title: Clofarabine Plus Low-Dose Cytarabine Is as Effective as and Less Toxic Than Intensive Chemotherapy in Elderly AML Patients.
abstract: BACKGROUND
  Most patients with acute myeloid leukemia (AML) age ≥ 60 years are not offered intensive induction because of high mortality. Phase 2 studies of clofarabine plus low-dose cytarabine (CLDA) as frontline therapy for elderly AML patients demonstrated high response and acceptable toxicity.
  
  
  METHODS
  We hypothesized that induction therapy with CLDA provides equivalent outcomes to but is less toxic than intensive induction in these patients. To test this hypothesis, we conducted a propensity score-matched comparison of AML patients age ≥ 60 years given induction CLDA versus idarubicin and cytarabine (IA). Ninety-five patients in both groups were matched according to their propensity score.
  
  
  RESULTS
  We did not observe statistically significant differences in response, overall survival, or mortality rate between the two induction regimens. However, CLDA produced significantly fewer grade 3 or worse toxicities (46% for CLDA vs. 62% for IA; P = .03). Furthermore, among responders, the median response duration was significantly longer with CLDA when we censored patients who underwent stem cell transplantation (15.9 months for CLDA vs. 7.0 months for IA; P = .033).
  
  
  CONCLUSIONS
  Compared with intensive induction, CLDA offers equivalent responses and survival but less toxicity in clinically well-matched cohorts of elderly AML patients. Prospective randomized trials to confirm these findings are warranted.
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Tapan
authors.initials: T
authors.lastname: Kadia
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Courtney
authors.initials: C
authors.lastname: DiNardo
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Sherry
authors.initials: S
authors.lastname: Pierce
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Zeev
authors.initials: Z
authors.lastname: Estrov
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Marina
authors.initials: M
authors.lastname: Konopleva
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Michael
authors.initials: M
authors.lastname: Andreeff
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address: jcortes@mdanderson.org.
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
mesh_terms: D000227:Adenine Nucleotides / Q000008:administration & dosage; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001087:Arabinonucleosides / Q000008:administration & dosage; D000077866:Clofarabine; D015331:Cohort Studies; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D019233:Retreatment; D016896:Treatment Outcome
chemical_list: D000227:Adenine Nucleotides; D001087:Arabinonucleosides; D003561:Cytarabine; D000077866:Clofarabine
keywords: Acute myeloid leukemia; Clofarabine; Induction therapy; Intensive chemotherapy; Propensity matching