A Phase II Study of 3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone (3-AP, Triapine) in Patients With Advanced Prostate Cancer
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of hormone-refractory metastatic prostate cancer by one of the following
methods:
- Measurable disease
- PSA level of at least 5 ng/mL with a positive bone scan
- Objective evidence of progressive metastatic disease in the past 3 months defined by
any of the following:
- An increase in PSA value of at least 25% (minimum absolute increase of 5 ng/mL)
on at least 2 successive occasions, at least 2 weeks apart
- A new symptomatic lesion on bone scan
- A new metastases not in bone
- Growth of existing non-bone measurable metastatic disease NOTE: An increase in
pain or symptoms alone without other evidence of progression, or elevation of
PSA or serum alkaline phosphatase alone without evidence of metastatic disease
is not sufficient
- Prior bilateral orchiectomy or other primary hormonal treatment with evidence of
treatment failure
- Patients with no prior bilateral orchiectomy must have a testosterone level less
than 50 ng/mL and must continue leuteinizing hormone-releasing hormone therapy
while on study
- No known active CNS metastases (excluding prior CNS metastases with currently stable
disease after treatment )
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-2
Life expectancy
- More than 3 months
Hematopoietic
- WBC at least 3,000/mm^3
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- Hemoglobin at least 10 g/dL (transfusion allowed)
Hepatic
- Bilirubin no greater than 2.0 mg/dL
- ALT/AST no greater than 5 times upper limit of normal
- Albumin greater than 2.5 g/dL
- Chronic hepatitis allowed
Renal
- Creatinine no greater than 2.0 mg/dL
Cardiovascular
- No myocardial infarction within the past 3 months
- No unstable angina
- No uncontrolled arrhythmias
- No uncontrolled congestive heart failure
Pulmonary
- No dyspnea at rest
Other
- Nutrition adequate (caloric intake considered adequate for maintenance of weight)
- Fertile patients must use effective contraception
- No prior or concurrent malignancies except for non-metastatic basal cell or squamous
cell skin cancer or any stage I malignancy curatively resected more than 5 years ago
- No active uncontrolled infectious process
- No other life-threatening illness
- No peripheral neuropathy greater than grade 2
PRIOR CONCURRENT THERAPY:
Biologic therapy
- At least 2 weeks since prior biologic therapy
Chemotherapy
- At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and
recovered
- No more than 1 prior chemotherapy regimen for metastatic disease
Endocrine therapy
- See Disease Characteristics
- At least 4 weeks since other prior hormonal therapy including any of the following:
- Megestrol
- Finasteride
- Herbal products known to decrease PSA levels (e.g., saw palmetto and PC-SPES)
- Systemic corticosteroids
- At least 4 weeks since prior flutamide therapy (6 weeks for bicalutamide or
nilutamide) with continued evidence of progressive disease documented by at least 1
PSA value after discontinuation
Radiotherapy
- At least 8 weeks since prior radiopharmaceuticals (strontium chloride Sr 89, samarium
Sm 153 lexidronam pentasodium)
- At least 4 weeks since prior radiotherapy and recovered
Surgery
- See Disease Characteristics
- At least 3 weeks since prior major surgery and recovered
Other
- No other concurrent investigational agents
- No other concurrent anticancer treatment