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DPYD evaluation and dose adjustment in patients with gastrointestinal cancer before initiation of fluoropyrimidine-based chemotherapy: One-centre experience
Background
Fluoropyrimidines (FP) are the mainstay treatment of many neoplasms, especially the gastrointestinal (GI) tract cancers. Its metabolism is guaranteed by the enzyme dihydropyrimine dehydrogenase (DPD), which in turn is encoded by the DPYD gene. DPD deficits carry an increased risk of FP toxicity, such as stomatitis, diarrhoea, neutropenia and neurotoxicity, and it affects about 3-9% of the Caucasian population. The aim of this study was to evaluate the prevalence of DPYD gene mutations as well as their therapeutic implications.
Methods
Retrospective observational study, which included all patients with GI cancer eligible for treatment with FP from September 2021 to January 2022, and who underwent genetic testing to assess the mutational status of DPYD. Information was collected on the type and mutational status of DPYD, demographic variables, dose modification, and associated toxicities.
Results
A total of 37 patients were included. Of these, 3 (8%) had DPYD heterozygous mutations, namely one with DPYD*2a heterozygotic mutation and two with heterozygotic mutation of the c.2846A>T allele. Regarding demographic characteristics, 2 patients were male and 1 female. The median age was 49 years (46-71 years). Regarding the type of GI neoplasm, 2 patients had rectal neoplasm and the other one had gastric cancer. The antineoplastic treatment was performed in neoadjuvant context in two patients; in the other one it was performed with palliative intent. All started treatment with 50% dose reduction of FP. In one patient, due to good tolerance, the initial dose was increased by 25%. One patient under CAPOX neoadjuvant treatment for rectal cancer, despite the dose reduction, had grade 4 hematologic toxicity.
Conclusions
Prospective determination of the mutational status of DPYD is important in order to prevent potentially fatal toxicity. Despite this, in some patients this can still occur. In this study, 8% of patients had DPYD mutation which is similar to what was describe in the literature, as well as the impact in terms of toxicity. So, these results substantiate the importance of continuing, in clinical practice, with the determination of DPYD mutation status prior to FP treatment, to prevent potentially fatal toxicity.
Legal entity responsible for the study
The author.
Funding
Has not received any funding.
Disclosures
F. Estevinho: Advisory / Consultancy: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Merck, MSD, Novartis, Pfizer, Sanofi Genzyme Portugal. All other authors have declared no conflicts of interest.
