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

F. J. Giles, Ronan 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 journalArticle

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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 languageEnglish
Pages (from-to)113-117
Number of pages5
JournalLeukemia
Volume27
Issue number1
DOIs
StatePublished - Jan 1 2013

Fingerprint

Aurora Kinases
Leukemia
Philadelphia Chromosome
Mucositis
Maximum Tolerated Dose
Alopecia
Hematologic Neoplasms
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Drug-Related Side Effects and Adverse Reactions
Precursor Cell Lymphoblastic Leukemia-Lymphoma
VX680
Mutation

Keywords

  • aurora kinase
  • chronic myeloid leukemia
  • MK0457
  • T315I mutation

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

Giles, F. J., Swords, R. T., Nagler, A., Hochhaus, A., Ottmann, O. G., Rizzieri, D. A., ... 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

MK-0457, an Aurora kinase and BCR-ABL inhibitor, is active in patients with BCR-ABL T315I leukemia. / Giles, F. J.; Swords, Ronan 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.

In: Leukemia, Vol. 27, No. 1, 01.01.2013, p. 113-117.

Research output: Contribution to journalArticle

Giles, FJ, Swords, RT, Nagler, A, Hochhaus, A, Ottmann, OG, Rizzieri, DA, Talpaz, M, Clark, J, Watson, P, Xiao, A, Zhao, B, Bergstrom, D, Le Coutre, PD, Freedman, SJ & Cortes, JE 2013, 'MK-0457, an Aurora kinase and BCR-ABL inhibitor, is active in patients with BCR-ABL T315I leukemia', Leukemia, vol. 27, no. 1, pp. 113-117. https://doi.org/10.1038/leu.2012.186
Giles FJ, Swords RT, Nagler A, Hochhaus A, Ottmann OG, Rizzieri DA et al. MK-0457, an Aurora kinase and BCR-ABL inhibitor, is active in patients with BCR-ABL T315I leukemia. Leukemia. 2013 Jan 1;27(1):113-117. https://doi.org/10.1038/leu.2012.186
Giles, F. J. ; Swords, Ronan 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. / MK-0457, an Aurora kinase and BCR-ABL inhibitor, is active in patients with BCR-ABL T315I leukemia. In: Leukemia. 2013 ; Vol. 27, No. 1. pp. 113-117.
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