Ixabepilone Compared With Mitoxantrone and Prednisone in Treating Patients With Refractory Metastatic Prostate Cancer

Inclusion Criteria:

Histologically confirmed adenocarcinoma of the prostate
Metastatic disease (positive bone scan or measurable disease)

Progressive hormone-refractory disease

Based on 1 of the following:

Transaxial imaging
Rise in prostate-specific antigen (PSA)
Radionuclide bone scan

Must have undergone primary hormonal treatment (e.g., orchiectomy or gonadotropin-releasing hormone analog with or without an antiandrogen) and demonstrated disease progression after antiandrogen discontinuation as defined below:

Two consecutive rising PSA values, obtained at least 2 weeks apart, or documented osseous or soft tissue progression
For patients receiving flutamide, at least 1 PSA value must be obtained at least 4 weeks after flutamide discontinuation
For patients receiving bicalutamide or nilutamide, at least 1 PSA value must be obtained at least 6 weeks after antiandrogen discontinuation
Ineligible if sole manifestation of progression is an increase in disease-related symptoms

Meets 1 of the following criteria:

Measurable disease and an elevated PSA

Nonmeasurable disease and an elevated PSA, as follows:

Positive bone scan
PSA level at least 5 ng/mL, with increases on at least 2 successive occasions at least 2 weeks apart
New metastatic lesions by radionuclide bone scan
Must have received at least 2 courses of paclitaxel- or docetaxel-based therapy, with disease progression documented during therapy or no more than 60 days after cessation of therapy*
Testosterone < 50 ng/dL
No known active brain metastases
Performance status - ECOG 0-2
At least 12 weeks
Granulocyte count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Bilirubin < 1.5 times upper limit of normal (ULN)
AST and ALT < 3 times ULN
Creatinine ≤ 1.5 times ULN
Creatinine clearance > 40 mL/min
Ejection fraction ≥ lower limit of normal by MUGA or echocardiogram
No myocardial infarction within the past 6 months
No significant cardiovascular disease
No New York Heart Association class III or IV congestive heart failure
No active angina pectoris
Fertile patients must use effective contraception before, during, and for 3 months after study therapy
No prior hypersensitivity reaction to agents containing Cremophor®EL
No serious infection
No nonmalignant medical illnesses that are uncontrolled or whose control would be jeopardized by complications of study therapy
No psychiatric illness or social situation that would preclude study compliance
No motor or sensory neuropathy grade 2 or greater

No "currently active" second malignancy except nonmelanoma skin cancer

Patients are not considered to have a "currently active" malignancy provided they have completed therapy and are considered to have less than a 30% risk of relapse
No concurrent prophylactic colony-stimulating factors for myelosuppression
See Disease Characteristics
No more than 1 prior chemotherapy regimen
No prior mitoxantrone or epothilone
No other concurrent chemotherapy
See Disease Characteristics

At least 4 weeks since prior antiandrogens (e.g., flutamide) (6 weeks for bicalutamide or nilutamide)

Patients must continue primary androgen deprivation therapy with luteinizing hormone-releasing hormone agonist during study if prior orchiectomy was not performed
At least 4 weeks since prior systemic (including oral) corticosteroids except corticosteroids as part of first-line chemotherapy tapered off over 10-14 days prior to study entry
At least 4 weeks since any prior hormonal therapy, including megestrol or finasteride
No other concurrent systemic steroids
At least 4 weeks since prior radiotherapy
More than 8 weeks since prior radiopharmaceuticals (e.g., strontium chloride Sr 89 or samarium Sm 153 lexidronam pentasodium)
No concurrent radiotherapy
See Disease Characteristics
At least 4 weeks since prior herbal products known to decrease PSA levels (e.g., Saw Palmetto or PC-SPES)
More than 4 weeks since other prior antiprostate cancer therapy
More than 4 weeks since prior systemic therapies for prostate cancer
No other concurrent investigational agents