一个第一阶段研究CDK4/6抑制剂 ribociclib与gemcitabine结合在患有晚期固体瘤的患者中
Aurora Norman1, Mahesh Seetharam2, Jacob Allred1
1Mayo Clinic, Rochester, MN, USA.
BJC reports
|January 14, 2025
概括
里博西克利布和格姆西塔宾的组合显示在先进的固体瘤中具有良好的耐受性和瘤稳定性. 像Rb状态这样的生物标志物可以识别出从这种化疗方案中受益最多的患者.
科学领域:
- 在瘤学瘤学.
- 临床药理学 临床药理学
背景情况:
- 临床前研究表明,CDK4/6抑制剂与凝胺之间存在协同作用.
- 这导致了对 ribociclib 与 gemcitabine 结合的研究.
研究的目的:
- 为了确定 ribociclib 加上 gemcitabine 的最大耐受剂量 (MTD) 和剂量限制性毒性 (DLT).
- 评估这种组合在患有晚期固体瘤的患者中的安全性和有效性.
主要方法:
- 进行了一项单臂,多队列的I期临床试验.
- 患者在第1天和第8天接受静脉注射凝丁,然后在第8至14天接受口服里博西基利布,每3周重复一次.
主要成果:
- MTD和推的II期剂量 (RP2D) 已确定为每天800毫克的里博西基布和1000毫克/m2.
- 最常见的3级不良事件包括中性质减退,血小板减退和贫血.
- 没有观察到部分或完全的反应;然而,在MTD的有效性可评估患者中,68%的患者实现了稳定的疾病.
结论:
- рибоцилиб 和 gemcitabine 的组合被很好地容忍,并证明了瘤的稳定性.
- 诸如Rb状态和CDK2/4/6活性等生物标志物可能有助于选择可能受益于这种联合治疗的患者.
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