A Phase I/II study of nilotinib in Japanese patients with imatinib-resistant or -intolerant Ph+ CML or relapsed/refractory Ph+ ALL.
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.
Tojo
Arinobu
A
The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. a-tojo@ims.u-tokyo.ac.jp
Usuki
Kensuke
K
Urabe
Akio
A
Maeda
Yasuhiro
Y
Kobayashi
Yukio
Y
Jinnai
Itsuro
I
Ohyashiki
Kazuma
K
Nishimura
Miki
M
Kawaguchi
Tatsuya
T
Tanaka
Hideo
H
Miyamura
Koichi
K
Miyazaki
Yasushi
Y
Hughes
Timothy
T
Branford
Susan
S
Okamoto
Shinichiro
S
Ishikawa
Jun
J
Okada
Masaya
M
Usui
Noriko
N
Tanii
Hiromi
H
Amagasaki
Taro
T
Natori
Hiroko
H
Naoe
Tomoki
T
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
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib