Medical University of South Carolina, Hematology and Oncology, 96 Jonathan Lucas Street, CSB 903, Charleston, SC 29425, USA.
Expert Opin Investig Drugs. 2010 Mar;19(3):427-36. doi: 10.1517/13543781003598862.
Internal tandem duplication of the fms-like tyrosine kinase 3 (FLT3) gene (FLT3-ITD) is a common recurring mutation in acute myeloid leukemia (AML) with normal karyotype, and the presence of FLT3-ITD confers a poor prognosis on this large subgroup of AML patients. Since the discovery of lestaurtinib as a potent FLT3 inhibitor, in 1985, there has been considerable interest in the development of this agent (CEP-701, Cephalon, Frazer, PA, USA) for treatment of this population.
An extensive literature search was conducted that included published articles and abstracts on the preclinical and clinical development of this agent spanning the last decade.
The review describes the historical development of this agent and reviews the available preclinical and clinical data on lestaurtinib and expands on potential future directions in development of this agent.
Lestaurtinib is a multi targeted tyrosine kinase inhibitor which has been shown to potently inhibit FLT3 at nanomolar concentrations in preclinical studies, leading to its rapid development as a potential targeted agent for treatment of AML. Phase I studies have shown lestaturtinib to be an active agent particularly when used in combination with cytotoxic drugs. Currently, Phase II and Phase III studies are underway aiming to establish the future of this agent as a treatment option for patients with FLT3-ITD AML.
内部串联重复的 fms 样酪氨酸激酶 3（FLT3）基因（FLT3-ITD）是急性髓系白血病（AML）中常见的常染色体核型反复突变，FLT3-ITD 的存在对这一大组 AML 患者预后不良。自 1985 年发现 lestaurtinib 作为一种有效的 FLT3 抑制剂以来，人们对该药物（CEP-701，Cephalon，Frazer，PA，USA）在该人群中的治疗开发产生了浓厚的兴趣。
进行了广泛的文献检索，包括过去十年中关于该药物的临床前和临床开发的已发表文章和摘要。
综述描述了该药物的历史发展，并回顾了 lestaurtinib 的现有临床前和临床数据，并扩展了该药物开发的潜在未来方向。
Lestaurtinib 是一种多靶点酪氨酸激酶抑制剂，在临床前研究中已被证明能以纳摩尔浓度有效地抑制 FLT3，因此迅速成为治疗 AML 的潜在靶向药物。I 期研究表明，lestaurtinib 是一种有效的药物，特别是与细胞毒性药物联合使用时。目前，正在进行 II 期和 III 期研究，旨在确定该药物作为 FLT3-ITD AML 患者治疗选择的未来。
