Background and importance Dihydropyrimidine dehydrogenase (DPD) is the first of the enzymes in the fluoropyrimidine metabolic pathway. It is the rate-limiting enzyme in the catabolism of fluoropyrimidine drugs. Patients with partial or total deficiency in DPD activity can not adequately degrade fluoropyrimidines, increasing the risk of serious toxicity.
Aim and objectives To assess the rate of deficiency of the metabolising enzyme DPD in our population and describe the management of these patients in clinical practice.
Material and methods The study was conducted between January 2020 and August 2021. Patients diagnosed with colorectal cancer receiving capecitabine were included. Age, gender, Eastern Cooperative Oncology Group (ECOG), regimen treatments and number of cycles were collected from the electronic clinical history. To determine the variants of DPD, a pharmacogenomics analysis was performed using a real-time polymerase chain reaction (PCR) technique. The polymorphisms studied were rs3918290, rs55886062, rs67376798 and rs56038477. Regarding the management of patients, the doses reduction, adverse events (AE), and withdrawal treatments were recorded.
Results A total of 35 patients in treatment with capecitabine were selected for the analysis of DPD activity. The study population comprised 24 men (68.6%) and 11 women (31.4%). The average age was 60 (27–87) years. ECOG 0–1 was observed in 97.1% of cases. Oxaliplatin plus capecitabine was the initial cancer therapy in 74.3% of patients, and 25.7% were treated with capecitabine in monotherapy. A mutated allele heterozygote was detected in 11.4% of patients: rs67376798 (8.6%) and rs56038477 (2.9%). A 50% dose reduction was prescribed initially according to pharmacogenetics recommendations in DPD deficiency and this dose was maintained throughout the entire treatment. In patients without mutation a dose reduction was required in 22.9%. All patients with DPD mutation and 41.9% without DPD mutation presented AE. The most common AE in this population were gastrointestinal such as nausea (25.7%), constipation (14.3%), diarrhoea (11.4%) and vomiting (11.4%). No withdrawal treatments were registered.
Conclusion and relevance Patients with DPD polymorphisms in our population completed treatment with 50% of the dose. AE were more prevalent in DPD mutation group. Determination of variants of DPD can help avoid serious or fatal EA.
Conflict of interest No conflict of interest
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