Department of Medical Oncology, Mater Misericordiae University Hospital, Dublin, Ireland.
School of Medicine, University College Dublin, Dublin, Ireland.
J Oncol Pharm Pract. 2024 Sep;30(6):977-982. doi: 10.1177/10781552231192107. Epub 2023 Aug 9.
Fluorouracil (5FU) and capecitabine are metabolised by dihydropyrimidine dehydrogenase (DPD). Up to 9% of people have low levels of a working DPD enzyme and are at risk of severe toxicity from 5FU/capecitabine. In April 2020, the EMEA recommended patients undergo prospective screening for DPD deficiency before starting treatment, and this was introduced in our hospital.
We retrospectively reviewed records of all patients receiving 5FU/capecitabine in a tertiary Irish cancer centre from May 2020 to April 2021 ( = 197), and those starting first-line treatment in May 2019-April 2020 ( = 97). Our primary outcome was to estimate the prevalence of DPYD variant genes by prospective genotypic screening, with secondary outcomes including variant prevalence by prospective and reactive screening in patients receiving first-line treatment, and 5FU toxicity/tolerability in those with detected variants.
In those treated 2020-2021, cancer subtypes included colorectal ( = 120, 61%), breast ( = 34, 17%), and biliary/pancreatic cancers ( = 21, 11%). Median patient age was 62 (range 25-86 years); 40% ( = 79) of patients were screened overall, with a prospective-screening deficiency prevalence of 6.8% ( = 3 of 44). Three patients had pathogenic DPYD-variants detected by prospective screening and tolerated treatment with 50% up-front dose reduction of 5FU, two had variants of uncertain significance detected by reactive screening.
Other Irish studies estimated prevalence at 11-12%. As the number of variants detected was small, and screening rates were incomplete, our study may have underestimated prevalence.
Approximately 6.8% of Irish patients may carry DPD deficiencies, prospective screening is essential to reduce the risk of life-threatening toxicity in these patients.
氟尿嘧啶（5FU）和卡培他滨通过二氢嘧啶脱氢酶（DPD）代谢。多达 9%的人 DPD 酶活性较低，有发生 5FU/卡培他滨严重毒性的风险。2020 年 4 月，EMEA 建议在开始治疗前对接受 5FU/卡培他滨治疗的患者进行前瞻性 DPD 缺乏筛查，该建议在我院实施。
我们回顾性分析了 2020 年 5 月至 2021 年 4 月在爱尔兰一家三级癌症中心接受 5FU/卡培他滨治疗的所有患者（ = 197 例）和 2019 年 5 月至 2020 年 4 月开始一线治疗的患者（ = 97 例）的记录。主要结局是通过前瞻性基因筛查估计 DPYD 变异基因的流行率，次要结局包括一线治疗患者前瞻性和反应性筛查的变异流行率，以及检测到变异患者的 5FU 毒性/耐受性。
2020 年至 2021 年接受治疗的患者中，癌症亚型包括结直肠癌（ = 120，61%）、乳腺癌（ = 34，17%）和胆道/胰腺肿瘤（ = 21，11%）。中位患者年龄为 62 岁（范围 25-86 岁）；总体上有 40%（ = 79 例）的患者接受了筛查，前瞻性筛查的缺乏率为 6.8%（ = 44 例中有 3 例）。3 例通过前瞻性筛查检测到致病性 DPYD 变异，5FU 初始剂量减少 50%后可耐受治疗，2 例通过反应性筛查检测到意义不明的变异。
其他爱尔兰研究估计患病率为 11-12%。由于检测到的变异数量较少，且筛查率不完全，因此我们的研究可能低估了患病率。
约 6.8%的爱尔兰患者可能存在 DPD 缺乏，前瞻性筛查对于降低这些患者发生危及生命毒性的风险至关重要。
