• Measurable disease response [ Designated as safety issue: No ]
• Overall response [ Designated as safety issue: No ]

• Measurable disease response
• Overall response

RATIONALE: Drugs used in chemotherapy, such as E7389, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase II trial is studying how well E7389 works in treating patients with metastatic prostate cancer that did not respond to hormone therapy.

OBJECTIVES:

Primary

• Determine the number of patients with a > 50% decrease in prostate-specific antigen (PSA) of at least 4 weeks duration in patients with hormone-refractory metastatic prostate cancer treated with E7389.

Secondary

• Estimate the measurable disease response in patients with measurable disease.
• Determine the duration of PSA and measurable disease response.
• Characterize the safety and tolerability of E7389 in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to prior chemotherapy (no prior chemotherapy vs prior taxane only vs 2 prior cytotoxic chemotherapy regimens).

Patients receive E7389 IV over 5 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 5 years.

PROJECTED ACCRUAL: A total of 129 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate

• Progressive (i.e., new lesions on bone scan or new/enlarging lesions on CT scan) or stable metastatic disease*

  • Patients with bone metastases only (i.e., lacking soft tissue disease) must have a prostate-specific antigen (PSA) level ≥ 5 ng/mL within the past 1 week
  • Patients with soft tissue metastases and/or visceral disease must have either measurable disease OR a PSA level ≥ 5 ng/mL within the past 1 week

  • Patients with stable metastases must have a rising PSA level within the past 4 weeks

    • Two consecutive rises in PSA, each measurement taken ≥ 1 week apart NOTE: *Radiologic evidence of hydronephrosis alone is not considered evidence of metastatic disease

• Meets 1 of the following criteria:

  • 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

• Previously treated with bilateral orchiectomy or other primary hormonal therapy with evidence of treatment failure

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

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Granulocyte count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ 1.5 mg/dL
• AST and ALT ≤ 2.5 times upper limit of normal
• Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 40 mL/min
• No active angina pectoris
• No known 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 is allowed if the patient is asymptomatic from a cardiac standpoint
• No peripheral neuropathy > grade 2
• No other prior malignancy (excluding nonmelanomatous skin cancer treated with curative intent) unless the malignancy was treated with curative intent and the patient has been disease free for ≥ 5 years
• No serious concurrent medical illness or active infection that would preclude study treatment
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No more than 2 prior chemotherapy regimens for hormone-refractory disease

  • A taxane-based regimen, mitoxantrone, or other cytotoxic chemotherapy regimen allowed provided there is evidence of disease progression
  • Treatment with estramustine is not considered a separate cytotoxic regimen
• Up to 2 prior noncytotoxic experimental therapies for metastatic disease allowed provided it was given ≥ 4 weeks ago and there is evidence of disease progression
• At least 4 weeks since prior chemotherapy or radiotherapy

• At least 4 weeks since prior flutamide (6 weeks for bicalutamide or nilutamide) and there is continued evidence of disease progression

  • Disease progression after antiandrogen withdrawal must be confirmed by rising PSA after the required 4-6 week washout period (e.g., PSA level higher than the last PSA obtained while on antiandrogen therapy)
• More than 4 weeks since prior and no concurrent estrogen, estrogen-like agents (e.g., PC-SPES, saw palmetto, or other herbal products that may contain phytoestrogens), or any other hormonal therapy (including megestrol, finasteride, ketoconazole, or systemic corticosteroids)
• No prior strontium chloride Sr 89, samarium 153 lexidronam pentasodium, or other radioisotopes

• No concurrent therapeutic anticoagulation with warfarin

  • Unfractionated heparin (standard, low-dose, or adjusted dose) or low molecular weight heparin allowed
• Concurrent bisphosphonates (e.g., pamidronate sodium or zoledronate) allowed provided the patient has been receiving the bisphosphonate for ≥ 4 weeks and there is evidence of disease progression
• No concurrent strong inhibitors or inducers of CYP3A4
• No other concurrent investigational agents
• No other concurrent anticancer therapy, including chemotherapy, gene therapy, biologic therapy, or immunotherapy
• No concurrent palliative radiotherapy