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.

Eligibility Criteria:

• Diagnosis of stage IVA or IVB hormone-refractory prostate cancer
• Obstructive uropathy and/or hydronephrosis allowed if adequate renal function and urinary drainage
• 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
• Bilirubin less than 2 mg/dL

Exclusion Criteria:

• 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
• 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