title: Bosutinib for the treatment of chronic myeloid leukemia in chronic phase.
abstract: The clinical outcome for patients with chronic myeloid leukemia in chronic phase (CML-CP) is currently very favorable due to the availability of tyrosine kinase inhibitors (TKIs) that are well tolerated and effectively suppress the constitutively activated BCR-ABL1 kinase that underlies the pathogenesis of this malignancy. Three TKIs -imatinib, nilotinib and dasatinib- have been approved as frontline therapy in CML-CP. Another TKI, bosutinib, inhibits with high potency numerous tyrosine kinases, including BCR-ABL1, Src family of kinases and MAPK, among others. Like nilotinib and dasatinib, bosutinib is a second-generation TKI that inhibits the majority of mutations associated with imatinib resistance, with the exception of T315I. In patients with CML-CP with prior intolerance or resistance to imatinib therapy, bosutinib rendered response rates similar to those observed in the same patient population treated with nilotinib or dasatinib. Preliminary results from the ongoing phase III BELA study in which bosutinib is compared in a randomized fashion to imatinib for patients with newly diagnosed CML-CP have been recently reported. We herein summarize the preclinical and clinical experience of bosutinib in CML.
authors.affiliation: Department of Leukemia, Unit 428, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: A
authors.initials: A
authors.lastname: Quintás-Cardama
authors.forename: H
authors.initials: H
authors.lastname: Kantarjian
authors.forename: J
authors.initials: J
authors.lastname: Cortes
mesh_terms: D000814:Aniline Compounds / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001549:Benzamides; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D009570:Nitriles / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use; D011804:Quinolines / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D017211:Treatment Failure
chemical_list: D000814:Aniline Compounds; D001549:Benzamides; D009570:Nitriles; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011804:Quinolines; C471992:bosutinib; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases