A Phase I/II study of nilotinib in Japanese patients with imatinib-resistant or -intolerant Ph plus CML or relapsed/refractory Ph plus ALL

作者：Tojo Arinobu^*; Usuki Kensuke; Urabe Akio; Maeda Yasuhiro; Kobayashi Yukio; Jinnai Itsuro; Ohyashiki Kazuma; Nishimura Miki; Kawaguchi Tatsuya; Tanaka Hideo; Miyamura Koichi; Miyazaki Yasushi; Hughes Timothy; Branford Susan; Okamoto Shinichiro; Ishikawa Jun; Okada Masaya; Usui Noriko; Tanii Hiromi; Amagasaki Taro; Natori Hiroko; Naoe Tomoki

来源：International Journal of Hematology, 2009, 89(5): 679-688.

DOI：10.1007/s12185-009-0327-0

• Nilotinib
• CML
• BCR-ABL
• Imatinib resistant
• Ph plus 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.

• 出版日期2009-6
• 单位河北医科大学