ArticleClinical pharmacology and therapeutics2022
Dihydropyrimidine Dehydrogenase Phenotyping Using Pretreatment Uracil: A Note of Caution Based on a Large Prospective Clinical Study.
Article in Clinical pharmacology and therapeutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 55 citations in OpenAlex.
- Association of DPYD rs4294451, plasma uracil concentration, and sex with 5-fluorouracil exposure in patients with gastrointestinal cancer.Cancer chemotherapy and pharmacology · 2025Article
- Real-world study on fluoropyrimidine-related toxicity outcomes in cancer patients with select DPYD variant alleles that received DPYD genotype-guided dosing.International journal of cancer · 2025Article
- DPYD Genotyping, Fluoropyrimidine Dosage and Toxicity: An Umbrella Review of Systematic Reviews.Pharmaceuticals (Basel, Switzerland) · 2025Review
- A Guide for Implementing DPYD Genotyping for Systemic Fluoropyrimidines into Clinical Practice.Clinical pharmacology and therapeutics · 2025Review
- Adjuvant treatment with Capecitabine in patients who received orthotopic liver transplantation with incidental diagnosis of intrahepatic cholangiocarcinoma. Implications on DPYD polymorphisms assessment: report of two cases and review of the literature.Cancer chemotherapy and pharmacology · 2025Review
- Thymine as potential biomarker to predict 5-FU systemic exposure in patients with gastro-intestinal cancer: a prospective pharmacokinetic study (FUUT-trial).Cancer chemotherapy and pharmacology · 2025Article
- DPYD genotype should be extended to rare variants: report on two cases of phenotype / genotype discrepancy.Cancer chemotherapy and pharmacology · 2025Article
- Plasma clearance of 5-fluorouracil is more influenced by variations in glomerular filtration rate than by uracil concentration.Cancer chemotherapy and pharmacology · 2024Article
- Review
- Strategies for DPYD testing prior to fluoropyrimidine chemotherapy in the US.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2024Article
- Complete DPYD genotyping combined with dihydropyrimidine dehydrogenase phenotyping to prevent fluoropyrimidine toxicity: A retrospective study.Cancer medicine · 2024Article
- Integrating rare genetic variants into DPYD pharmacogenetic testing may help preventing fluoropyrimidine-induced toxicity.The pharmacogenomics journal · 2024Article
- Case report: A case of severe capecitabine toxicity due to confirmed in trans compound heterozygosity of a common and rare DPYD variant.Frontiers in pharmacology · 2024Article
- Article
- Assay performance and stability of uracil and dihydrouracil in clinical practice.Cancer chemotherapy and pharmacology · 2023Article
- Quantitative impact of pre-analytical process on plasma uracil when testing for dihydropyrimidine dehydrogenase deficiency.British journal of clinical pharmacology · 2023Article
- Implementation and clinical benefit of DPYD genotyping in a Danish cancer population.ESMO open · 2023Article
- Implementation of pharmacogenetic testing in oncology:Frontiers in pharmacology · 2023Article
- Ten-year experience with pharmacogenetic testing forFrontiers in pharmacology · 2023Article
- Renal impairment and abnormal liver function tests in pre-therapeutic phenotype-based DPD deficiency screening using uracilemia: a comprehensive population-based study in 1138 patients.Therapeutic advances in medical oncology · 2023Article
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Authors and funding
22 authors at 11 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In clinical practice, 25-30% of the patients treated with fluoropyrimidines experience severe fluoropyrimidine-related toxicity. Extensively clinically validated DPYD genotyping tests are available to identify patients at risk of severe toxicity due to decreased activity of dihydropyrimidine dehydrogenase (DPD), the rate limiting enzyme in fluoropyrimidine metabolism. In April 2020, the European Medicines Agency recommended that, as an alternative for DPYD genotype-based testing for DPD deficiency, also phenotype testing based on pretreatment plasma uracil levels is a suitable method to identify patients with DPD deficiency. Although the evidence for genotype-directed dosing of fluoropyrimidines is substantial, the level of evidence supporting plasma uracil levels to predict DPD activity in clinical practice is limited. Notwithstanding this, uracil-based phenotyping is now used in clinical practice in various countries in Europe. We aimed to determine the value of pretreatment uracil levels in predicting DPD deficiency and severe treatment-related toxicity. To this end, we determined pretreatment uracil levels in 955 patients with cancer, and assessed the correlation with DPD activity in peripheral blood mononuclear cells (PBMCs) and fluoropyrimidine-related severe toxicity. We identified substantial issues concerning the use of pretreatment uracil in clinical practice, including large between-center study differences in measured pretreatment uracil levels, most likely as a result of pre-analytical factors. Importantly, we were not able to correlate pretreatment uracil levels with DPD activity nor were uracil levels predictive of severe treatment-related toxicity. We urge that robust clinical validation should first be performed before pretreatment plasma uracil levels are used in clinical practice as part of a dosing strategy for fluoropyrimidines.
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