Nelarabine:嘌呤抗代谢物抗肿瘤药。

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布依LW,爱泼斯坦党卫军,林德利厘米

Nelarabine:嘌呤抗代谢物抗肿瘤药。

其他。2007年9月,29 (9):1887 - 99。

PubMed ID

18035189 (在PubMed

]

文摘

背景:Nelarabine通过美国食品和药物管理局(FDA)在2005年10月治疗t细胞急性淋巴细胞白血病(t)和t细胞淋巴细胞淋巴瘤(T-LBL)没有回应或者至少2化疗方案治疗后复发。目的:本文综述了药理学、作用机制、药代动力学和药效学nelarabine的属性。还综述了nelarabine在所有的临床疗效,T-LBL,和其他血液恶性肿瘤;其毒性、剂量和管理;和地区正在进行的和未来的研究。必威国际app方法:相关文献是通过搜索发现的MEDLINE(1966 - 2007年4月),国际制药抽象(1970 -必威国际app 2007年4月),和美国血液学会数据库(2003 - 2006)使用条款nelarabine Arranon, 506 u78, 2-amino-6-methoxypurine阿拉伯糖苷。确定文章的引用列表寻找额外的来源。必威国际app从nelarabine制造商获得产品信息咨询,FDA nelarabine的评论。所有确定的出版物被认为,这些会议包括本文的目标。结果:Nelarabine,可溶性药物前体9-beta-D——arabinofuranosylguanine (ara-G)是一种新型的嘌呤抗代谢物抗肿瘤药,优先在t细胞积累。 Ara-G is rapidly phosphorylated in T-cells to ara-G triphosphate (ara-GTP), which exerts cytotoxic effects. Renal elimination of ara-G is decreased in patients with mild to moderate renal impairment; however, no dose adjustment is recommended. Accumulation of ara-GTP occurs in T-cells in a dose-dependent manner, leading to preferential cytotoxicity. Nelarabine has activity in T-cell malignancies, as evaluated in 2 Phase I and 5 Phase II studies. It received accelerated approval from the FDA based on the resuits of 2 Phase II trials, one in pediatric patients (PGAA 2001) and the other in adults (CALGB 19801). In PGAA 2001, patients with T-ALL in first relapse (n = 33) had an objective response rate of 55% (16 with a complete response [CR] and 2 with a partial response [PR]), and those with T-ALL in second relapse (n = 30) had an objective response rate of 27% (7 CR and 1 PR). Among patients with central nervous system-positive T-ALL or T-cell non-Hodgkins lymphoma (T-NHL) (n = 21), 33% had an objective response (5 CR and 2 PR); among patients with T-ALL or T-NHL with extramedullary relapse (n = 22), 14% had a PR. CALGB 19801 included 39 adult patients with T-cell malignancies, of whom 7 (18%) had a CR and an additional 2 (5%) had a CR without full hematologic recovery. The recommended dose of nelarabine in adults is 1500 mg/m(2) IV given over 2 hours on days 1, 3, and 5, repeated every 21 days; the recommended dose in pediatric patients is 650 mg/m(2) IV given over 1 hour for 5 consecutive days, repeated every 21 days. Dose-limiting toxicities observed in the Phase I and II trials included central and peripheral neurotoxicity. Symptoms of central neurotoxicity included somnolence, seizures, dizziness, confusion, and ataxia; symptoms of peripheral neurotoxicity included paresthesias, pain in the extremities, and peripheral neuropathy. CONCLUSIONS: Nelarabine is indicated for the treatment of T-ALL and T-LBL that has not responded to or has relapsed after treatment with at least 2 chemotherapy regimens. Objective response rates in Phase II clinical trials of nelarabine have ranged from 11% to 60%. Use of nelarabine is limited by potentially severe neurotoxicity.

DrugBank数据引用了这篇文章

药物

Nelarabine

药物靶点

药物	目标	类	生物	药理作用	行动
Nelarabine	DNA	核苷酸	人类	是的	纳入和不稳定	细节
Nelarabine	DNA连接酶1	蛋白质	人类	是的	抑制剂	细节
Nelarabine	DNA聚合酶α催化亚基	蛋白质	人类	是的	抑制剂	细节
Nelarabine	DNA引物酶小亚基	蛋白质	人类	是的	抑制剂	细节
Nelarabine	Ribonucleoside-diphosphate还原酶大亚基	蛋白质	人类	是的	抑制剂	细节

药物酶

药物	酶	类	生物	药理作用	行动
Nelarabine	腺苷脱氨酶	蛋白质	人类	没有	底物	细节
Nelarabine	脱氧胞苷激酶	蛋白质	人类	没有	底物	细节
Nelarabine	脱氧鸟苷激酶,线粒体	蛋白质	人类	没有	底物	细节