 2 consecutive rises in PSA measurements taken at least 2 weeks apart

    • Most recent PSA level must be obtained within the past 4 weeks
  • Disease progression after prior anti-androgen withdrawal must be confirmed by a rising PSA after the 4-6 week washout period (e.g., PSA level higher than the last PSA obtained while on anti-androgen therapy)

• Failed prior bilateral orchiectomy or other primary hormonal therapy

  • Patients who have not undergone bilateral orchiectomy must continue on luteinizing hormone-releasing hormone (LHRH) agonist therapy (e.g., leuprolide or goserelin) or LHRH antagonist (e.g., abarelix) during study treatment AND must have a serum testosterone level ≤ 50 ng/dL within the past 4 weeks to confirm androgen suppression
• No carcinomatous meningitis or brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• WBC ≥ 4,000/mm^3

Hepatic

• SGPT ≤ 2 times upper limit of normal
• Bilirubin ≤ 1.5 mg/dL
• INR normal

Renal

• Creatinine ≤ 1.5 mg/dL OR
• Creatinine clearance ≥ 50 mL/min

Cardiovascular

• No active angina pectoris
• No New York Heart Association class III-IV heart disease
• No myocardial infarction within the past 6 months

• No evidence of ventricular dysrhythmias or other unstable arrhythmia

  • Rate-controlled atrial fibrillation allowed provided the patient is asymptomatic

Other

• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except curatively treated nonmelanoma skin cancer
• No peripheral neuropathy > grade 1
• No serious medical illness or active infection that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent prophylactic filgrastim (G-CSF)

Chemotherapy

• No more than 2 prior cytotoxic chemotherapy regimens for hormone-refractory disease
• At least 4 weeks since prior chemotherapy with a taxane-based regimen, mixantrone, or another cytotoxic chemotherapy regimen provided there is evidence of progressive disease

Endocrine therapy

• See Disease Characteristics
• At least 4 weeks since prior flutamide AND continued evidence of progressive disease
• At least 6 weeks since prior bicalutamide or nilutamide AND continued evidence of progressive disease
• At least 4 weeks since prior estrogen or estrogen-like agents (e.g., PC-SPES, saw palmetto, or other herbal products which may contain phytoestrogens)
• At least 4 weeks since prior hormonal therapy, including megestrol, finasteride, ketoconazole, or systemic corticosteroids
• No concurrent estrogen or estrogen-like agents (e.g., PC-SPES, saw palmetto, or other herbal products which may contain phytoestrogens)
• No concurrent hormonal therapy, including megestrol, finasteride, ketoconazole, or systemic corticosteroids

Radiotherapy

• More than 4 weeks since prior radiotherapy
• No prior strontium chloride Sr 89 or samarium Sm 153 lexidronam pentasodium
• No other prior radioisotope
• No concurrent radiotherapy for pain control

Surgery

• See Disease Characteristics

Other

• No more than 1 prior experimental (non-cytotoxic) therapy AND evidence of progressive disease
• At least 4 weeks since prior experimental therapy
• Concurrent bisphosphonates (e.g., pamidronate or zoledronate) allowed provided treatment was initiated at least 4 weeks ago and there is evidence of progressive disease

• No concurrent therapeutic warfarin

  • Concurrent prophylactic or therapeutic doses of low molecular weight heparin allowed provided criterion for INR is met
• No other concurrent investigational agents