Treating Patients With Metastatic Prostate Cancer Not Responding to Hormone and Chemotherapy

You may be eligible if

• Histologically confirmed adenocarcinoma of the prostate
• Progressive metastatic disease (i.e., positive bone scan or measurable disease) despite castrate levels of testosterone (either from orchiectomy or luteinizing hormone-releasing hormone \[LHRH\] agonist therapy)
• * Progressive disease after discontinuing hormonal therapy
• * Progressive disease is based on any of the following\*:
• * Transaxial imaging
• * Rise in prostate-specific antigen (PSA)
• * Radionuclide bone scan (must show new metastatic lesions)
• Nonmeasurable or measurable disease
• * For measurable disease, progression is defined by RECIST criteria
• * Positive bone scan and elevated PSA required for nonmeasurable disease
• * PSA evidence of progressive prostate cancer during or after first-line chemotherapy consists of a PSA level ≥ 2 ng/mL that has risen on ≥ 2 successive occasions ≥ 1 week apart
• Received ≥ 3 prior courses of paclitaxel- or docetaxel-based therapy, with disease progression documented during therapy or after cessation of therapy
• * No more than 1 prior chemotherapy regimen
• * Re-treatment with the same taxane-based regimen allowed
• * Changes in prior chemotherapy regimen (addition of other agents) for disease progression are considered 2 chemotherapy regimens, and are not allowed
• PSA ≥ 2 ng/mL
• Testosterone \< 50 ng/dL
• * Patients must continue primary androgen deprivation with LHRH analogue if they have not undergone orchiectomy
• No known active brain metastases
• ECOG performance status 0-2
• Life expectancy ≥ 12 weeks
• Creatinine ≤ 1.5 times upper limit of normal (ULN) OR creatinine clearance \> 40 mL/min
• ALT and AST \< 2.5 times ULN
• Granulocyte count ≥ 2,000/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin \< 1.5 times ULN
• Ejection fraction normal by MUGA scan or echocardiogram
• No significant cardiovascular disease, including any of the following:
• * Congestive heart failure (New York Heart Association class III-IV heart disease)
• * Active angina pectoris
• * Myocardial infarction within the past 6 months
• No serious infections or nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by study therapy
• No psychiatric illness or social situation that would preclude study compliance
• No pre-existing motor or sensory peripheral neuropathy \> grade 1
• No known prior severe hypersensitivity reactions to agents containing Cremophor® EL
• No "currently active" second malignancy other than nonmelanoma skin cancer
• * Patients are not considered to have a "currently active" malignancy if they have completed therapy and are considered to be at \< 30% risk of relapse
• Fertile patients must use effective contraception prior to, during, and for 3 months after completion of study treatment
• See Disease Characteristics
• No prior mitoxantrone hydrochloride, ixabepilone, or other epothilones
• At least 4 weeks since prior hormonal therapy (i.e., any dose of megestrol, finasteride, or any herbal product known to decrease PSA levels \[e.g., saw palmetto or PC-SPES\]) other than LHRH agonist or a stable dose of corticosteroids from a prior chemotherapy regimen
• More than 4 weeks since other prior systemic therapies for prostate cancer
• At least 4 weeks since prior radiation therapy
• More than 8 weeks since prior radiopharmaceuticals (e.g., strontium chloride Sr 89 or samarium Sm 153 lexidronam pentasodium)
• No concurrent moderate to strong CYP3A4 inhibitors
• No concurrent prophylactic colony-stimulating factors
• No concurrent radiotherapy