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