RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of arsenic trioxide in treating patients who have stage IV prostate cancer that has not responded to hormone therapy.

OBJECTIVES:

• Determine the efficacy of arsenic trioxide in patients with metastatic stage IVA or IVB hormone-refractory prostate cancer.
• Determine the toxicity of this drug in this patient population.
• Assess, in a preliminary manner, the effect of this drug on pain control in these patients.
• Assess the potential value of serial quantitative prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) mRNA determinations in RNA from peripheral blood mononuclear cells as surrogate markers of disease response in patients treated with this drug.
• Assess the pharmacokinetics and pharmacodynamics of this drug in these patients.
• Assess the feasibility of using pretreatment bone marrow evaluation of PSA and PMSA mRNA levels and pi class glutathione S-transferase expression (i.e., eliminate glutathione levels) as potential correlates of disease response in patients treated with this drug.

OUTLINE: Patients receive arsenic trioxide IV over 2 hours on days 1-5 and 8-12 for one course. Treatment continues as biweekly infusions for at least 14 additional weeks in the absence of disease progression, unacceptable toxicity, or excessive increase in serum prostate-specific antigen.

Pain is assessed at baseline and then before each biweekly treatment.

PROJECTED ACCRUAL: A total of 17-37 patients will be accrued for this study within 12-24 months.

DISEASE CHARACTERISTICS:

• Diagnosis of stage IVA or IVB hormone-refractory prostate cancer

  • Evidence of metastatic disease by physical exam, bone scan, abdominal or pelvic CT scan, or chest X-ray
  • Must have failed at least 2 prior hormonal therapy regimens (e.g., luteinizing hormone-releasing hormone [LHRH] agonist plus antiandrogen and antiandrogen withdrawal)
  • Must have 2 successive increases in serum prostate-specific antigen (PSA) levels to at least 10 ng/mL measured at least 2 weeks apart
  • Must have castrate testosterone levels (no greater than 50 ng/dL) due to prior orchiectomy or continuing LHRH agonist therapy
• Obstructive uropathy and/or hydronephrosis allowed if adequate renal function and urinary drainage

PATIENT CHARACTERISTICS:

Age:

• Any age

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 2,500/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9.0 g/dL

Hepatic:

• Bilirubin less than 2 mg/dL
• Transaminases less than 2.5 times upper limit of normal

Renal:

• See Disease Characteristics
• Creatinine less than 2 mg/dL
• Potassium between 4.0 and 5.5 mEq/L OR
• Magnesium between 1.5 and 2.5 mEq/L

Cardiovascular:

• No second-degree heart block without permanent pacemaker
• QT interval under 500 milliseconds

Other:

• No significant active infectious disease
• No grade 2 or greater peripheral neuropathy
• No other debilitating acute or chronic co-morbid medical, neurological, or psychiatric condition that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas and 8 weeks for suramin) and recovered

Endocrine therapy:

• See Disease Characteristics
• At least 4 weeks since prior antiandrogen therapy (6 weeks for bicalutamide) (if PSA is increased from baseline)
• At least 2 weeks since prior corticosteroid therapy and recovered

Radiotherapy:

• At least 2 weeks since prior radiotherapy (4 weeks for strontium chloride Sr 90) and recovered

Surgery:

• See Disease Characteristics
• Recovered from prior surgery

Other:

• Recovered from acute toxicity of prior therapy
• At least 3 weeks since prior bisphosphonates
• No concurrent amphotericin B or other agent that prevents restoration of potassium or magnesium to normal levels and/or correction of QT interval to under 500 milliseconds