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

Trinity College Dublin
University of Miami
Sheba Medical Center at Tel Hashomer
Friedrich Schiller University Jena
Goethe University Frankfurt
Duke University
University of Michigan, Ann Arbor
Merck
Charité – Universitätsmedizin Berlin
University of Texas MD Anderson Cancer Center

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

64 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
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
Externally published	Yes

Funding

Funders	Funder number
National Cancer Institute	P30CA016672
Merck

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

MK0457
T315I mutation
aurora kinase
chronic myeloid leukemia

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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

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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",

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doi = "10.1038/leu.2012.186",

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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.

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

Abstract

Funding

UN SDGs

Keywords

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