title: Phase 1 study of arsenic trioxide, high-dose cytarabine, and idarubicin to down-regulate constitutive signal transducer and activator of transcription 3 activity in patients aged <60 years with acute myeloid leukemia.
abstract: BACKGROUND
  Constitutive activation of signal transducer and activator of transcription-3 (STAT3) was detected in blasts from approximately 50% of patients with acute myeloid leukemia (AML) and was correlated with an adverse outcome. In vitro treatment of AML blasts with arsenic trioxide (ATO) down-regulated STAT3 activity within 6 hours associated with a reduced viability within 48 hours.
  
  
  METHODS
  A phase 1 clinical trial to evaluate the biologically effective dose and/or the maximally tolerated dose (MTD) of ATO in vivo in conjunction with high-dose cytarabine (Hidac) and idarubicin (Ida) in patients with AML aged <60 years was conducted. Data were compared with 117 historic AML patients who had received treatment with Hidac/Ida.
  
  
  RESULTS
  In total, 61 patients were enrolled onto 11 different dose levels (from 0.01 to 0.65 mg/kg ideal body weight). The MTD was 0.5 mg/kg. Compared with historic controls, patients who received ATO/Hidac/Ida, although they had similar pretreatment characteristics, had better overall survival (P = .039).
  
  
  CONCLUSIONS
  ATO priming may have improved the outcome of patients aged <60 years with AML who received Hidac/Ida. The current data suggested that ATO may enhance the effect of chemotherapy. The authors concluded that further studies of this novel combination are warranted.
authors: Leukemia Section, Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. meir.wetzler@roswellpark.org
authors: Meir
authors: M
authors: Wetzler
authors: Chris
authors: C
authors: Andrews
authors: Laurie A
authors: LA
authors: Ford
authors: Sheila
authors: S
authors: Tighe
authors: Maurice
authors: M
authors: Barcos
authors: Sheila N J
authors: SN
authors: Sait
authors: Annemarie W
authors: AW
authors: Block
authors: Norma J
authors: NJ
authors: Nowak
authors: Maria R
authors: MR
authors: Baer
authors: Eunice S
authors: ES
authors: Wang
authors: Heinz
authors: H
authors: Baumann
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage* / Q000009:adverse effects; D003561:Cytarabine / Q000008:administration & dosage* / Q000009:adverse effects; D015536:Down-Regulation; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage* / Q000009:adverse effects; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010087:Oxides / Q000008:administration & dosage* / Q000009:adverse effects; D050796:STAT3 Transcription Factor / Q000378:metabolism*
chemical_list: D001152:Arsenicals; D010087:Oxides; D050796:STAT3 Transcription Factor; D003561:Cytarabine; D000077237:Arsenic Trioxide; D015255:Idarubicin