Arsenic Trioxide in Treating Patients With Stage IV Prostate Cancer That Has Not Responded to Previous 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