title: Efficacy and safety of nilotinib in Japanese patients with imatinib-resistant or -intolerant Ph+ CML or relapsed/refractory Ph+ ALL: a 36-month analysis of a phase I and II study.
abstract: Although the tyrosine kinase inhibitor (TKI) imatinib is often used as first-line therapy for newly diagnosed chronic myelogenous leukemia (CML), some patients fail to respond, or become intolerant to imatinib. Nilotinib is a potent and selective second-generation TKI, with confirmed efficacy and tolerability in patients with imatinib-resistant or -intolerant CML. A phase I/II study was conducted in Japanese patients with imatinib-resistant or -intolerant CML or relapsed/refractory Ph+ acute lymphoblastic leukemia. Thirty-four patients were treated with nilotinib for up to 36 months. Major cytogenetic response was achieved in 15/16 patients (93.8%) with chronic-phase CML within a median of approximately 3 months. Major molecular response was achieved in 13/16 patients (81.3%). These responses were sustained at the time of the most recent evaluation in 13 patients and 11 patients, respectively. Hematologic and cytogenetic responses were also observed in patients with advanced CML. The BCR-ABL mutation associated with the most resistance to available TKIs, T315I, was observed in three patients. Common adverse events included rash, nasopharyngitis, leukopenia, neutropenia, thrombocytopenia, nausea, headache and vomiting. Most adverse events resolved following nilotinib dose interruptions/reductions. These results support the favorable long-term efficacy and tolerability of nilotinib in Japanese patients with imatinib-resistant or -intolerant chronic-phase chronic myeloid leukemia.
authors.affiliation: Division of Hematology, NTT Kanto Medical Center, 5-9-22 Higashigotanda, Shinagawa-ku, Tokyo, Japan. usuki@east.ntt.co.jp
authors.forename: Kensuke
authors.initials: K
authors.lastname: Usuki
authors.forename: Arinobu
authors.initials: A
authors.lastname: Tojo
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Maeda
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Akira
authors.initials: A
authors.lastname: Matsuda
authors.forename: Kazuma
authors.initials: K
authors.lastname: Ohyashiki
authors.forename: Chiaki
authors.initials: C
authors.lastname: Nakaseko
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: Shinichiro
authors.initials: S
authors.lastname: Okamoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Oritani
authors.forename: Masaya
authors.initials: M
authors.lastname: Okada
authors.forename: Noriko
authors.initials: N
authors.lastname: Usui
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nagai
authors.forename: Taro
authors.initials: T
authors.lastname: Amagasaki
authors.forename: Aira
authors.initials: A
authors.lastname: Wanajo
authors.forename: Tomoki
authors.initials: T
authors.lastname: Naoe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D020732:Cytogenetic Analysis; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000187:drug effects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib