BACKGROUND:
High-dose cytarabine (HDAC) and etoposide, two of the most active drugs in relapsed acute myeloid leukemia (AML), have shown synergistic activity with platinum analogues in both preclinical and clinical studies. The present study was undertaken to assess the efficacy and toxicity of a combination regimen of HDAC, etoposide and cisplatin (HAEP) in adult patients with relapsed AML.
METHODS:
Between 1990 and 1998, 16 patients with relapsed AML were treated with HAEP salvage therapy, which consisted of HDAC (2.0g/m2, q12hr x2/d), etoposide (100mg/m2/d) and cisplatin (20mg/m2/d, 2-hr infusion) for 5 days.
RESULTS:
Ten of 16 patients (62.5%) achieved a complete remission (CR). Six patients who could not attain CR died either of infection (5 patients) or CNS hemorrhage (1 patient). The median overall survival (OS) for all patients was 63 (range, 6~253) weeks. Median disease free survival (DFS) for those who achieved CR was 57 weeks. At the time of analysis, 6 patients were alive with a median follow-up of 68 (range, 22~152) months. All patients experienced fever in the setting of grade IV neutropenia. The median length of neutropenia and thrombocytopenia was 36 and 41 days, respectively. The median period of neutropenic fever in complete responders was 20 days. The main non-hematologic grade III~IV toxicities were mucositis(25%) and hepatic dysfunction (40%).
CONCLUSIONS:
The HAEP salvage regimen appears highly effective in obtaining high CR rate and possibly long-term survival in relapsed AML. The results suggest that the addition of cisplatin may enhance the activity of HDAC and etoposide. Hematologic toxicity was high, but there was no excessive or cumulative non-hematologic toxicity. Further evaluation of this novel combination in AML is indicated.

Keywords: Acute myeloid leukemia, Salvage therapy, High-dose cytarabine, Etoposide, Cisplatin