5-fluorouracil (5-FU) and its pro-drug capecitabine are widely used anticancer agents. Most 5-FU catabolism is dependent on dihydropyrimidine dehydrogenase (DPD) encoded by the DPYD gene, and DPYD variants that reduce DPD function increase 5-FU toxicity. Most DPD deficient patients are heterozygous and can be treated with reduced 5-FU dosing. We describe a patient with a genotype associated with absent DPD function, and severe and likely fatal toxicity with 5-FU treatment. The patient was treated effectively with alternative systemic therapy. Routine pretreatment DPYD genotyping is recommended by the European Medicines Agency, and guidelines for use of 5-FU in DPD deficient patients are available. However, outside the province of Quebec, routine pretreatment screening for DPD deficiency remains unavailable in Canada. It is likely our patient would have died from 5-FU toxicity under the current standard of care, but instead provides an example of the potential benefit of DPYD screening on patient outcomes.

中文翻译：

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接近小姐或护理标准？接受氟尿嘧啶的癌症患者的 DPYD 筛查

5-氟尿嘧啶 (5-FU) 及其前药卡培他滨是广泛使用的抗癌药物。大多数 5-FU 分解代谢依赖于由 DPYD 基因编码的二氢嘧啶脱氢酶 (DPD)，而降低 DPD 功能的 DPYD 变体会增加 5-FU 的毒性。大多数 DPD 缺陷患者是杂合子，可以减少 5-FU 剂量进行治疗。我们描述了一名患者，其基因型与 DPD 功能缺失相关，5-FU 治疗具有严重且可能致命的毒性。患者接受了替代全身治疗的有效治疗。欧洲药品管理局推荐常规预处理 DPYD 基因分型，并且有在 DPD 缺陷患者中使用 5-FU 的指南。然而，在魁北克省以外，加拿大仍然无法进行 DPD 缺乏症的常规预处理筛查。