Combination Chemotherapy Plus Bevacizumab in Treating Patients With Metastatic Prostate Cancer

Inclusion Criteria:

Patients must have histologically documented adenocarcinoma of the prostate with progressive systemic (metastatic) disease despite castrate levels of testosterone due to orchiectomy or LHRH agonist (which must be continued); castrate levels of testosterone must be maintained

At the time of enrollment, patients must have evidence of metastatic disease, either:

Measurable disease (with any PSA) OR
Non-measurable disease with PSA >= 5 ng/ml; patients with PSA >= 5 ng/ml only are not eligible DEFINITION OF MEASURABLE DISEASE/TARGET LESIONS
Any lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques: 1) physical exam for clinically palpable lymph nodes and superficial skin lesions, 2) chest X-ray for clearly defined lung lesions surrounded by aerated lung OR those lesions measured as >= 10 mm with a spiral CT scan or MRI

Measurable lesions (up to a maximum of 10 in number) representative of all organs involved to be identified as target lesions; the sum of the longest diameters (LD) for all target lesions will be calculated and reported as baseline sum LD

If measurable disease is confined to a solitary lesion then its neoplastic nature will need to be confirmed by histology
Ultrasound may not be used to measure tumor lesions that are not easily accessible clinically DEFINITION OF NON-MEASURABLE DISEASE/NON-TARGET LESIONS

Non-target lesions include all other lesions, including small lesions with longest diameter < 20 mm with conventional techniques or < 10 mm with spiral CT scan and truly non-measurable lesions, which include:

Bone lesions
Pleural or pericardial effusions, ascites
CNS lesions, leptomeningeal disease
Irradiated lesions, unless progression documented after RT

Patients must have demonstrated evidence of progressive disease since the most recent change in therapy; progressive disease is defined as any one of the following (measurable disease, bone scan, or PSA progression):

MEASURABLE DISEASE PROGRESSION: Objective evidence of increase > 20% in the sum of the longest diameters (LD) of target lesions from the time of maximal regression or the appearance of one or more new lesions
BONE SCAN PROGRESSION: Appearance of one or more new lesions on bone scan attributable to prostate cancer along with a PSA >= 5 ng/ml will constitute progression
PSA PROGRESSION: An elevated PSA (at least >= 5 ng/ml) which has risen serially from baseline on two occasions each at least one week apart. If the confirmatory PSA (#3) value is less (i.e., #3b) than screening PSA (#2) value, then an additional test for rising PSA (#4) will be required to document progression
Failure despite standard androgen deprivation therapy
Flutamide and megestrol acetate (any dose) must be discontinued at least 4 weeks prior to registration; bicalutamide and nilutamide must be discontinued at least 6 weeks prior to registration. If improvement following antiandrogen withdrawal is noted, progression must be established using the criteria above; primary testicular androgen suppression (e.g., with an LHRH analogue) should not be discontinued
At least 4 weeks since any hormonal therapy, including ketoconazole, aminoglutethimide, systemic steroids (any dose), megestrol acetate (any dose)
No prior cytotoxic chemotherapy, including estramustine or suramin
No prior anti-angiogenesis agents, including thalidomide and bevacizumab
>= 4 weeks since major surgery and fully recovered
>= 4 weeks since any prior radiation and fully recovered
>= 8 weeks since the last dose of strontium-89 or Samarium
Patients receiving bisphosphonate therapy prior to initiating protocol treatment must have received bisphosphonates for at least 1 month and have progressive disease despite this therapy
CTC (ECOG) performance status: 0-2
No myocardial infarction or significant change in anginal pattern within one year or current congestive heart failure (NYHA Class 2 or higher)
No deep venous thrombosis or pulmonary embolus within one year. No need for full-dose oral or parenteral anticoagulation; daily prophylactic aspirin is allowed
No clinically significant peripheral neuropathy
Granulocytes >= 1500/ul
Platelet count >= 100,000/ul
Creatinine =< 1.5 x upper limit of normal
Bilirubin =< 1.0 x upper limit of normal
AST =< 1.5 x upper limits of normal
Urinalysis =< 1 + protein on dipstick
PSA >= 5 ng/ml (if non-measurable disease)
Serum Testosterone =< 50 ng/ml for patients who have not had bilateral orchiectomy