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 journalArticle

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

Keywords

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

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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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