ArticleFundamental & clinical pharmacology2025
DPD Ultra-Rapid Metabolizer Status and Efficacy of 5-Fluorouracil Treatment: A Real-World Study.
Article in Fundamental & clinical pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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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.
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Who cites it
5 citing papers in PubMed.
- The Impact of Upfront DihydroPyrimidine Dehydrogenase (DPD) Testing on the Therapeutic Management of Patients Scheduled for 5-FU.Cancer medicine · 2026Observational
- Recent Advances and Future Directions in 5-Fluorouracil Drug Delivery: A Comprehensive Review.Current topics in medicinal chemistry · 2026Review
- Association of DPYD rs4294451, plasma uracil concentration, and sex with 5-fluorouracil exposure in patients with gastrointestinal cancer.Cancer chemotherapy and pharmacology · 2025Article
- Reply to: Dihydropyrimidine Dehydrogenase Enzyme-Guided Dosing of 5-Fluorouracil: Prioritizing Precision Over Dose Reduction.JCO precision oncology · 2025Article
- DPD Ultra-Rapid Metabolizer Status and Efficacy of 5-Fluorouracil Treatment: A Real-World Study.Fundamental & clinical pharmacology · 2025Article
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAnticancer drug 5FU is extensively metabolized by dihydropyrimidine dehydrogenase (DPD), an enzyme with high interindividual variability. Poor metabolizer (PM, i.e., DPD deficient) patients are at risk of life-threatening toxicities. Whether ultra-rapid metabolizer (UM) status could conversely compromise 5FU efficacy remains to be investigated.
methodsIn this real-world study, 352 adult patients treated with a 5FU-containing regimen were screened. Patients were classified as normal (extensive metabolizer, EM), PM, or UM on DPD function based upon baseline plasma uracil monitoring. The impact of DPD status on efficacy and safety endpoints was investigated.
resultsPatients were categorized on DPD as UM (11.9%), EM (75.9%), and PM (12.2%). The response rate was 54.5%, with median PFS and OS of 13.9 and 19 months, respectively. PM patients were treated with an average 13% lower 5FU starting dose. There was no statistical difference in efficacy between UM and other patients. Severe toxicities were observed in less than 5% of patients, an incidence significantly lower than commonly reported with 5FU-containing regimen and was comparable between UM, EM, and PM patients. Our observations suggest that UM status is not associated with the lack of efficacy of 5FU. In addition, upfront DPD testing with adaptive dosing helps to reduce the incidence of severe toxicities, as PM patients on reduced doses did not have more severe toxicities than other patients treated with standard doses, while exhibiting similar efficacy in terms of response rate and survival.
conclusionWhen upfront DPD screening with adaptive dosing is performed, no difference is observed between UM, EM, and PM patients in terms of efficacy and safety.
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