title: A phase I study of fludarabine, cytarabine, and oxaliplatin therapy in patients with relapsed or refractory acute myeloid leukemia.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Apostolia Maria
authors.initials: AM
authors.lastname: Tsimberidou
authors.affiliation: Division of Cancer Medicine, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Keating
authors.affiliation: Division of Cancer Medicine, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Elias J
authors.initials: EJ
authors.lastname: Jabbour
authors.affiliation: Division of Cancer Medicine, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi-Kashani
authors.affiliation: Division of Cancer Medicine, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.affiliation: Division of Hematology, University of Washington School of Medicine, Seattle, WA.
authors.forename: Elihu
authors.initials: E
authors.lastname: Estey
authors.affiliation: Gilead Sciences, Foster City, CA.
authors.forename: Neby
authors.initials: N
authors.lastname: Bekele
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: William K
authors.initials: WK
authors.lastname: Plunkett
authors.affiliation: Division of Cancer Medicine, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.affiliation: Division of Cancer Medicine, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D006932:Hyperbilirubinemia / Q000139:chemically induced; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D012074:Remission Induction; D016879:Salvage Therapy / Q000009:adverse effects; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D055815:Young Adult
chemical_list: D009944:Organoplatinum Compounds; D003561:Cytarabine; D000077150:Oxaliplatin; D014740:Vidarabine; C024352:fludarabine
keywords: DLT; High-risk MDS; Poor-risk; Response; Toxicity