title: Bosutinib: a second-generation tyrosine kinase inhibitor for chronic myelogenous leukemia.
abstract: OBJECTIVE
  To review clinical trials and main characteristics of bosutinib, a second-generation tyrosine kinase inhibitor (TKI) for treatment of chronic myelogenous leukemia (CML).
  
  
  METHODS
  Pertinent data were identified through a search of PubMed (January 1990-April 2013) using the primary search terms SKI-606, bosutinib, and CML. Additionally, preliminary reports published in abstract form by the American Society of Clinical Oncology and American Society of Hematology (January 1990-April 2013) were screened for inclusion.
  
  
  METHODS
  Clinical Phase 1, 2, and 3 studies reported in English evaluating the safety and efficacy of bosutinib in patients with CML were reviewed.
  
  
  RESULTS
  Bosutinib is a TKI of the breakpoint cluster region/Abelson murine leukemia (BCR-ABL) gene approved by the Food and Drug Administration on September 4, 2012, for second-line treatment of chronic phase, accelerated phase, and blast phase CML. In the second-line setting, bosutinib is effective in some patients with CML resistant or intolerant to imatinib, dasatinib, and/or nilotinib, but it is not effective in patients whose disease expresses the T315I point mutation in BCR-ABL. Bosutinib also has been compared with imatinib, the standard first-line treatment, in 502 patients with newly diagnosed chronic phase CML in a Phase 3 trial. Complete cytogenetic response at 12 months, the primary efficacy end point, is similar between bosutinib and imatinib (p = 0.601); therefore, bosutinib is not indicated in the first-line setting. Common adverse events associated with bosutinib include diarrhea, nausea, and vomiting. Grade 3 and 4 adverse events reported in at least 5% of bosutinib-treated patients include elevated serum lipase and liver aminotransferases, anemia, thrombocytopenia, neutropenia, and diarrhea.
  
  
  CONCLUSIONS
  Currently available clinical trials suggest that bosutinib is generally a safe and effective treatment option for patients with CML who have failed first-line TKIs and who do not express the T315I mutation; however, tolerability may be problematic for some patients.
authors.affiliation: National Institutes of Health Clinical Center, Bethesda, MD, USA.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Stansfield
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Hughes
authors.forename: Tracey L
authors.initials: TL
authors.lastname: Walsh-Chocolaad
mesh_terms: D000814:Aniline Compounds / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D004347:Drug Interactions; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D009570:Nitriles / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D011804:Quinolines / Q000627:therapeutic use*
chemical_list: D000814:Aniline Compounds; D000970:Antineoplastic Agents; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011804:Quinolines; C471992:bosutinib
keywords: CML; bosutinib; tyrosine kinase inhibitor