A phase i study of fludarabine, cytarabine, and oxaliplatin therapy in patients with relapsed or refractory acute myeloid leukemia

We conducted a phase I study combining oxaliplatin with cytarabine and fludarabine for patients with relapsed or refractory AML. Oxaliplatin 30 mg/m2/d on days 1 to 4, fludarabine 30 mg/m2, and cytarabine 500 mg/ m² on days 2 to 6 was the MTD. Of 27 patients who were treated, 3 had a complete remission and 2 patients had complete remission without platelet recovery.

Purpose: The combination of cytarabine and fludarabine was associated with superior clinical outcomes compared with those of high-dose cytarabine in relapse acute myeloid leukemia (AML). We conducted a phase I study combining oxaliplatin with cytarabine and fludarabine therapy for patients with relapsed or refractory AML.

Patients and Methods: Between January 2008 and November 2009, 27 patients were registered in the study. Patients had histologically confirmed disease, performance status 0 to 2, and adequate organ function. The treatment regimen consisted of increasing doses of oxaliplatin (25, 30, or 35 mg/ m2/d) on days 1 to 4 (escalation phase), and fludarabine (30 mg/m2) and cytarabine (500 mg/m2) on days 2 to 6, every 28 days for ≤ 6 cycles. The dose-limiting toxicity was defined as any symptomatic grade ≥ nonhematologic toxicity lasting ≥3 days and involving a major organ system.

Results: Of 27 patients, 12 were treated in the dose-escalation phase and 15 at the maximum tolerated dose for oxaliplatin (30 mg/m2; expansion phase). All patients were evaluable for toxicity and response. Only 1 patient received the second cycle; the remaining patients received no further study treatment, owing to slow recovery from toxicities 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). In all, 3 patients had a complete remission and 2 patients complete response without platelet recovery.

Conclusion: Oxaliplatin, cytarabine, and fludarabine therapy had antileukemic activity in patients with poor-risk AML, but it was associated with toxicity. Different schedules and doses may be better tolerated.