对FDA批准的瘤学小分子的不良事件和剂量强度的景观分析
Keagan P Collins1, Donghua Yin2, Yazdi K Pithavala2
1Clinical Pharmacology and Translational Sciences, Pfizer Worldwide R&D, 10555 Science Center Drive, San Diego, CA, 92121, USA. keaganc010@gmail.com.
Cancer chemotherapy and pharmacology
|January 4, 2025
概括
新的瘤小分子药物显示较低的剂量强度和更多的不良事件,当标签剂量等于最大耐受剂量 (MTD). 这凸显了癌症治疗开发中持续优化剂量的必要性.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
- 药物开发 药物开发
背景情况:
- 新型瘤治疗药物的开发越来越多地集中在分子向药物上.
- 剂量选择已经从基于最大耐受剂量 (MTD) 的方法转移到优化长期耐受性和疗效.
研究的目的:
- 为了评估最近批准的瘤学小分子的耐受性.
- 评估FDA批准的小分子瘤学药物的剂量强度,修改和治疗出现的不良事件 (TEAE).
主要方法:
- 调查了54种FDA批准的小分子瘤学化合物 (自2017年3月以来).
- 分析了剂量强度,剂量修改和TEAE.
- 对标签剂量等于MTD的药物的结果进行比较,而对标签剂量等于MTD的药物的结果进行比较.
主要成果:
- 在54种化合物中,只有15种化合物在标签剂量=MTD时获得批准.
- 标签 剂量 = MTD化合物显示较低的剂量强度和较高的剂量修改由于不良事件.
- 对7种化合物发布了营销后剂量优化要求,对有效性或安全性暴露-反应关系的证据有限.
结论:
- 最近批准的瘤小分子显示出合理的相对剂量强度 (RDI).
- 然而,当标签剂量等于MTD时,严重不良事件 (等级≥3TEAE) 和剂量修改的发生率更高.
- 在开发小分子瘤学治疗中,持续需要剂量优化策略.
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