PMID- 22772060
OWN - NLM
STAT- MEDLINE
DCOM- 20130228
LR  - 20220601
IS  - 1476-5551 (Electronic)
IS  - 0887-6924 (Linking)
VI  - 27
IP  - 1
DP  - 2013 Jan
TI  - MK-0457, an Aurora kinase and BCR-ABL inhibitor, is active in patients with 
      BCR-ABL T315I leukemia.
PG  - 113-7
LID - 10.1038/leu.2012.186 [doi]
AB  - MK-0457, an Aurora kinase and BCR-ABL inhibitor, was studied on a Phase I/II 
      study in 77 patients with refractory hematologic malignancies. The average number 
      of cycles per patient was 3 (range 1-21). Maximum tolerated doses for a 5-day 
      short infusion and continuous infusion regimens were 40 mg/m(2)/h and 144 
      mg/m(2)/h, respectively. Drug-related adverse events (AEs) included transient 
      mucositis and alopecia. Eight of 18 patients with BCR-ABL T315I-mutated chronic 
      myelogenous leukemia (44%) had hematologic responses and one of three patients 
      (33%) with Philadelphia chromosome-positive acute lymphoblastic leukemia obtained 
      complete remission. MK-0457 has important activity in patients with leukemias 
      expressing the highly resistant T315I BCR-ABL mutation.
FAU - Giles, F J
AU  - Giles FJ
AD  - HRB Clinical Research Facilities, National University of Ireland Galway and 
      Trinity College Dublin, Galway, Ireland. frankgiles@aol.com
FAU - Swords, R T
AU  - Swords RT
FAU - Nagler, A
AU  - Nagler A
FAU - Hochhaus, A
AU  - Hochhaus A
FAU - Ottmann, O G
AU  - Ottmann OG
FAU - Rizzieri, D A
AU  - Rizzieri DA
FAU - Talpaz, M
AU  - Talpaz M
FAU - Clark, J
AU  - Clark J
FAU - Watson, P
AU  - Watson P
FAU - Xiao, A
AU  - Xiao A
FAU - Zhao, B
AU  - Zhao B
FAU - Bergstrom, D
AU  - Bergstrom D
FAU - Le Coutre, P D
AU  - Le Coutre PD
FAU - Freedman, S J
AU  - Freedman SJ
FAU - Cortes, J E
AU  - Cortes JE
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120709
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Piperazines)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 234335M86K (tozasertib)
RN  - EC 2.7.10.2 (Fusion Proteins, bcr-abl)
RN  - EC 2.7.11.1 (Aurora Kinases)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Aurora Kinases
MH  - Drug Resistance, Neoplasm/drug effects/genetics
MH  - Female
MH  - Follow-Up Studies
MH  - Fusion Proteins, bcr-abl/*antagonists & inhibitors
MH  - Humans
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*drug therapy/genetics
MH  - Leukemia, Myeloid, Acute/*drug therapy/genetics
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Mutation/*genetics
MH  - Neoplasm Staging
MH  - Philadelphia Chromosome
MH  - Piperazines/*therapeutic use
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*drug therapy/genetics
MH  - Prognosis
MH  - Protein Kinase Inhibitors/*therapeutic use
MH  - Protein Serine-Threonine Kinases/antagonists & inhibitors
MH  - Remission Induction
MH  - Young Adult
EDAT- 2012/07/10 06:00
MHDA- 2013/03/01 06:00
CRDT- 2012/07/10 06:00
PHST- 2012/07/10 06:00 [entrez]
PHST- 2012/07/10 06:00 [pubmed]
PHST- 2013/03/01 06:00 [medline]
AID - leu2012186 [pii]
AID - 10.1038/leu.2012.186 [doi]
PST - ppublish
SO  - Leukemia. 2013 Jan;27(1):113-7. doi: 10.1038/leu.2012.186. Epub 2012 Jul 9.