A Phase I Study of Fludarabine, Cytarabine, and Oxaliplatin in Patients with Relapsed or Refractory Acute Myeloid Leukemia

Purpose— The combination of cytarabine and fludarabine was associated with superior clinical outcomes compared to high-dose cytarabine in relapse acute myeloid leukemia (AML). We conducted a phase I study combining oxaliplatin with cytarabine and fludarabine for patients with relapsed or refractory AML. Patients and Methods— Patients had histologically confirmed disease, performance status 0-2 and adequate organ function. The regimen consisted of increasing doses of oxaliplatin (25, 30, or 35 mg/m 2 /d) on days 1-4 (escalation phase) and fludarabine (30 mg/m 2 ) and cytarabine (500 mg/m 2 ) on days 2-6, every 28 days for up to 6 cycles. The dose-limiting toxicity (DLT) was defined as any symptomatic grade ≥3 non-hematological toxicity lasting ≥ 3 days and involving a major organ system. Results— Twenty-seven patients were registered between January 2008 and November 2009. Twelve patients were treated in the dose escalation phase and 15 at the maximum tolerated dose (MTD) for oxaliplatin (30 mg/m 2 ; expansion phase). All patients were evaluable for toxicity and response. Only one of 27 patients received the second cycle; the remaining patients received no further study treatment owing to slow recovery from toxicities and/or physician decision. Grade 3-4 drug-related toxicities included diarrhea (grade 4) and elevated levels of bilirubin (grade 3) and aspartate transaminase (grade 3). Three patients had a complete remission and 2 patients CR without platelet recovery. Conclusion— Oxaliplatin, cytarabine, and fludarabine had antileukemic activity in patients with poor-risk AML, but it was associated with toxicity. Different schedules and doses may be better tolerated.