NCI 7977:一期剂量升级研究中断性口服ABT-888 (Veliparib) 加上静脉静脉注射的伊诺基坦在患有高级固体瘤的患者中进行
Michael Cecchini1, Zenta Walther2, Wei Wei3
1Department of Internal Medicine (Medical Oncology), Yale University School of Medicine, New Haven, Connecticut.
Cancer research communications
|June 28, 2023
概括
这项研究发现,结合维利巴里布 (一种PARP抑制剂) 和氨基酸氨基酸对进一步发展过于有毒,尽管一些患者患有稳定的疾病. 未来的研究应该探索具有更好的耐受性的PARP抑制剂组合.
科学领域:
- 在瘤学瘤学.
- 临床药理学 临床药理学
背景情况:
- 维利帕里布是一种PARP抑制剂 (PARPi),在BRCA缺乏的瘤中表现出活性.
- 临床前数据表明,PARPi与胺酶抑制剂 (如伊利诺特干) 之间有协同作用,而不考虑同源复合缺陷 (HRD).
研究的目的:
- 在一期临床试验 (NCI 7977) 中评估韦利帕里布与义利诺坦联合的安全性和有效性.
- 为了确定间歇性韦利巴里布和伊利诺特干的最大耐受剂量 (MTD),在患有固体瘤的患者中.
主要方法:
- 一个多队列I期试验在1至4天和8至11天给予越来越高的维利帕里布 (50毫克或100毫克每天两次) 和21天周期的第3天和第10天给予氨基酸 (100毫克/米2).
- 对剂量限制性毒性 (DLT) 进行了评估,以确定MTD.
主要成果:
- 确定的MTD是每天两次服用维利帕里布50毫克,同时服用伊利诺特干100毫克/m2.
- 观察到3级中性质减退和腹作为DLT.
- 没有发现客观反应,但4名患者的无进展生存时间超过6个月.
结论:
- 间歇性韦利帕里布和每周一次的伊利诺特干的组合被发现是太有毒,无法进一步临床开发.
- 未来的PARPi组合需要具有不重叠毒性的药物来提高患者的耐受性.
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