MK-0457, an Aurora kinase and BCR-ABL inhibitor, is active in patients with BCR-ABL T315I leukemia

F. J. Giles; R. T. Swords; A. Nagler; A. Hochhaus; O. G. Ottmann; D. A. Rizzieri; M. Talpaz; J. Clark; P. Watson; A. Xiao; B. Zhao; D. Bergstrom; P. D. Le Coutre; S. J. Freedman; J. E. Cortes

doi:10.1038/leu.2012.186

MK-0457, an Aurora kinase and BCR-ABL inhibitor, is active in patients with BCR-ABL T315I leukemia

F. J. Giles^*, R. T. Swords, A. Nagler, A. Hochhaus, O. G. Ottmann, D. A. Rizzieri, M. Talpaz, J. Clark, P. Watson, A. Xiao, B. Zhao, D. Bergstrom, P. D. Le Coutre, S. J. Freedman, J. E. Cortes

^*Corresponding author for this work

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

59 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	113-117
Number of pages	5
Journal	Leukemia
Volume	27
Issue number	1
DOIs	https://doi.org/10.1038/leu.2012.186
State	Published - Jan 2013

Keywords

MK0457
T315I mutation
aurora kinase
chronic myeloid leukemia

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/leu.2012.186

Cite this

Giles, F. J., Swords, R. T., Nagler, A., Hochhaus, A., Ottmann, O. G., Rizzieri, D. A., Talpaz, M., Clark, J., Watson, P., Xiao, A., Zhao, B., Bergstrom, D., Le Coutre, P. D., Freedman, S. J., & Cortes, J. E. (2013). MK-0457, an Aurora kinase and BCR-ABL inhibitor, is active in patients with BCR-ABL T315I leukemia. Leukemia, 27(1), 113-117. https://doi.org/10.1038/leu.2012.186

@article{3bab175f709a4d8e9ff529b0cd850b2a,

title = "MK-0457, an Aurora kinase and BCR-ABL inhibitor, is active in patients with BCR-ABL T315I leukemia",

abstract = "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.",

keywords = "MK0457, T315I mutation, aurora kinase, chronic myeloid leukemia",

author = "Giles, {F. J.} and Swords, {R. T.} and A. Nagler and A. Hochhaus and Ottmann, {O. G.} and Rizzieri, {D. A.} and M. Talpaz and J. Clark and P. Watson and A. Xiao and B. Zhao and D. Bergstrom and {Le Coutre}, {P. D.} and Freedman, {S. J.} and Cortes, {J. E.}",

note = "Funding Information: We acknowledge the study coordinators, nurses and physicians who contributed to this study, and the patients and their families for their participation. We thank Boyd Scott for editorial assistance. The research of Francis Giles, Arnon Nagler, Andreas Hochhaus, Oliver G Ottmann, David Rizzieri, Moshe Talpaz, Philipp Le Coutre and Jorge Cortes was funded by Merck.",

year = "2013",

month = jan,

doi = "10.1038/leu.2012.186",

language = "English (US)",

volume = "27",

pages = "113--117",

journal = "Leukemia",

issn = "0887-6924",

publisher = "Springer Nature",

number = "1",

}

TY - JOUR

T1 - MK-0457, an Aurora kinase and BCR-ABL inhibitor, is active in patients with BCR-ABL T315I leukemia

AU - Giles, F. J.

AU - Swords, R. T.

AU - Nagler, A.

AU - Hochhaus, A.

AU - Ottmann, O. G.

AU - Rizzieri, D. A.

AU - Talpaz, M.

AU - Clark, J.

AU - Watson, P.

AU - Xiao, A.

AU - Zhao, B.

AU - Bergstrom, D.

AU - Le Coutre, P. D.

AU - Freedman, S. J.

AU - Cortes, J. E.

N1 - Funding Information: We acknowledge the study coordinators, nurses and physicians who contributed to this study, and the patients and their families for their participation. We thank Boyd Scott for editorial assistance. The research of Francis Giles, Arnon Nagler, Andreas Hochhaus, Oliver G Ottmann, David Rizzieri, Moshe Talpaz, Philipp Le Coutre and Jorge Cortes was funded by Merck.

PY - 2013/1

Y1 - 2013/1

N2 - 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.

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.

KW - MK0457

KW - T315I mutation

KW - aurora kinase

KW - chronic myeloid leukemia

UR - http://www.scopus.com/inward/record.url?scp=84873570889&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84873570889&partnerID=8YFLogxK

U2 - 10.1038/leu.2012.186

DO - 10.1038/leu.2012.186

M3 - Article

C2 - 22772060

AN - SCOPUS:84873570889

SN - 0887-6924

VL - 27

SP - 113

EP - 117

JO - Leukemia

JF - Leukemia

IS - 1

ER -

MK-0457, an Aurora kinase and BCR-ABL inhibitor, is active in patients with BCR-ABL T315I leukemia

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this