School of Medicine and Public Health, University of Newcastle, College of Health, Medicine and Wellbeing, Callaghan, New South Wales, Australia.
Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia.
Clin Pharmacol Ther. 2022 Oct;112(4):791-802. doi: 10.1002/cpt.2667. Epub 2022 Jun 12.
Fluoropyrimidines (FP; 5-fluorouracil, capecitabine, and tegafur) are a commonly prescribed class of antimetabolite chemotherapies, used for various solid organ malignancies in over 2 million patients globally per annum. Dihydropyrimidine dehydrogenase (DPD), encoded by the DPYD gene, is the critical enzyme implicated in FP metabolism. DPYD variant genotypes can result in decreased DPD production, leading to the development of severe toxicities resulting in hospitalization, intensive care admission, and even death. Management of toxicity incurs financial burden on both patients and healthcare systems alike. Upfront DPYD genotyping to identify variant carriers allows an opportunity to identify patients who are at high risk to suffer from serious toxicities and allow prospective dose adjustment of FP treatment. This approach has been shown to reduce patient morbidity, as well as improve the cost-effectiveness of managing FP treatment. Upfront DPYD genotyping has been recently endorsed by several countries in Europe and the United Kingdom. This review summarizes current knowledge about DPD deficiency and upfront DPYD genotyping, including clinical and cost-effectiveness outcomes, with the intent of supporting implementation of an upfront DPYD genotyping service with individualized dose-personalization.
氟嘧啶类药物（FP；5-氟尿嘧啶、卡培他滨和替加氟）是一类常用的抗代谢化疗药物，每年在全球超过 200 万患者中用于治疗各种实体器官恶性肿瘤。二氢嘧啶脱氢酶（DPD）由 DPYD 基因编码，是参与 FP 代谢的关键酶。DPYD 变异基因型可导致 DPD 产生减少，从而导致严重毒性的发生，导致住院、重症监护入院，甚至死亡。毒性管理给患者和医疗保健系统都带来了经济负担。通过 DPYD 基因分型进行毒性预测，可以识别出易发生严重毒性的高风险患者，并允许对 FP 治疗进行前瞻性剂量调整。这种方法已被证明可降低患者发病率，同时提高管理 FP 治疗的成本效益。欧洲和英国的几个国家最近都支持进行 DPYD 基因分型。这篇综述总结了目前关于 DPD 缺乏和 DPYD 基因分型的知识，包括临床和成本效益结果，旨在支持实施个体化剂量调整的 DPYD 基因分型服务。
