title: Nilotinib for the treatment of chronic myeloid leukemia.
abstract: The introduction of targeted therapy has revolutionized the treatment of chronic myeloid leukemia (CML). The pivotal role of the Philadelphia chromosome, resulting from the breakpoint cluster region-Abelson (BCR-ABL) translocation, led to the development of imatinib mesylate, a tyrosine kinase inhibitor with significant activity against the BCR-ABL oncoprotein. Unprecedented clinical activity in CML led to rapid approval and established first-line therapy with imatinib mesylate as the standard of care in most patients. However, the occurrence of imatinib resistance or intolerance has sparked the development of newer drugs with increased activity or specificity. Nilotinib is a second-generation tyrosine kinase inhibitor that has been rationally designed on the basis of imatinib. An overview is given on clinical results in imatinib-resistant or -intolerant patients that led to its current approval as second-line therapy for the chronic and accelerated phases of CML. Future studies will address the role of nilotinib as first-line therapy, in combination strategies and in the context of specific BCR-ABL mutations.
authors.affiliation: Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Medizinische Klinik m.S. Hämatologie und Onkologie, Augustenburger Platz 1, 13353 Berlin, Germany. theo.kim@charite.de
authors.forename: Theo Daniel
authors.initials: TD
authors.lastname: Kim
authors.forename: Bernd
authors.initials: B
authors.lastname: Dörken
authors.forename: Philipp
authors.initials: P
authors.lastname: le Coutre
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001549:Benzamides; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D019008:Drug Resistance, Neoplasm; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000191:economics; D010879:Piperazines / Q000191:economics / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011743:Pyrimidines / Q000737:chemistry / Q000191:economics / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; C498826:nilotinib