Chronic Myeloid Leukemia and Second-Generation Tyrosine Kinase Inhibitors: When, How, and Which One?
Chronic Myeloid Leukemia and Second-Generation Tyrosine Kinase Inhibitors: When, How, and Which One?
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DOI：
10.1053/j.seminhematol.2010.06.002
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发表时间：
2010-10-01
影响因子：
3.6
通讯作者：
Cortes, Jorge
中科院分区：
文献类型：
--
作者：
Jabbour, Elias;Kantarjian, Hagop;Cortes, Jorge
慢性粒细胞白血病（CML）是一种进行性的，往往是致命的骨髓增生性疾病。伊马替尼是一种特异性针对BCR-ABL的酪氨酸激酶抑制剂（TKI），它的引入是CML治疗的重大突破。虽然大多数患者对伊马替尼一线治疗有反应，但有些患者会出现反应丧失（耐药）或因毒性（不耐受）而需要停止治疗。对于标准剂量伊马替尼治疗失败的患者，伊马替尼剂量递增是二线选择。然而，高剂量伊马替尼并不是发生药物毒性的患者的合适方法，并且对于该策略实现的反应的持久性仍存在问题。替代的二线选择包括较新的TKI达沙替尼和尼洛替尼。有大量关于这些药物的长期数据。虽然两者都是强效和特异性BCR-ABL TKI，但达沙替尼和尼洛替尼表现出独特的药理学特征和相对于不同患者特征（如疾病分期和BCR-ABL突变状态）的反应模式。为了优化治疗效果，临床医生应根据每个患者的历史反应、不良事件耐受水平和风险因素选择治疗。Semin Hematol 47：344-353。(C)2010年由Elsevier Inc.出版
Chronic myeloid leukemia (CML) is a progressive and often fatal myeloproliferative disorder. The introduction of imatinib, a tyrosine kinase inhibitor (TKI) specific for BCR-ABL, was a major breakthrough in CML therapy. Although most patients respond to first-line imatinib therapy, some experience a loss of response (resistance) or require treatment discontinuation due to toxicity (intolerance). For patients who fail with standard-dose imatinib therapy, imatinib dose escalation is a second-line option. However, high-dose imatinib is not an appropriate approach for patients experiencing drug toxicity, and there remain questions over the durability of responses achieved with this strategy. Alternative second-line options include the newer TKIs dasatinib and nilotinib. A substantial amount of long-term data for these agents is available. Although both are potent and specific BCR-ABL TKIs, dasatinib and nilotinib exhibit unique pharmacological profiles and response patterns relative to different patient characteristics, such as disease stage and BCR-ABL mutational status. To optimize therapeutic benefit, clinicians should select treatment based on each patient's historical response, adverse-event tolerance level, and risk factors. Semin Hematol 47:344-353. (C) 2010 Published by Elsevier Inc.