A Phase I/II study of nilotinib in Japanese patients with imatinib-resistant or -intolerant Ph plus CML or relapsed/refractory Ph plus ALL
A Phase I/II study of nilotinib in Japanese patients with imatinib-resistant or -intolerant Ph plus CML or relapsed/refractory Ph plus ALL
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DOI：
10.1007/s12185-009-0327-0
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发表时间：
2009-06-01
影响因子：
2.1
通讯作者：
Naoe, Tomoki
中科院分区：
文献类型：
--
作者：
Tojo, Arinobu;Usuki, Kensuke;Naoe, Tomoki
尼罗替尼是第二代BCR-ABL激酶抑制剂，与伊马替尼相比，具有更好的效力和选择性。一项I/II期剂量递增研究旨在评估尼洛替尼在日本伊马替尼耐药或不耐受费城染色体阳性（Ph+）慢性粒细胞白血病（CML）或复发/难治性Ph+急性淋巴细胞白血病（ALL）患者中的疗效、安全性和药代动力学。该分析共评估了34例患者，中位药物暴露持续时间为293天（范围13-615天）。6例基线时没有完全血液学反应（CHR）的CML-CP患者均迅速达到了完全血液学反应。94%的CML-CP患者实现了主要的细胞遗传学应答，其中69%的患者实现了完全的细胞遗传学应答。主要分子反应率达到56%。在晚期CML和Ph+ ALL患者中也观察到这些反应。非血液学不良事件多为轻至中度。3级或4级中性粒细胞减少和血小板减少分别发生在50%和28%的患者中。总的来说，这项研究的结果表明，尼罗替尼对伊马替尼耐药或不耐受的CML- cp和晚期和Ph+ ALL的CML患者有显著的疗效。本研究结果证实了尼洛替尼在日本患者中的有效性和安全性。
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.