Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL
Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL
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DOI：
10.1056/nejmoa055104
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发表时间：
2006-06-15
影响因子：
158.5
通讯作者：
Ottmann, Oliver G.
中科院分区：
文献类型：
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作者：
Kantarjian, Hagop;Giles, Francis;Ottmann, Oliver G.
背景：甲磺酸伊马替尼耐药可发生在慢性粒细胞白血病（CML）。临床前体外研究表明，尼洛替尼（AMN 107）是一种新型的BCR-ABL酪氨酸激酶抑制剂，其抗CML细胞的作用比伊马替尼强20 ~ 50倍。方法：在一项I期剂量递增研究中，我们将119例伊马替尼耐药的CML或急性淋巴细胞白血病（ALL）患者分为两组，分别口服尼洛替尼50 mg、100 mg、200 mg、400 mg、600 mg、800 mg和1200 mg，每日1次和400 mg和600 mg，每日2次。在33例急变期患者中，13例有血液学反应，9例有细胞遗传学反应;在46例加速期患者中，33例有血液学反应，22例有细胞遗传学反应; 12例慢性期患者中有11例完全血液学缓解。
BACKGROUND:Resistance to imatinib mesylate can occur in chronic myelogenous leukemia (CML). Preclinical in vitro studies have shown that nilotinib (AMN107), a new BCR-ABL tyrosine kinase inhibitor, is more potent than imatinib against CML cells by a factor of 20 to 50.METHODS:In a phase 1 dose-escalation study, we assigned 119 patients with imatinib-resistant CML or acute lymphoblastic leukemia (ALL) to receive nilotinib orally at doses of 50 mg, 100 mg, 200 mg, 400 mg, 600 mg, 800 mg, and 1200 mg once daily and at 400 mg and 600 mg twice daily.RESULTS:Common adverse events were myelosuppression, transient indirect hyperbilirubinemia, and rashes. Of 33 patients with the blastic phase of disease, 13 had a hematologic response and 9 had a cytogenetic response; of 46 patients with the accelerated phase, 33 had a hematologic response and 22 had a cytogenetic response; 11 of 12 patients with the chronic phase had a complete hematologic remission.CONCLUSIONS:Nilotinib has a relatively favorable safety profile and is active in imatinib-resistant CML.