title: Arsenic trioxide and low-dose cytarabine in older patients with untreated acute myeloid leukemia, excluding acute promyelocytic leukemia.
abstract: BACKGROUND
  Acute myeloid leukemia (AML) carries a dismal prognosis in older patients. In this study, the authors evaluated the safety and efficacy of arsenic trioxide combined with low-dose cytarabine in untreated patients aged >or=60 years with AML.
  
  
  METHODS
  In a phase 1/2 design, arsenic trioxide was administered intravenously at a dose of 0.25 mg/kg on Days 1 through 5 and on Days 8 through 12, and low-dose cytarabine was given subcutaneously twice daily on Days 1 through 14 in escalating doses to a target of 10 mg/m(2) per dose. Of 64 patients who had pathologically confirmed AML, excluding patients with acute promyelocytic leukemia and using World Health Organization criteria, the median age was 71 years, 10 patients (16%) had treatment-related AML, 40 patients (63%) had an antecedent myelodysplastic syndrome or myeloproliferative disorder, and 35 patients (55%) had unfavorable cytogenetics. Thirty-four patients (53%) had an Eastern Cooperative Oncology Group performance status of 2 or 3.
  
  
  RESULTS
  Complete remission was achieved in 21 of 61 patients (34%), including 15 of 50 patients (30%) who had secondary or treatment-related AML, 10 of 33 patients (30%) who had unfavorable cytogenetics, and 6 of 34 patients (18%) who had a poor baseline performance status. The mortality rate within the first 4 weeks was 8%. Neutropenic fever was observed in >80% of patients, and 41% of patients had bacteremia. Nonhematologic toxicity generally was mild and reversible and included fatigue, nausea, diarrhea, rash, peripheral edema, and elevated transaminases. There were no clinically significant cardiac arrhythmias.
  
  
  CONCLUSIONS
  The addition of arsenic trioxide to low-dose cytarabine appeared to improve responses in elderly patients who had AML compared with either agent alone, and a randomized trial of the combination versus single-agent low-dose cytarabine is ongoing.
authors.affiliation: Leukemia Program, Weill Medical College of Cornell University and New York Presbyterian Hospital, New York, New York 10021, USA. gar2001@med.cornell.edu
authors.forename: Gail J
authors.initials: GJ
authors.lastname: Roboz
authors.forename: Ellen K
authors.initials: EK
authors.lastname: Ritchie
authors.forename: Tania
authors.initials: T
authors.lastname: Curcio
authors.forename: Juliette
authors.initials: J
authors.lastname: Provenzano
authors.forename: Rebecca
authors.initials: R
authors.lastname: Carlin
authors.forename: Michael
authors.initials: M
authors.lastname: Samuel
authors.forename: Beth
authors.initials: B
authors.lastname: Wittenberg
authors.forename: Madhu
authors.initials: M
authors.lastname: Mazumdar
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Christos
authors.forename: Susan
authors.initials: S
authors.lastname: Mathew
authors.forename: Sandra
authors.initials: S
authors.lastname: Allen-Bard
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Feldman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D015473:Leukemia, Promyelocytic, Acute; D008297:Male; D008875:Middle Aged; D010087:Oxides / Q000008:administration & dosage; D011379:Prognosis; D012074:Remission Induction; D015996:Survival Rate
chemical_list: D001152:Arsenicals; D010087:Oxides; D003561:Cytarabine; D000077237:Arsenic Trioxide