在新的DPYD变种的背景下,可疑的capecitabine诱导致命毒性
Phu Ngone Thet1,2, Taha Khalid3, Rosalind Ganderton4
1Gastroenterology, Portsmouth Hospitals University NHS Trust, Portsmouth, UK phungonethet@gmail.com.
BMJ case reports
|August 31, 2025
概括
一名患者因未诊断的二皮里米丁脱酶 (DPYD) 缺乏症而死于化疗并发症,这突显了目前DPYD基因测试对皮里米丁治疗安全性的局限性.
科学领域:
- 癌症学
- 药物基因组学
- 临床毒理学
背景情况:
- 皮里米丁化疗是治疗各种癌症的基石.
- 甲胺脱酶 (DPYD) 酶的活性对甲胺代谢至关重要.
- 缺乏DPYD可能导致严重的,危及生命的毒性.
研究的目的:
- 在被认为是DPYD缺乏症的患者中报告致命的严重胺毒性病例.
- 突出标准DPYD基因型鉴定在检测所有导致缺陷的变体方面的局限性.
- 强调需要谨慎地注射胺和全面的毒性监测.
主要方法:
- 一位70多岁的男性患者接受辅助化疗.
- 在治疗前对标准DPYD基因型检测结果进行审查.
- 临床观察严重的胃肠道毒性,肠道缺血和患者死亡.
主要成果:
- 患者出现严重的胃肠道毒性,进展为肠道缺血和死亡.
- 在化疗前,标准DPYD基因型检测结果正常.
- 结果表明未被诊断的DPYD缺乏可能是由于未被检测到的变体.
结论:
- 目前的DPYD基因定型可能无法识别所有具有功能意义的DPYD变异.
- 在皮里米丁治疗期间出现意外的严重毒性,需要仔细重新评估和考虑DPYD缺乏.
- 对患者监测和潜在的DPYD缺乏的综合方法对于安全的胺使用至关重要.
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