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

20021 Background: Recent studies indicate that cardiac glycosides have anti-neoplastic activities. Digoxin prevents the growth of mammary tumors in susceptible mice. Several cell lines are sensitive to cardiac glycosides including breast cancer (MCF-7), renal adenocarcinoma (TK -10), melanoma (UACC-62), leukemia (K-562), HeLa, prostate cancer and NSCLC. The mechanism of action is complex in nature and evolving. Consequently, the addition of digoxin may augment the cytotoxic effects of bio-chemotherapy against melanoma.,Forty-seven patients with stage IV melanoma without CNS metastasis with a median age of 52 years (25-73), 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/m on day 1; cisplatin, IV, 20 mg/m on days 1-4; vinblastine, IV, 1.2 mg/m on days 1-4; IL-2, IV over 24 hours, 9 M IU/m on days 1-4; interferon, SC, 5 MU/m 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. Common toxicities include hypotension, neutropenia, thrombocytopenia, nausea, vomiting, and renal insufficiency. Re-admission rate was less than 5%. Approximately 35% of patients required 25% dose reduction due to toxicities.,Ten patients achieved CR (21.3%), 16 patients had a PR (34%), and 7 patients had a SD (14.9%). The overall clinical benefit was 70%. Fourteen patients (29.8%) experienced PD and were taken off the protocol. Seventeen patients are alive. At 18 months, 3 living patients have NED. Twenty-nine patients have died due to progression of melanoma. MOS is 8 months (1-25).,Addition of digoxin to bio-chemotherapy may have a synergistic anti-tumor effect on patients with melanoma. Accrual to this clinical trial is on-going and final overall survival and progression free survival will be presented in future. No significant financial relationships to disclose.