A phase II trial of biochemotherapy with cisplatin, vinblastine, dacarbazine, interleukin-2, interferon, and digoxin in melanoma matients

Abstract

8573 Background: Patients with stage IV metastatic melanoma have limited treatment options. Epidemiological studies have demonstrated that there is a lower death rate from breast cancer in patients who are on digoxin therapy (6%) when compared with patients who are not on digoxin therapy (34%). Recent in vitro studies have shown that digoxin inhibits growth and causes apoptosis in multiple cell lines including breast cancer cells (MCF-7), non-small cell lung cancer cells, HeLa cells, renal adenocarcinoma cells (TK-10), neuroblastoma cells, and prostate cancer cells. In addition digoxin enhances the efficacy of chemotherapy against melanoma cells in vitro. Consequently, the addition of digoxin may augment the cytotoxic effects of bio-chemotherapy against stage IV melanoma. Methods: Twenty-seven patients with stage IV melanoma without CNS metastasis with a median age of 51 years (25–69), were enrolled in this open label phase II clinical trial. ECOG performance status was 0 to 1. Patients had normal cardiac, pulmonary, renal and liver function tests. Patients received digoxin 0.25 mg daily throughout all cycles. Patients were hospitalized in ICU for 5 days to receive the therapy and supportive care. Treatment schedule: dacarbazine, IV, 800 mg/m2 on day 1; cisplatin, IV, 20 mg/m2 on days 1–4; vinblastine, IV, 1.2 mg/m2 on days 1–4; IL-2, IV over 24 hours, 9 M IU/m2 on days 1–4; interferon, SC, 5 MU/m2 on days 1–5. After completing 2 cycles (28 days per cycle) patients were evaluated for response by CT and/or FDG-PET imaging studies. Patients who experienced a SD, PR, or CR then completed 2 more cycles of this therapy. There was no treatment related mortality. Results: Seven patients achieved CR (25.9%), five patients had a PR (18.5%), and six patients had a SD (22.2%). The overall clinical benefit was 66.6%. Nine patients (33.3%) experienced progressive disease and were taken off the protocol. Eleven patients (40%) are alive and sixteen patients (60%) have died. Conclusions: Our preliminary data demonstrate that the addition of digoxin to bio-chemotherapy may have a synergistic effect on patients with melanoma. Accrual to this trial is on-going and final overall survival and progression free survival will be evaluated in the future. No significant financial relationships to disclose.