title: Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL.
abstract: BACKGROUND
  Resistance to imatinib mesylate can occur in chronic myelogenous leukemia (CML). Preclinical in vitro studies have shown that nilotinib (AMN107), a new BCR-ABL tyrosine kinase inhibitor, is more potent than imatinib against CML cells by a factor of 20 to 50.
  
  
  METHODS
  In a phase 1 dose-escalation study, we assigned 119 patients with imatinib-resistant CML or acute lymphoblastic leukemia (ALL) to receive nilotinib orally at doses of 50 mg, 100 mg, 200 mg, 400 mg, 600 mg, 800 mg, and 1200 mg once daily and at 400 mg and 600 mg twice daily.
  
  
  RESULTS
  Common adverse events were myelosuppression, transient indirect hyperbilirubinemia, and rashes. Of 33 patients with the blastic phase of disease, 13 had a hematologic response and 9 had a cytogenetic response; of 46 patients with the accelerated phase, 33 had a hematologic response and 22 had a cytogenetic response; 11 of 12 patients with the chronic phase had a complete hematologic remission.
  
  
  CONCLUSIONS
  Nilotinib has a relatively favorable safety profile and is active in imatinib-resistant CML. (ClinicalTrials.gov number, NCT00109707 [ClinicalTrials.gov].).
authors.affiliation: Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX 77230-1402, USA. hkantarj@mdanderson.org
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Francis
authors.initials: F
authors.lastname: Giles
authors.forename: Lydia
authors.initials: L
authors.lastname: Wunderle
authors.forename: Kapil
authors.initials: K
authors.lastname: Bhalla
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Barbara
authors.initials: B
authors.lastname: Wassmann
authors.forename: Chiaki
authors.initials: C
authors.lastname: Tanaka
authors.forename: Paul
authors.initials: P
authors.lastname: Manley
authors.forename: Patricia
authors.initials: P
authors.lastname: Rae
authors.forename: William
authors.initials: W
authors.lastname: Mietlowski
authors.forename: Kathy
authors.initials: K
authors.lastname: Bochinski
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochhaus
authors.forename: James D
authors.initials: JD
authors.lastname: Griffin
authors.forename: Dieter
authors.initials: D
authors.lastname: Hoelzer
authors.forename: Maher
authors.initials: M
authors.lastname: Albitar
authors.forename: Margaret
authors.initials: M
authors.lastname: Dugan
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Leila
authors.initials: L
authors.lastname: Alland
authors.forename: Oliver G
authors.initials: OG
authors.lastname: Ottmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001549:Benzamides; D019008:Drug Resistance, Neoplasm; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010879:Piperazines; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; C406060:abl-bcr fusion protein, human; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib