ReviewESMO open2021
Issues and limitations of available biomarkers for fluoropyrimidine-based chemotherapy toxicity, a narrative review of the literature.
Review in ESMO open, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- A systematic review and meta-analysis of the impacts of germline pharmacogenomics on severe toxicity and symptom burden in adult patients with cancer.Clinical and translational science · 2024Pooled it
- A rare variant in DPYD c.812delT causes severe adverse events of S-1 in a patient with tongue cancer.Cancer chemotherapy and pharmacology · 2026Article
- Observational
- Quantum Chemical Properties of Fluorouracil/XZnChemistryOpen · 2026Article
- 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
- NK-A 17E-233I: a novel competitive inhibitor of human dihydroorotate dehydrogenase (DHODH) for cancer therapy.Journal of experimental & clinical cancer research : CR · 2025Article
- Phloridzin as a Nutraceutical for Cancer Prevention and Therapy: A Comprehensive Review of Its Mechanisms, Bioavailability Challenges and Future Applications.Food science & nutrition · 2025Review
- Exploring Cancer Patients' and Caregivers' Perspectives and Knowledge Regarding Biomarker Testing in Canada.Current oncology (Toronto, Ont.) · 2025Article
- 5-Fluorouracil Toxicity: Revisiting the Relevance of Pharmacokinetic Parameters.Pharmaceuticals (Basel, Switzerland) · 2025Article
- 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
- Trifluridine- and tipiracil-induced DPD inhibition mimicking DPD deficiency: a case report.Frontiers in oncology · 2025Article
- Thymol as adjuvant in oncology: molecular mechanisms, therapeutic potentials, and prospects for integration in cancer management.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- αvβ3 Integrin and Folate-Targeted pH-Sensitive Liposomes with Dual Ligand Modification for Metastatic Breast Cancer Treatment.Bioengineering (Basel, Switzerland) · 2024Article
- Phenotype versus genotype to optimize cancer dosing in the clinical setting-focus on 5-fluorouracil and tyrosine kinase inhibitors.Pharmacology research & perspectives · 2024Review
- Complete DPYD genotyping combined with dihydropyrimidine dehydrogenase phenotyping to prevent fluoropyrimidine toxicity: A retrospective study.Cancer medicine · 2024Article
- Quantitative impact of pre-analytical process on plasma uracil when testing for dihydropyrimidine dehydrogenase deficiency.British journal of clinical pharmacology · 2023Article
- Implementation of pharmacogenetic testing in oncology:Frontiers in pharmacology · 2023Article
- Case report: 5-Fluorouracil treatment in patient with an important partial DPD deficiency.Frontiers in oncology · 2023Article
- Lipid Nanocarrier-Based Drug Delivery Systems: Therapeutic Advances in the Treatment of Lung Cancer.International journal of nanomedicine · 2023Review
- 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
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fluoropyrimidine-based chemotherapies are widely used to treat gastrointestinal tract, head and neck, and breast carcinomas. Severe toxicities mostly impact rapidly dividing cell lines and can occur due to the partial or complete deficiency in dihydropyrimidine dehydrogenase (DPD) catabolism. Since April 2020, the European Medicines Agency (EMA) recommends DPD testing before any fluoropyrimidine-based treatment. Currently, different assays are used to predict DPD deficiency; the two main approaches consist of either phenotyping the enzyme activity (directly or indirectly) or genotyping the four main deficiency-related polymorphisms associated with 5-fluorouracil (5-FU) toxicity. In this review, we focused on the advantages and limitations of these diagnostic methods: direct phenotyping by evaluation of peripheral mononuclear cell DPD activity (PBMC-DPD activity), indirect phenotyping assessed by uracil levels or UH2/U ratio, and genotyping DPD of four variants directly associated with 5-FU toxicity. The risk of 5-FU toxicity increases with uracil concentration. Having a pyrimidine-related structure, 5-FU is catabolised by the same physiological pathway. By assessing uracil concentration in plasma, indirect phenotyping of DPD is then measured. With this approach, in France, a decreased 5-FU dose is systematically recommended at a uracil concentration of 16 ng/ml, which may lead to chemotherapy under-exposure as uracil concentration is a continuous variable and the association between uracil levels and DPD activity is not clear. We aim herein to describe the different available strategies developed to improve fluoropyrimidine-based chemotherapy safety, how they are implemented in routine clinical practice, and the possible relationship with inefficacy mechanisms.
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What OpenQuestion holds
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.