title: Nilotinib for the treatment of Philadelphia-chromosome-positive chronic myeloid leukemia.
abstract: BACKGROUND
  Although the introduction of imatinib revolutionized the management of chronic myeloid leukemia (CML), some patients exhibit resistance or intolerance to the drug. Nilotinib induces high and rapid rates of cytogenetic and molecular responses. With recent approval for newly diagnosed patients with chronic phase CML, the current algorithm for treatment will probably be transformed.
  
  
  METHODS
  This review will describe evaluations of nilotinib in all phases of CML from 1995 to the present. Early preclinical data and Phase I, Phase II and Phase III evaluations will demonstrate the role of nilotinib in newly diagnosed CML, as well as in imatinib-resistant or imatinib-intolerant disease.
  
  
  RESULTS
  Mutations in the BCR-ABL kinase domain are responsible for the majority of resistance to imatinib. In comparison with imatinib, nilotinib displays increased selectivity and potency at inhibiting proliferation of BCR-ABL expressing cells. Although several mutations, including T315I, remain resistant to nilotinib, activity in all phases of CML has been reported.
  
  
  CONCLUSIONS
  Nilotinib induces high and rapid rates of cytogenetic and molecular response, with less progression to advanced forms of disease compared with imatinib. Considering that the rapid achievement of these clinical milestones has been associated with positive long-term outcomes, nilotinib as initial therapy in patients with CML in chronic phase represents the future in CML treatment. Longer follow-up is necessary to recognize survival advantages.
authors.affiliation: The University of Texas, M.D. Anderson Cancer Center, Department of Leukemia, Houston, 77030, USA.
authors.forename: Amber
authors.initials: A
authors.lastname: Fullmer
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001549:Benzamides; D019008:Drug Resistance, Neoplasm; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000503:physiopathology; D010879:Piperazines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D011743:Pyrimidines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; C498826:nilotinib