A Phase I study to assess the safety, pharmacokinetics and efficacy of barasertib (AZD1152), an Aurora B kinase inhibitor, in Japanese patients with advanced acute myeloid leukemia

Leuk Res. 2011 Oct;35(10):1384-9. doi: 10.1016/j.leukres.2011.04.008. Epub 2011 May 11.

Abstract

Barasertib (AZD1152) is a highly potent and selective Aurora B kinase inhibitor. The safety, efficacy and pharmacokinetic (PK) profile of barasertib were investigated in Japanese patients with advanced acute myeloid leukemia. Barasertib (50-1200mg) was administered as a continuous 7-day intravenous infusion every 21 days. No dose-limiting toxicities were reported and barasertib 1200mg was chosen for further evaluation in Japanese patients. Neutropenia and febrile neutropenia were the most commonly reported adverse events. The PK profile was similar to Western patients. A promising overall hematologic response rate of 19% was achieved, which warrants further investigation in these patients.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study

MeSH terms

  • Adult
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics*
  • Asians
  • Aurora Kinase B
  • Aurora Kinases
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug-Related Side Effects and Adverse Reactions
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / pharmacokinetics*
  • Female
  • Humans
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / pathology
  • Leukocyte Count
  • Male
  • Middle Aged
  • Neutropenia / pathology
  • Organophosphates / administration & dosage
  • Organophosphates / adverse effects
  • Organophosphates / pharmacokinetics*
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Protein Serine-Threonine Kinases / metabolism
  • Quinazolines / administration & dosage
  • Quinazolines / adverse effects
  • Quinazolines / pharmacokinetics*
  • Treatment Outcome

Substances

  • 2-((3-((4-((5-(2-((3-fluorophenyl)amino)-2-oxoethyl)-1H-pyrazol-3-yl)amino)quinazolin-7-yl)oxy)propyl)(ethyl)amino)ethyl dihydrogen phosphate
  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Organophosphates
  • Quinazolines
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • Protein Serine-Threonine Kinases