title: A Phase I/II study of nilotinib in Japanese patients with imatinib-resistant or -intolerant Ph+ CML or relapsed/refractory Ph+ ALL.
abstract: Nilotinib is a second-generation BCR-ABL kinase inhibitor with improved potency and selectivity compared to imatinib. A Phase I/II dose-escalation study was designed to evaluate the efficacy, safety, and pharmacokinetics of nilotinib in Japanese patients with imatinib-resistant or -intolerant Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) or relapsed/refractory Ph+ acute lymphoblastic leukemia (ALL). A total of 34 patients were evaluated in this analysis and had a median duration of drug exposure of 293 (range 13-615) days. All 6 CML-CP patients without complete hematologic response (CHR) at baseline rapidly achieved CHR. A major cytogenetic response was achieved in 94% of patients with CML-CP, including a complete cytogenetic response in 69%. A major molecular response was achieved by 56%. These responses were also observed in patients with CML in advanced stages and Ph+ ALL. Non-hematologic adverse events were mostly mild to moderate. Grade 3 or 4 neutropenia and thrombocytopenia occurred in 50 and 28% of patients, respectively. Overall, the results of this study suggest that nilotinib induced significant responses in imatinib-resistant or -intolerant patients with CML-CP and CML in advanced stages and Ph+ ALL. The results of this study confirmed the efficacy and safety of nilotinib in Japanese patients.
authors.affiliation: The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. a-tojo@ims.u-tokyo.ac.jp
authors.forename: Arinobu
authors.initials: A
authors.lastname: Tojo
authors.forename: Kensuke
authors.initials: K
authors.lastname: Usuki
authors.forename: Akio
authors.initials: A
authors.lastname: Urabe
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Maeda
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Itsuro
authors.initials: I
authors.lastname: Jinnai
authors.forename: Kazuma
authors.initials: K
authors.lastname: Ohyashiki
authors.forename: Miki
authors.initials: M
authors.lastname: Nishimura
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kawaguchi
authors.forename: Hideo
authors.initials: H
authors.lastname: Tanaka
authors.forename: Koichi
authors.initials: K
authors.lastname: Miyamura
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: Timothy
authors.initials: T
authors.lastname: Hughes
authors.forename: Susan
authors.initials: S
authors.lastname: Branford
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Okamoto
authors.forename: Jun
authors.initials: J
authors.lastname: Ishikawa
authors.forename: Masaya
authors.initials: M
authors.lastname: Okada
authors.forename: Noriko
authors.initials: N
authors.lastname: Usui
authors.forename: Hiromi
authors.initials: H
authors.lastname: Tanii
authors.forename: Taro
authors.initials: T
authors.lastname: Amagasaki
authors.forename: Hiroko
authors.initials: H
authors.lastname: Natori
authors.forename: Tomoki
authors.initials: T
authors.lastname: Naoe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D044466:Asian People; 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 / Q000493:pharmacokinetics / Q000633:toxicity; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D016879:Salvage Therapy; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib