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