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Background and Importance Fluoropyrimidines are used in cancer treatment but show variability in tolerance, with one of the main causes being the deficiency of the enzyme dihydropyrimidine dehydrogenase (DPD), encoded by the dihydropyrimidine dehydrogenase (DPYD) gene, responsible for the drug’s metabolism. This deficiency can reduce drug elimination and increase toxicity risk.Genetic testing before treatment allows dose individualisation, optimising efficacy and reducing toxicity.Aim and Objectives The study aimed to determine the prevalence and types of DPYD variants in patients at our centre and to analyse how initial doses were managed and adjusted based on tolerance.Material and Methods An observational, retrospective, descriptive study included patients tested for DPYD gene variants before treatment (May 2021–December 2024). A 50% dose reduction is recommended for heterozygous variants 2A and 13, 75% for other heterozygous variants, and treatment is contraindicated for homozygous 2A and 13 variants.Frequency distribution was used for qualitative variables and prevalence measures for quantitative variables.Results A total of 816 requests were made; 98.4% (803) were performed. Determinations were done by an external laboratory until November 2021, then began to be done at our centre.95.1% (764) of patients showed no variants, while 4.9% (39) had variants: DPYDIVS10 in 51.3% (20), DPYDD949V in 23.1% (9), DPYD2A in 20.5% (8), and DPYD13 in 2.6% (1) and one homozygous variant DPYD*D949V in 2.6% (1).Among these patients, 48.7% (19) started fluoropyrimidines: 52.6% (10) started with capecitabine, 26.3% (five) combined with oxaliplatin, 15.8% (three) started 5-fluorouracil combined with oxaliplatin, and 5.3% (one) in combination with oxaliplatin and irinotecan.89.5% (17) patients started with a reduced dose, 23.5% (four) developed diarrhoea, one also neutropenia, although dose reductions were not necessary. Among the patients on treatment, 79,0% (15) had a progressive dose increase, and 46.7% (seven) reached a dose of 70-85%.After escalation, 53.3% (eight) developed gastrointestinal toxicity, hand-foot syndrome, or mucositis, requiring dose reduction in two and discontinuation in three.The prevalence of variants associated with partial reduction in DPYD activity was approximately 5%, the most common being the DPYDIVS10 variant.Conclusion and Relevance DPYD screening effectively identified patients at risk of fluoropyrimidine toxicity, allowing individualised dosing. Initiation with reduced doses was well tolerated, supporting dose escalation. The observed prevalence aligns with literature. This study highlights the importance of pharmacogenetic testing in improving efficacy and safety of fluoropyrimidine treatment.Conflict of Interest No conflict of interest