Phase II study of nelarabine (compound 506U78) in children and young adults with refractory T-Cell malignancies: A report from the children's oncology group
Phase II study of nelarabine (compound 506U78) in children and young adults with refractory T-Cell malignancies: A report from the children's oncology group
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DOI：
10.1200/jco.2005.03.426
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发表时间：
2005-05-20
影响因子：
45.3
通讯作者：
Harris, MB
中科院分区：
文献类型：
--
作者：
Berg, SL;Blaney, SM;Harris, MB
目的奈拉滨（化合物506 U 78）是9-b-d-阿拉伯呋喃糖基鸟嘌呤的水溶性前体药物，在T淋巴母细胞中被转化为ara-GTP。患者和方法我们进行了一项II期研究，患者分层如下：第2层>= 25%的骨髓原始细胞首次复发;第2层>= 25%的骨髓原始细胞首次复发;第3层>= 25%的骨髓原始细胞首次复发;第4层>= 25%的骨髓原始细胞首次复发。第二次复发;第3层：阳性CSF;第4层：髓外（非CNS）复发。初始奈拉滨剂量为1.2 g/m2/d，连续5天，每3周一次。在这项或其他研究中，由于神经毒性，有两次剂量递减。第1层和第2层患者的最终剂量为650 mg/m2/d，第3层和第4层患者的最终剂量为400 mg/m2/d。最终剂量水平的完全加部分缓解率为：第1层为55%;第2层为27%;第3层为33%;第4层为14%。结论奈拉滨单药治疗复发性T细胞白血病疗效显著，首次骨髓复发有效率达50%以上。与奈拉滨给药相关的最显著不良事件是神经系统。计划进行进一步的研究，以确定在儿童T细胞白血病的一线治疗中加入奈拉滨是否会改善生存率。
Purpose Nelarabine (compound 506U78), a water soluble prodrug of 9-b-d-arabinofuranosylguanine, is converted to ara-GTP in T lymphoblasts. We sought to define the response rate of nelarabine in children and young adults with refractory or recurrent T-cell disease.Patients and Methods We performed a phase II study with patients stratified as follows: stratum 2 >= 25 % bone marrow blasts in first relapse; stratum 2 >= 25 % bone marrow blasts in ! second relapse; stratum 3: positive CSF; stratum 4: extramedullary (non-CNS) relapse. The initial nelarabine dose was 1.2 g/m(2) daily for 5 consecutive days every 3 weeks. There were two dose de-escalations due to neurotoxicity on this or other studies. The final dose was 650 mg/m(2)/d for strata 1 and two patients and 400 mg/m(2)/d for strata 3 and four patients.Results We enrolled 121 patients (106 assessable for response) at the final dose levels. Complete plus partial response rates at the final dose levels were: 55 % in stratum 1; 27 % in stratum 2; 33 % in stratum 3; and 14 % in stratum 4. There were 31 episodes of >= grade 3 neurologic adverse events in 27 patients (18 % of patients).Conclusion Nelarabine is active as a single agent in recurrent T-cell leukemia, with a response rate more than 50 % in first bone marrow relapse. The most significant adverse events associated with nelarabine administration are neurologic. Further studies are planned to determine whether the addition of nelarabine to front-line therapy for T-cell leukemia in children will improve survival.