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Clin Lymphoma Myeloma Leuk. 2014 Oct;14(5):395-400.e1. doi: 10.1016/j.clml.2014.01.009. Epub 2014 Feb 3.

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

Author information

1
Department of Investigational Cancer Therapeutics, Phase I Clinical Trials Program, The University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address: atsimber@mdanderson.org.
2
Division of Cancer Medicine, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
3
Division of Hematology, University of Washington School of Medicine, Seattle, WA.
4
Gilead Sciences, Foster City, CA.
5
Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX.

Abstract

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/m(2)/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 ≥ 3 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.

KEYWORDS:

DLT; High-risk MDS; Poor-risk; Response; Toxicity

PMID:
24637132
PMCID:
PMC4387892
DOI:
10.1016/j.clml.2014.01.009
[Indexed for MEDLINE]
Free PMC Article
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