对光皮里米丁抗剂尿氨酸三酸盐的审查
Jack T Thompson1, David M Wood1,2, Paul I Dargan1,2
1Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust, London, UK.
British journal of clinical pharmacology
|October 29, 2024
概括
尿素三酸盐有效地治疗来自5-甲 (5-FU) 化疗的严重毒性. 这种解毒剂在过量服用的情况下显著提高了生存率,使许多患者能够恢复治疗.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
- 临床医学 临床医学
背景情况:
- 甲胺化学疗法,包括5-甲 (5-FU) 和capecitabine,广泛使用,但与20-30%的患者的严重毒性有关.
- 遗传因素,如二皮里米丁脱酶缺乏,有助于毒性,虽然预先查有帮助,但并不能防止所有严重的不良事件.
- 尿素三酸盐于2015年被FDA批准,作为 pyrimidine 过量剂和毒性的解药.
研究的目的:
- 评价尿素三酸盐作为氧胺化学疗法诱导过量和严重毒性的解药的疗效.
- 评估尿素三酸盐对患者生存和在经历严重不良反应后恢复化疗的能力的影响.
- 探索尿素三酸盐在延迟毒性管理方面的潜力及其适用于其他氧胺前药物,如 tegafur.
主要方法:
- 由于对安慰剂控制研究的伦理考虑,III期试验使用了历史对照.
- 分析了用尿素三酸盐治疗的氧胺过量和严重毒性患者的生存数据.
- 审查了病例报告,以评估尿素三酸盐在延迟毒性情景中的疗效.
主要成果:
- 尿素三酸盐显示,氧胺过量剂和严重毒性患者的生存率显著改善,生存率从16%增加到94%.
- 大约34%的用尿素三酸盐治疗的患者能够在30天内恢复化疗.
- 病例报告表明,尿素三酸盐可能对延迟的毒性有效,即使在最后一剂甲胺剂后120-504小时内服用.
结论:
- 尿素三酸是一种高效的解药,用于管理与5-FU和capecitabine化疗相关的过量和严重毒性.
- 该药物提供了显著的生存益处,并促进恢复癌症治疗的患者经历危及生命的不良影响.
- 有证据表明,尿素三酸盐的潜在效用扩展到延迟毒性和可能其他甲胺剂,需要进一步调查.
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