预测DPYD野生型患者的严重毒性,用基于capecitabine的抗癌疗法治疗的Nomogram
Jonathan E Knikman1,2, Marta Lopez-Yurda3, Didier Meulendijks1,4,5
1Division of Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Clinical pharmacology and therapeutics
|November 13, 2023
概括
一个新的预测模型估计DPYD野生型患者的严重capecitabine毒性风险. 这种工具有助于临床医生在化疗前评估毒性,提高患者的安全.
科学领域:
- 在瘤学瘤学.
- 药物基因组学 药物基因组学
- 临床预测模型临床预测模型
背景情况:
- 根据DPYD指导的剂量提高了胺化疗的安全性.
- 严重的capecitabine毒性影响大约23%的DPYD野生型患者.
- 现有的DPYD变异基因选不能完全缓解capecitabine毒性风险.
研究的目的:
- 开发和验证DPYD野生型癌症患者严重capecitabine相关毒性的预测模型.
- 为了确定与capecitabine毒性相关的患者相关和治疗相关的因素.
- 为DPYD野生型个体提供临床工具,用于风险分层.
主要方法:
- 使用两项大型临床试验 (NCT00838370,NCT02324452) 的数据开发了一个名录.
- 排除具有已知DPYD变体等位基因的患者.
- 预测因素的单变和多变逻辑回归分析,包括年龄,性别,身体表面积,治疗方案和肌水平.
- 使用引导重新抽样和交叉验证进行内部验证.
主要成果:
- 最终的名图是使用1,745名DPYD野生型患者的数据开发的.
- 年龄,性别和治疗方案的类型被确定为严重毒性的显著预测因素.
- 内部验证显示一致性指数为0.68,表明良好的预测能力.
结论:
- 包含易于获取的参数的诺米图可以预测DPYD野生型患者的严重capecitabine毒性.
- 这种工具可以帮助临床医生管理基于capecitabine的化疗风险.
- 需要进一步的外部和临床验证来确认该模型的实用性.
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