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

Research output: Contribution to a Journal (Peer & Non Peer) › Article › peer-review

64 Citations (Scopus)

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
Publication status	Published - Jan 2013
Externally published	Yes

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

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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.\}",

year = "2013",

month = jan,

doi = "10.1038/leu.2012.186",

language = "English",

volume = "27",

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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.

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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

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DO - 10.1038/leu.2012.186

M3 - Article

SN - 0887-6924

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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

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Keywords

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