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Bosutinib : a review of preclinical and clinical studies in chronic myelogenous leukemia.

AbstractINTRODUCTION:
Chronic myeloid leukemia (CML) is a hematopoietic stem cell disease. It is characterized by a Bcr-Abl (breakpoint cluster region-Abelson leukemia virus) tyrosine kinase fusion protein produced from the Philadelphia (Ph) chromosome. The tyrosine kinase inhibitor (TKI) imatinib was the first targeted therapy licensed for patients with chronic-phase CML. In recent years, many other TKIs have been approved for the treatment of patients with CML. For this reason, the choice of the best strategy treatment has become increasingly complex.
AREAS COVERED:
Bosutinib , a dual Src/Abl kinase inhibitor, has shown potent activity against CML and it has been approved by the US FDA for the treatment of chronic, accelerated or blast-phase Ph+ CML. This review was conducted to describe the preclinical and clinical activity of bosutinib and the safety and tolerability of the drug in the treatment of CML. Included studies were identified through a search of electronic databases in July 2013 and relevant conference proceedings.
EXPERT OPINION:
Imatinib continues to represent the treatment of choice for CML. However, some patients develop resistance or intolerance to imatinib or to other second-generation TKIs. Bosutinib shows a good therapeutic activity with a benign safety profile, no cardiovascular toxicity, and offers an important therapeutic addition to the armamentarium that physicians can use against resistant CML.
AuthorsFrancesca Rusconi, Rocco Piazza, Elisabetta Vagge, Carlo Gambacorti-Passerini
JournalExpert opinion on pharmacotherapy (Expert Opin Pharmacother) Vol. 15 Issue 5 Pg. 701-10 (Apr 2014) ISSN: 1744-7666 [Electronic] England
PMID24479382 (Publication Type: Journal Article, Review)
Chemical References
  • Aniline Compounds
  • Antineoplastic Agents
  • Benzamides
  • Nitriles
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Quinolines
  • bosutinib
  • Imatinib Mesylate
  • Protein-Tyrosine Kinases
  • Fusion Proteins, bcr-abl
Topics
  • Aniline Compounds (pharmacokinetics, therapeutic use)
  • Animals
  • Antineoplastic Agents (pharmacokinetics, therapeutic use)
  • Benzamides (therapeutic use)
  • Drug Resistance, Neoplasm
  • Fusion Proteins, bcr-abl (antagonists & inhibitors, genetics)
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy)
  • Leukemia, Myeloid, Chronic-Phase (drug therapy)
  • Nitriles (pharmacokinetics, therapeutic use)
  • Piperazines (therapeutic use)
  • Protein Kinase Inhibitors (therapeutic use)
  • Protein-Tyrosine Kinases (antagonists & inhibitors)
  • Pyrimidines (therapeutic use)
  • Quinolines (pharmacokinetics, therapeutic use)

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