Sprycel for chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia resistant to or intolerant of imatinib mesylate
Sprycel for chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia resistant to or intolerant of imatinib mesylate
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DOI：
10.1158/1078-0432.ccr-07-4175
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发表时间：
2008-01-15
影响因子：
11.5
通讯作者：
Pazdur, Richard
中科院分区：
文献类型：
--
作者：
Brave, Michael;Goodman, Vicki;Pazdur, Richard
目的：2006年6月28日，美国食品和药物管理局批准达沙替尼（Sprycel; Bristol-Myers Squibb），一种新型的多种酪氨酸激酶的小分子抑制剂，用于治疗成人慢性期、加速期、或髓系或淋巴母细胞期慢性髓系白血病（CML）或费城染色体阳性急性淋巴细胞白血病（Ph+ ALL）对既往治疗（包括伊马替尼）有耐药或不耐受。实验设计：四项单臂多中心研究支持达沙替尼的疗效和安全性。慢性期CIVIL的主要疗效终点为主要细胞遗传学缓解。加速期、髓系期和淋巴母细胞期CML以及Ph+ ALL的主要终点是主要血液学应答。在慢性期CIVIL患者中，主要细胞遗传学缓解率为45%，完全细胞遗传学缓解率为33%。加速期CIVIL、髓系CIVIL、淋巴母细胞CIVIL和Ph+ ALL患者的主要血液学缓解率分别为59%、32%、31%和42%。慢性期、加速期和骨髓期CIVIL的中位缓解持续时间尚未达到。主要血液学缓解的中位持续时间在淋巴母细胞CIVIL中为3.7个月，在Ph+ ALL中为4.8个月。达沙替尼的常见毒性包括骨髓抑制，出血和液体retention.Conclusions：本报告描述了美国食品和药物管理局的审查支持批准达沙替尼CIVIL和Ph+ ALL的基础上的速率和持久性的细胞遗传学和血液学反应。
Purpose: On June 28, 2006, the U.S. Food and Drug Administration approved dasatinib (Sprycel; Bristol-Myers Squibb), a new small-molecule inhibitor of multiple tyrosine kinases, for the treatment of adults with chronic phase, accelerated phase, or myeloid or lymphoid blast phase chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy including imatinib. This summary reviews the database supporting this approval.Experimental Design: Four single-arm multicenter studies supported the efficacy and safety of dasatinib. The primary efficacy end point in chronic phase CIVIL was major cytogenetic response. The primary end point in accelerated phase, myeloid phase, and lymphoid blast phase CML, and Ph+ ALL was major hematologic response.Results: The four studies combined enrolled 445 patients. In patients with chronic phase CIVIL, the major cytogenetic response rate was 45% with a complete cytogenetic response rate of 33%. Major hematologic response rates in patients with accelerated phase CIVIL, myeloid CIVIL, lymphoid blast CIVIL, and Ph+ ALL were 59%, 32%, 31%, and 42%, respectively. Median response durations in chronic phase, accelerated phase, and myeloid phase CIVIL had not been reached. The median durations of major hematologic response were 3.7 months in lymphoid blast CIVIL and 4.8 months in Ph+ ALL. Common toxicities with dasatinib included myelosuppression, bleeding, and fluid retention.Conclusions: This report describes the Food and Drug Administration review supporting the approval of dasatinib for CIVIL and Ph+ ALL based on the rates and durability of cytogenetic and hematologic responses.