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