PMID- 23897964
OWN - NLM
STAT- MEDLINE
DCOM- 20131029
LR  - 20220321
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 31
IP  - 25
DP  - 2013 Sep 1
TI  - Sorafenib in combination with intensive chemotherapy in elderly patients with 
      acute myeloid leukemia: results from a randomized, placebo-controlled trial.
PG  - 3110-8
LID - 10.1200/JCO.2012.46.4990 [doi]
AB  - PURPOSE: 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. PATIENTS AND 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. CONCLUSION: 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.
FAU - Serve, Hubert
AU  - Serve H
AD  - Department of Medicine, Hematology/Oncology, Geother-University, Frankfurt, 
      Germany. hubert.serve@kgu.de
FAU - Krug, Utz
AU  - Krug U
FAU - Wagner, Ruth
AU  - Wagner R
FAU - Sauerland, M Cristina
AU  - Sauerland MC
FAU - Heinecke, Achim
AU  - Heinecke A
FAU - Brunnberg, Uta
AU  - Brunnberg U
FAU - Schaich, Markus
AU  - Schaich M
FAU - Ottmann, Oliver
AU  - Ottmann O
FAU - Duyster, Justus
AU  - Duyster J
FAU - Wandt, Hannes
AU  - Wandt H
FAU - Fischer, Thomas
AU  - Fischer T
FAU - Giagounidis, Aristoteles
AU  - Giagounidis A
FAU - Neubauer, Andreas
AU  - Neubauer A
FAU - Reichle, Albrecht
AU  - Reichle A
FAU - Aulitzky, Walter
AU  - Aulitzky W
FAU - Noppeney, Richard
AU  - Noppeney R
FAU - Blau, Igor
AU  - Blau I
FAU - Kunzmann, Volker
AU  - Kunzmann V
FAU - Stuhlmann, Reingard
AU  - Stuhlmann R
FAU - Kramer, Alwin
AU  - Kramer A
FAU - Kreuzer, Karl-Anton
AU  - Kreuzer KA
FAU - Brandts, Christian
AU  - Brandts C
FAU - Steffen, Bjorn
AU  - Steffen B
FAU - Thiede, Christian
AU  - Thiede C
FAU - Muller-Tidow, Carsten
AU  - Muller-Tidow C
FAU - Ehninger, Gerhard
AU  - Ehninger G
FAU - Berdel, Wolfgang E
AU  - Berdel WE
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20130729
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Phenylurea Compounds)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 25X51I8RD4 (Niacinamide)
RN  - 9ZOQ3TZI87 (Sorafenib)
RN  - EC 2.7.10.1 (FLT3 protein, human)
RN  - EC 2.7.10.1 (fms-Like Tyrosine Kinase 3)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Leukemia, Myeloid, Acute/*drug therapy/genetics/mortality
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Niacinamide/administration & dosage/*analogs & derivatives
MH  - Phenylurea Compounds/*administration & dosage
MH  - Protein Kinase Inhibitors/*administration & dosage
MH  - Sorafenib
MH  - fms-Like Tyrosine Kinase 3/antagonists & inhibitors/genetics
EDAT- 2013/07/31 06:00
MHDA- 2013/10/30 06:00
CRDT- 2013/07/31 06:00
PHST- 2013/07/31 06:00 [entrez]
PHST- 2013/07/31 06:00 [pubmed]
PHST- 2013/10/30 06:00 [medline]
AID - JCO.2012.46.4990 [pii]
AID - 10.1200/JCO.2012.46.4990 [doi]
PST - ppublish
SO  - J Clin Oncol. 2013 Sep 1;31(25):3110-8. doi: 10.1200/JCO.2012.46.4990. Epub 2013 
      Jul 29.