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

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

Keywords

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

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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