Digoxin for Recurrent Prostate Cancer

Inclusion Criteria: * There must be a confirmed biochemical progression. Biochemical progression is defined as three rises in PSA levels, with each PSA determined at least 4 weeks apart, and each PSA value increase \>0.2 ng/ml. * Baseline PSA must be determined within 4 weeks of study entry. At least 3 PSA values are necessary prior to the study entry to calculate PSA doubling time (PSADT) calculator. * Men with history of radical prostatectomy are required to have baseline PSA \>1 ng/ml. Men treated with primary radiation therapy are required to have baseline PSA\>2 ng/ml and greater than 150% rise from postradiation nadir. * PSA doubling time must be between 6 and 24 months. * All treatments including intermittent hormonal therapy must have been discontinued for \> 6 months prior to study entry. * No clinical or radiological evidence of distant metastases * ECOG \< 2 and adequate organ function * Men with history of radical prostatectomy are required to have baseline PSA \>1 ng/ml. Men treated with primary radiation therapy are required to have baseline PSA\>2 ng/ml and greater than 150% rise from postradiation nadir * Baseline PSA must be determined within 4 weeks of study entry. At least 3 PSA values are necessary to calculate PSA doubling time via PSADT calculator at: http://www.mskcc.org/mskcc/applications/nomograms/PSADoublingTime.aspx. PSA doubling time must be between 6 and 24 months. * All previous local modalities of treatment, including radiation and surgery, must have been discontinued at least 8 weeks prior to treatment in this study. Patients may have received prior systemic chemotherapy, hormonal therapy, biologic or vaccine therapy. All systemic treatments must have been discontinued for \> 6 months prior to study entry. * Patients receiving intermittent hormonal therapy for their rising PSA state are considered eligible if testosterone level is above 150ng/dl and treatment was discontinued \> 6 months and agree not to have additional injections while on study drug. * No clinical or radiological evidence of distant metastases (excluding prostascint scan/PET in absence of radiographic disease in Bone scan, CT scan or MRI if used). Lymph node up to 2 cm size is allowed for the study. * ECOG \< 2 or Karnofsky Performance status \>70% within 14 days before being registered for protocol therapy (Appendix B) * Normal organ function with acceptable initial laboratory values: * Absolute neutrophil count ≥ 1 x 109/L * Platelets \> 50 x 109/L * Creatinine \<1.5 mg/dL * Bilirubin \<1.5 X ULN (institutional upper limits of normal) * AST (SGOT) and ALT (SGPT) ≤ 1.5 x ULN * Willingness to use adequate methods of contraception throughout study participation and for at least 3 months after completing therapy Exclusion Criteria: * Metastatic disease or currently active second malignancy * History of Sinus Node Disease and AV Block, Accessory AV Pathway (Wolff-Parkinson-White Syndrome), history of Acute Myocardial Infarction. * Electrolyte imbalance (hypokalemia, hypo- or hypercalcemia, hypomagnesemia) * Severe pulmonary disease and hypoxia * Medical conditions such as uncontrolled hypertension, uncontrolled diabetes mellitus, active infectious hepatitis, type A, B or C, hypothyroidism or hyperthyroidism, which would, in the opinion of the investigator, make this protocol unreasonably hazardous. * Major thoracic or abdominal surgery within the prior 3 weeks. * Patients with GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis). * Use of any prohibited concomitant medications: The washout period is at least 2 weeks before starting the study. * Insufficient time from last prior regimen or radiation exposure: Systemic therapies for prostate cancer within 28 days prior to digoxin; strontium-89 within 12 weeks; bicalutamide within 6 weeks. * Persistent Grade \>2 treatment-related toxicity from prior therapy * History of any digoxin-related or drug induced anaphylactic reaction * Receipt of another investigational agent within 6 months of study entry. Patient must have recovered from all side effects of prior investigational therapy.