DPD deficiency in an Irish oncology centre: Prevalence and clinical implications.

Introduction: 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.
Methods: We retrospectively reviewed records of all patients receiving 5FU/capecitabine in a tertiary Irish cancer centre from May 2020 to April 2021 ( n  = 197), and those starting first-line treatment in May 2019-April 2020 ( n  = 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.
Results: In those treated 2020-2021, cancer subtypes included colorectal ( n  = 120, 61%), breast ( n  = 34, 17%), and biliary/pancreatic cancers ( n  = 21, 11%). Median patient age was 62 (range 25-86 years); 40% ( n  = 79) of patients were screened overall, with a prospective-screening deficiency prevalence of 6.8% ( n  = 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.
Discussion: 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.
Conclusions: 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.
Competing Interests: Authors contributionRK designed the study, analysed the data and wrote the manuscript, TM, AAlF and AC collected data and proofread the manuscript, CM assisted with data analysis and manuscript editing, JmC was the principal investigator, responsible for study oversight and manuscript editing and approval. All authors reviewed and approved the final version of the manuscript. Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.