Observational studyPloS one2017
New advances in DPYD genotype and risk of severe toxicity under capecitabine.
Observational study in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00953537 (Multicentric Pilot Study of Dihydropyrimidine Dehydrogenase), which is not on this map. Cited by 47 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Multicentric Pilot Study of Dihydropyrimidine Dehydrogenase (DPD) Deficiency for Predicting Capecitabine Toxicity in Breast Cancer Patients
Who cites it
47 citing papers in PubMed, 2 syntheses or guidelines pooled it, 102 citations in OpenAlex.
- Pooled it
- Dihydropyrimidine dehydrogenase gene variants for predicting grade 4-5 fluoropyrimidine-induced toxicity: FUSAFE individual patient data meta-analysis.British journal of cancer · 2024Pooled it
- The Impact of Upfront DihydroPyrimidine Dehydrogenase (DPD) Testing on the Therapeutic Management of Patients Scheduled for 5-FU.Cancer medicine · 2026Observational
- DPD Ultra-Rapid Metabolizer Status and Efficacy of 5-Fluorouracil Treatment: A Real-World Study.Fundamental & clinical pharmacology · 2025Article
- DPYD Genotyping, Fluoropyrimidine Dosage and Toxicity: An Umbrella Review of Systematic Reviews.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Pharmacogenomics in Solid Tumors: A Comprehensive Review of Genetic Variability and Its Clinical Implications.Cancers · 2025Review
- Economic Model of Uridine Triacetate Versus Supportive Care for the Treatment of Patients with Life-Threatening Early-Onset Severe Toxicity.Clinical drug investigation · 2025Article
- 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
- Are the Common Genetic 3'UTR Variants in ADME Genes Playing a Role in Tolerance of Breast Cancer Chemotherapy?International journal of molecular sciences · 2024Article
- Review
- Complete DPYD genotyping combined with dihydropyrimidine dehydrogenase phenotyping to prevent fluoropyrimidine toxicity: A retrospective study.Cancer medicine · 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
- Clinical Implementation of Rare and NovelInternational journal of biological sciences · 2024Review
- Article
- Awareness and attitudes of oncology specialists toward dihydropyrimidine dehydrogenase testing in Saudi Arabia.Cancer reports (Hoboken, N.J.) · 2023Article
- Pharmacogenomic-guided dosing of fluoropyrimidines beyondFrontiers in pharmacology · 2023Review
- Can immunotherapy reinforce chemotherapy efficacy? a new perspective on colorectal cancer treatment.Frontiers in immunology · 2023Review
- DPYD genotyping and dihydropyrimidine dehydrogenase (DPD) phenotyping in clinical oncology. A clinically focused minireview.Basic & clinical pharmacology & toxicology · 2022Review
- Dihydropyrimidine Dehydrogenase Phenotyping Using Pretreatment Uracil: A Note of Caution Based on a Large Prospective Clinical Study.Clinical pharmacology and therapeutics · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
33 authors at 16 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDeficiency in dihydropyrimidine dehydrogenase (DPD) enzyme is the main cause of severe and lethal fluoropyrimidine-related toxicity. Various approaches have been developed for DPD-deficiency screening, including DPYD genotyping and phenotyping. The goal of this prospective observational study was to perform exhaustive exome DPYD sequencing and to examine relationships between DPYD variants and toxicity in advanced breast cancer patients receiving capecitabine.
methodsTwo-hundred forty-three patients were analysed (88.5% capecitabine monotherapy). Grade 3 and grade 4 capecitabine-related digestive and/or neurologic and/or hemato-toxicities were observed in 10.3% and 2.1% of patients, respectively. DPYD exome, along with flanking intronic regions 3'UTR and 5'UTR, were sequenced on MiSeq Illumina. DPD phenotype was assessed by pre-treatment plasma uracil (U) and dihydrouracil (UH2) measurement.
resultsAmong the 48 SNPs identified, 19 were located in coding regions, including 3 novel variations, each observed in a single patient (among which, F100L and A26T, both pathogenic in silico). Combined analysis of deleterious variants *2A, I560S (*13) and D949V showed significant association with grade 3-4 toxicity (sensitivity 16.7%, positive predictive value (PPV) 71.4%, relative risk (RR) 6.7, p<0.001) but not with grade 4 toxicity. Considering additional deleterious coding variants D342G, S492L, R592W and F100L increased the sensitivity to 26.7% for grade 3-4 toxicity (PPV 72.7%, RR 7.6, p<0.001), and was significantly associated with grade 4 toxicity (sensitivity 60%, PPV 27.3%, RR 31.4, p = 0.001), suggesting the clinical relevance of extended targeted DPYD genotyping. As compared to extended genotype, combining genotyping (7 variants) and phenotyping (U>16 ng/ml) did not substantially increase the sensitivity, while impairing PPV and RR.
conclusionsExploring an extended set of deleterious DPYD variants improves the performance of DPYD genotyping for predicting both grade 3-4 and grade 4 toxicities (digestive and/or neurologic and/or hematotoxicities) related to capecitabine, as compared to conventional genotyping restricted to consensual variants *2A, *13 and D949V.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.