title: Sorafenib in combination with intensive chemotherapy in elderly patients with acute myeloid leukemia: results from a randomized, placebo-controlled trial.
abstract: OBJECTIVE
  The prognosis of elderly patients with acute myeloid leukemia (AML) is still dismal even with intensive chemotherapy. In this trial, we compared the antileukemic activity of standard induction and consolidation therapy with or without the addition of the kinase inhibitor sorafenib in elderly patients with AML.
  
  
  METHODS
  All patients received standard cytarabine and daunorubicin induction (7+3 regimen) and up to two cycles of intermediate-dose cytarabine consolidation. Two hundred one patients were equally randomly assigned to receive either sorafenib or placebo between the chemotherapy cycles and subsequently for up to 1 year after the beginning of therapy. The primary objective was to test for an improvement in event-free survival (EFS). Overall survival (OS), complete remission (CR) rate, tolerability, and several predefined subgroup analyses were among the secondary objectives.
  
  
  RESULTS
  Age, sex, CR and early death (ED) probability, and prognostic factors were balanced between both study arms. Treatment in the sorafenib arm did not result in significant improvement in EFS or OS. This was also true for subgroup analyses, including the subgroup positive for FLT3 internal tandem duplications. Results of induction therapy were worse in the sorafenib arm, with higher treatment-related mortality and lower CR rates. More adverse effects occurred during induction therapy in the sorafenib arm, and patients in this arm received less consolidation chemotherapy as a result of higher induction toxicity.
  
  
  CONCLUSIONS
  In conclusion, combination of standard induction and consolidation therapy with sorafenib in the schedule investigated in our trial is not beneficial for elderly patients with AML.
authors.affiliation: Department of Medicine, Hematology/Oncology, Geother-University, Frankfurt, Germany. hubert.serve@kgu.de
authors.forename: Hubert
authors.initials: H
authors.lastname: Serve
authors.forename: Utz
authors.initials: U
authors.lastname: Krug
authors.forename: Ruth
authors.initials: R
authors.lastname: Wagner
authors.forename: M Cristina
authors.initials: MC
authors.lastname: Sauerland
authors.forename: Achim
authors.initials: A
authors.lastname: Heinecke
authors.forename: Uta
authors.initials: U
authors.lastname: Brunnberg
authors.forename: Markus
authors.initials: M
authors.lastname: Schaich
authors.forename: Oliver
authors.initials: O
authors.lastname: Ottmann
authors.forename: Justus
authors.initials: J
authors.lastname: Duyster
authors.forename: Hannes
authors.initials: H
authors.lastname: Wandt
authors.forename: Thomas
authors.initials: T
authors.lastname: Fischer
authors.forename: Aristoteles
authors.initials: A
authors.lastname: Giagounidis
authors.forename: Andreas
authors.initials: A
authors.lastname: Neubauer
authors.forename: Albrecht
authors.initials: A
authors.lastname: Reichle
authors.forename: Walter
authors.initials: W
authors.lastname: Aulitzky
authors.forename: Richard
authors.initials: R
authors.lastname: Noppeney
authors.forename: Igor
authors.initials: I
authors.lastname: Blau
authors.forename: Volker
authors.initials: V
authors.lastname: Kunzmann
authors.forename: Reingard
authors.initials: R
authors.lastname: Stuhlmann
authors.forename: Alwin
authors.initials: A
authors.lastname: Krämer
authors.forename: Karl-Anton
authors.initials: KA
authors.lastname: Kreuzer
authors.forename: Christian
authors.initials: C
authors.lastname: Brandts
authors.forename: Björn
authors.initials: B
authors.lastname: Steffen
authors.forename: Christian
authors.initials: C
authors.lastname: Thiede
authors.forename: Carsten
authors.initials: C
authors.lastname: Müller-Tidow
authors.forename: Gerhard
authors.initials: G
authors.lastname: Ehninger
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Berdel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010671:Phenylurea Compounds / Q000008:administration & dosage*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D000077157:Sorafenib; D051941:fms-Like Tyrosine Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics
chemical_list: D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000077157:Sorafenib; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3