Sistema de Salut de Catalunya
Otero-Torres, Sara
Rodríguez-Mauriz, Rosa
Fort Casamartina, Eduard
Clopés-Estela, Ana
Soler-Rotllant, Francesc
Fontanals Martínez, Sandra
Montero Pérez, Olalla
[Otero-Torres S, Rodríguez-Mauriz R, Fort-Casamartina E, Soler-Rotllant F, Montero-Pérez O] Servei de Farmàcia, Institut Català d’Oncologia (ICO), Hospital Duran i Reynals, L’Hospitalet de Llobregat, Spain. [Clopés-Estela A] Servei Català de la Salut (CatSalut), Departament de Salut, Generalitat de Catalunya´, Barcelona, Spain. Facultat de Ciències de la Salut, Blanquerna Universitat Ramon, Barcelona, Spain. Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), Facultat de Medicina, Universitat de Barcelona (UB), L’Hospitalet de Llobregat, Spain. [Fontanals-Martínez S] Servei de Farmàcia, Institut Català d’Oncologia (ICO), Hospital Duran i Reynals, L’Hospitalet de Llobregat, Spain. Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), Facultat de Medicina, Universitat de Barcelona (UB), L’Hospitalet de Llobregat, Spain
Departament de Salut
2025-07-03T11:23:08Z
2025-07-03T11:23:08Z
2025-05-15
Genotipat del DPYD; Fluoropirimidines; Toxicitat
DPYD genotyping; Fluoropyrimidines; Toxicity
Genotipado de DPYD; Fluoropirimidinas; Toxicidad
Fluoropyrimidines are widely used chemotherapeutic agents in various solid tumors. Germline variants in the DPYD gene, which encodes the enzyme dihydropyrimidine dehydrogenase (DPD), are known to impair drug metabolism and increase the risk of severe toxicity. This umbrella review aims to synthesize the current evidence from systematic reviews on the association between DPYD variants and fluoropyrimidine-induced toxicity. Methods: A comprehensive search was conducted in PubMed, Web of Science, Scopus, and the Cochrane Library from inception to 2023, including gray literature. Systematic reviews assessing fluoropyrimidine toxicity in oncologic patients with DPYD variants were included. Study quality was assessed using the AMSTAR-2 tool. Registration number in PROSPERO: CRD42023401226. Results: Two independent investigators performed the study selection, quality assessment, and data collection. Eight systematic reviews met the inclusion criteria. Methodological confidence was rated as critically low in six, low in one, and medium in another one. The reviews included 125 primary studies, most of them focused on four key DPYD variants (DPYD2*A, DPYD*13, c.2846A>T, and HapB3), all of which showed consistent associations with an increased risk of severe toxicity. Rare variants such as DPYD*4, *5, and *6 were also examined, though evidence remains limited. Pharmacogenetics-guided dosing of fluoropyrimidines significantly reduced toxicity rates in several studies. The integration of DPYD genotyping with phenotyping approaches faces limitations; these tests should complement rather than replace genotyping information. Conclusions: This umbrella review confirms the clinical relevance of DPYD genotyping to predict and mitigate fluoropyrimidine toxicity. Incorporating genotyping into clinical practice, potentially alongside phenotyping and therapeutic drug monitoring, may enhance patient safety and treatment efficacy.
English
Medicaments - Ús; CHEMICALS AND DRUGS::Enzymes and Coenzymes::Enzymes::Oxidoreductases::Oxidoreductases Acting on CH-CH Group Donors::Dihydrouracil Dehydrogenase (NADP); CHEMICALS AND DRUGS::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Pyrimidines::Pyrimidinones::Uracil::Fluorouracil; Other subheadings::Other subheadings::Other subheadings::/adverse effects; COMPUESTOS QUÍMICOS Y DROGAS::enzimas y coenzimas::enzimas::oxidorreductasas::oxidorreductasas que actúan sobre donantes de grupos CH-CH::dihidrouracilo deshidrogenasa (NADP); Fluorouracilo; Otros calificadores::Otros calificadores::Otros calificadores::/efectos adversos
MDPI
Pharmaceuticals (Basel, Switzerland);18(5)
https://www.doi.org/10.3390/ph18050727
Attribution-NonCommercial 4.0 International
https://creativecommons.org/licenses/by/4.0/
