早期更高的血雷戈拉费尼布度预测了日本mCRC患者的短PFS
Kazuo Kobayashi1, Takeru Wakatsuki2, Erika Sugiyama3
1Department of Pharmacy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
Clinical and translational science
|November 5, 2025
概括
在转移性结直肠癌患者中,高度的regorafenib与较短的无进展生存期和增加的毒性相关. 早期监测regorafenib水平对于优化治疗和管理不良事件至关重要.
科学领域:
- 药理学 药理学是指药理学的学科.
- 在瘤学瘤学.
背景情况:
- 瑞戈拉费尼布的药理动力学和代谢物度在不同患者之间存在显著差异.
- 转移性结直肠癌 (mCRC) 血水平与治疗结果之间的关系尚未明确.
研究的目的:
- 在mCRC患者中调查regorafenib及其活性代谢物 (M2,M5) 的早期血度与无进展生存期 (PFS) 之间的相关性.
- 评估regorafenib水平与治疗毒性之间的关联.
主要方法:
- 对33名mCRC患者进行前性研究,这些患者接受了第三线或后期治疗的regorafenib.
- 血液样本采集于周期1,第7天,通过液体染色学-双重质谱测量测量雷戈拉费尼布,M2和M5的最低度 (Ctrough).
- 对Ctrough水平和PFS之间的相关性分析,以及对不良事件和恢复治疗率的评估.
主要成果:
- 中位数的PFS为70天. 在regorafenib Ctrough和PFS之间观察到一个反向相关性 (r = -0.394,p = 0.023).
- 具有regorafenib含量≥2848.4ng/mL的患者的PFS显著较短 (35比95天,HR3.23,p=0.002).
- 较高的regorafenib水平与更频繁的严重不良事件 (30.0%与4.3%相比),中性粒细胞与淋巴细胞的比率增加 (p = 0.031) 和较低的治疗恢复率 (16.7%与88.9%,p = 0.003) 相关.
结论:
- 在mCRC患者中,早期高血水平的regorafenib与较短的PFS有关.
- 快速增加的regorafenib水平可能导致严重的毒性和全身炎症,可能会影响治疗疗效.
- 在治疗早期监测regorafenibCtrough水平可能有助于剂量优化和毒性管理.
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