title: Final results of a phase 2 trial of clofarabine and low-dose cytarabine alternating with decitabine in older patients with newly diagnosed acute myeloid leukemia.
abstract: BACKGROUND
  The treatment of older adults with acute myeloid leukemia (AML) using standard intensive chemotherapy has been associated with poor outcomes. Effective, less toxic therapies are needed to achieve and maintain durable remissions.
  
  
  METHODS
  One hundred eighteen patients with newly diagnosed AML (median age, 68 years; range, 60-81 years) were treated with a regimen of clofarabine and low-dose cytarabine (LDAC) alternating with decitabine (DAC). The induction consisted of intravenous clofarabine at 20 mg/m(2) on days 1 to 5 combined with subcutaneous LDAC at 20 mg twice daily on days 1 to 10. Responding patients were then treated with a prolonged consolidation/maintenance regimen consisting of cycles of clofarabine plus LDAC alternating with cycles of DAC.
  
  
  RESULTS
  The overall response rate was 68%. The complete remission (CR) rate was 60% overall, 71% for patients with a diploid karyotype, and 50% for patients with an adverse karyotype. The median overall survival (OS) was 11.1 months for all patients and 18.5 months for those achieving a CR/complete remission with incomplete platelet recovery (CRp). The median relapse-free survival for patients achieving a CR/CRp was 14.1 months. According to a multivariate analysis, only adverse cytogenetics and a white blood cell count ≥ 10 × 10(9)/L predicted worse OS. The regimen was well tolerated with 4- and 8-week mortality rates of 3% and 7%, respectively. The most common nonhematologic adverse events were nausea, elevated liver enzymes, and rash.
  
  
  CONCLUSIONS
  The lower intensity, prolonged-therapy program of clofarabine and LDAC alternating with DAC is well tolerated and highly effective in older patients with AML.
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Tapan M
authors: TM
authors: Kadia
authors: Division of Leukemia, John Theurer Cancer Center, Hackensack, New Jersey.
authors: Stefan
authors: S
authors: Faderl
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Farhad
authors: F
authors: Ravandi
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Elias
authors: E
authors: Jabbour
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Guillermo
authors: G
authors: Garcia-Manero
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Gautam
authors: G
authors: Borthakur
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Alessandra
authors: A
authors: Ferrajoli
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Marina
authors: M
authors: Konopleva
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Jan
authors: J
authors: Burger
authors: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Xuelin
authors: X
authors: Huang
authors: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Xuemei
authors: X
authors: Wang
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Sherry
authors: S
authors: Pierce
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Mark
authors: M
authors: Brandt
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Jennie
authors: J
authors: Feliu
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Jorge
authors: J
authors: Cortes
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Hagop
authors: H
authors: Kantarjian
mesh_terms: D000227:Adenine Nucleotides / Q000008:administration & dosage; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001087:Arabinonucleosides / Q000008:administration & dosage; D001374:Azacitidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077866:Clofarabine; D003561:Cytarabine / Q000008:administration & dosage; D000077209:Decitabine; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D000227:Adenine Nucleotides; D001087:Arabinonucleosides; D003561:Cytarabine; D000077866:Clofarabine; D000077209:Decitabine; D001374:Azacitidine
keywords: elderly acute myeloid leukemia (AML); low intensity; maintenance