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

Inclusion Criteria: * 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