Background and importance Fluoropyrimidines are antineoplastic drugs used for the treatment of many types of solid tumours. Approximately 80–90% administered is metabolised by the enzyme dihydropyrimidine dehydrogenase (DPYD). Partial or total deficiency of this enzyme is related to severe toxicity and in some cases it can cause the death of the patient.

Aim and objectives The aim of our study was to determine the frequency of these polymorphisms in the DPYD gene in patients treated in our hospital, and to identify those patients with a predisposition to excessive toxicity if they are exposed to fluoropyrimidines.

Material and methods Genetic analysis of the DPYD gene was performed on all patients who started treatment with fluoropyrimidines between September 2017 and April 2020. The variables collected were: age, type of tumour diagnosed and toxicity presented in the first six treatment cycles according to the common terminology criteria for adverse events (CTCAE) classification. Data were obtained from the electronic medical records (Diraya) and the electronic prescription programme (Farmis). The polymorphisms studied were rs3918290, rs55886062, rs67376798 and rs56038477.

Results Genetic analysis was performed on 171 patients. Median age was 71 years. Most of the diagnoses corresponded to colorectal cancer (81%). Patients presented the following adverse events: digestive toxicity in 59% of patients (CTCAE: 1, 2, 3), mucositis 20% (CTCAE: 1, 2), haematological toxicity 17% (CTCAE: 2), hepatotoxicity 6% (CTCAE: 2, 3), neuropathy 16% (CTCAE: 1, 2) and erythrodysaesthesia 10% (CTCAE: 1, 2, 3). 42% of patients required drug withdrawal or dose reduction due to toxicity. Regarding the results of the polymorphisms studied, 95.3% presented a wild-type genotype for the analysed variants. 4.7% of patients presented with some mutated allele (heterozygote): three patients for rs3918290, three patients for rs67376798 and two patients for rs56038477, coinciding with the patients who presented greater toxicity.

Conclusion and relevance The heterozygous patients detected were at risk of developing severe toxicity when they were treated with fluoropyrimidines and they required dose adjustment of these drugs. The use of these pharmacogenetic tools for the determination of polymorphisms of the DPYD gene in routine practice allows us to predict the potentially serious toxicity, favouring the individualised use of these drugs.

Conflict of interest No conflict of interest