ReviewClinical pharmacology and therapeutics2021
Individualized Dosing of Fluoropyrimidine-Based Chemotherapy to Prevent Severe Fluoropyrimidine-Related Toxicity: What Are the Options?
Review in Clinical pharmacology and therapeutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- Pharmacogenomic Determinants of Adverse Drug Effects: A Systematic Review and Meta-analysis.In vivo (Athens, Greece)Pooled it
- Dihydropyrimidine Dehydrogenase Genotype-Phenotype Correlations in Plasma and Peripheral Blood Mononuclear Cells.Clinical pharmacology and therapeutics · 2026Article
- 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
- Implementation and feasibility of DPYD-guided fluoropyrimidine use in a gastrointestinal oncology clinic at an academic medical center.Frontiers in oncology · 2026Article
- Identification of a largeFrontiers in pharmacology · 2026Article
- Unrecognized mutations in DPYD* 2 A wild-type rectal cancer patients receiving postoperative 5-FU-based chemotherapy - do they have a clinical impact?Cancer chemotherapy and pharmacology · 2025Article
- Artificial intelligence generated 3D body composition predicts dose modifications in patients undergoing neoadjuvant chemotherapy for rectal cancer.Journal of cancer research and clinical oncology · 2025Article
- Optimizing fluoropyrimidine therapy through dihydropyrimidine dehydrogenase polymorphism testing.World journal of gastrointestinal oncology · 2025Article
- A Guide for Implementing DPYD Genotyping for Systemic Fluoropyrimidines into Clinical Practice.Clinical pharmacology and therapeutics · 2025Review
- Differences inPharmaceuticals (Basel, Switzerland) · 2025Article
- Economic Model of Uridine Triacetate Versus Supportive Care for the Treatment of Patients with Life-Threatening Early-Onset Severe Toxicity.Clinical drug investigation · 2025Article
- DPYD genotype should be extended to rare variants: report on two cases of phenotype / genotype discrepancy.Cancer chemotherapy and pharmacology · 2025Article
- Article
- Article
- Lethal 5-Fluorouracil Toxicity in a Carrier ofJCO precision oncology · 2024Article
- A novel large intragenic DPYD deletion causing dihydropyrimidine dehydrogenase deficiency: a case report.BMC medical genomics · 2024Article
- Integrating rare genetic variants into DPYD pharmacogenetic testing may help preventing fluoropyrimidine-induced toxicity.The pharmacogenomics journal · 2024Article
- Clinical implications of a gain-of-function genetic polymorphism in DPYD (rs4294451) in colorectal cancer patients treated with fluoropyrimidines.Frontiers in pharmacology · 2024Article
- Clinical Implementation of Rare and NovelInternational journal of biological sciences · 2024Review
- Artificial Intelligence-Driven Prediction Revealed CFTR Associated with Therapy Outcome of Breast Cancer: A Feasibility Study.Oncology · 2024Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fluoropyrimidines are widely used in the treatment of several types of solid tumors. Although most often well tolerated, severe toxicity is encountered in ~ 20-30% of the patients. Individualized dosing for these patients can reduce the incidence of severe fluoropyrimidine-related toxicity. However, no consensus has been achieved on which dosing strategy is preferred. The most established strategy for individualized dosing of fluoropyrimidines is upfront genotyping of the DPYD gene. Prospective research has shown that DPYD-guided dose-individualization significantly reduces the incidence of severe toxicity and can be easily applied in routine daily practice. Furthermore, the measurement of the dihydropyrimidine dehydrogenase (DPD) enzyme activity has shown to accurately detect patients with a DPD deficiency. Yet, because this assay is time-consuming and expensive, it is not widely implemented in routine clinical care. Other methods include the measurement of pretreatment endogenous serum uracil concentrations, the uracil/dihydrouracil-ratio, and the 5-fluorouracil (5-FU) degradation rate. These methods have shown mixed results. Next to these methods to detect DPD deficiency, pharmacokinetically guided follow-up of 5-FU could potentially be used as an addition to dosing strategies to further improve the safety of fluoropyrimidines. Furthermore, baseline characteristics, such as sex, age, body composition, and renal function have shown to have a relationship with the development of severe toxicity. Therefore, these baseline characteristics should be considered as a dose-individualization strategy. We present an overview of the current dose-individualization strategies and provide perspectives for a future multiparametric approach.
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