Arsenic trioxide and low-dose cytarabine in older patients with untreated acute myeloid leukemia, excluding acute promyelocytic leukemia

BACKGROUND: Acute myeloid leukemia (AML) carries a dismal prognosis in older patients. In this study, the authors evaluated the safety and efficacy of arsenic trioxide combined with low-dose cytarabine in untreated patients aged >or=60 years with AML. METHODS: In a phase 1/2 design, arsenic trioxide was administered intravenously at a dose of 0.25 mg/kg on Days 1 through 5 and on Days 8 through 12, and low-dose cytarabine was given subcutaneously twice daily on Days 1 through 14 in escalating doses to a target of 10 mg/m(2) per dose. Of 64 patients who had pathologically confirmed AML, excluding patients with acute promyelocytic leukemia and using World Health Organization criteria, the median age was 71 years, 10 patients (16%) had treatment-related AML, 40 patients (63%) had an antecedent myelodysplastic syndrome or myeloproliferative disorder, and 35 patients (55%) had unfavorable cytogenetics. Thirty-four patients (53%) had an Eastern Cooperative Oncology Group performance status of 2 or 3. RESULTS: Complete remission was achieved in 21 of 61 patients (34%), including 15 of 50 patients (30%) who had secondary or treatment-related AML, 10 of 33 patients (30%) who had unfavorable cytogenetics, and 6 of 34 patients (18%) who had a poor baseline performance status. The mortality rate within the first 4 weeks was 8%. Neutropenic fever was observed in >80% of patients, and 41% of patients had bacteremia. Nonhematologic toxicity generally was mild and reversible and included fatigue, nausea, diarrhea, rash, peripheral edema, and elevated transaminases. There were no clinically significant cardiac arrhythmias. CONCLUSIONS: The addition of arsenic trioxide to low-dose cytarabine appeared to improve responses in elderly patients who had AML compared with either agent alone, and a randomized trial of the combination versus single-agent low-dose cytarabine is ongoing.