Capecitabine-induced hand-foot syndrome: A pharmacogenetic study beyond DPYD.

Autor: de With M; Dep. of Medical Oncology, Erasmus MC Cancer Institute, Dr Molewaterplein 40, 3015 GD Rotterdam, the Netherlands; Dep. of Clinical Chemistry, Erasmus University Medical Center, Dr Molewaterplein 40, 3015 GD Rotterdam, the Netherlands., van Doorn L; Dep. of Medical Oncology, Erasmus MC Cancer Institute, Dr Molewaterplein 40, 3015 GD Rotterdam, the Netherlands., Maasland DC; Dep. of Medical Oncology, Erasmus MC Cancer Institute, Dr Molewaterplein 40, 3015 GD Rotterdam, the Netherlands., Mulder TAM; Dep. of Clinical Chemistry, Erasmus University Medical Center, Dr Molewaterplein 40, 3015 GD Rotterdam, the Netherlands., Oomen-de Hoop E; Dep. of Medical Oncology, Erasmus MC Cancer Institute, Dr Molewaterplein 40, 3015 GD Rotterdam, the Netherlands., Mostert B; Dep. of Medical Oncology, Erasmus MC Cancer Institute, Dr Molewaterplein 40, 3015 GD Rotterdam, the Netherlands., Homs MYV; Dep. of Medical Oncology, Erasmus MC Cancer Institute, Dr Molewaterplein 40, 3015 GD Rotterdam, the Netherlands., El Bouazzaoui S; Dep. of Clinical Chemistry, Erasmus University Medical Center, Dr Molewaterplein 40, 3015 GD Rotterdam, the Netherlands., Mathijssen RHJ; Dep. of Medical Oncology, Erasmus MC Cancer Institute, Dr Molewaterplein 40, 3015 GD Rotterdam, the Netherlands., van Schaik RHN; Dep. of Clinical Chemistry, Erasmus University Medical Center, Dr Molewaterplein 40, 3015 GD Rotterdam, the Netherlands., Bins S; Dep. of Medical Oncology, Erasmus MC Cancer Institute, Dr Molewaterplein 40, 3015 GD Rotterdam, the Netherlands. Electronic address: s.bins@erasmusmc.nl.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2023 Mar; Vol. 159, pp. 114232. Date of Electronic Publication: 2023 Jan 09.
DOI: 10.1016/j.biopha.2023.114232
Abstrakt: Aim of the Study: Occurrence of hand-foot syndrome (HFS) during capecitabine treatment often results in treatment interruptions (26 %) or treatment discontinuation (17 %), and can severely decrease quality of life. In this study, we investigated whether single nucleotide polymorphisms (SNPs) in genes involved in capecitabine metabolism - other than DPYD - are associated with an increased risk for capecitabine-induced HFS.
Methods: Patients treated with capecitabine according to standard of care were enrolled after providing written informed consent for genotyping purposes. Prospectively collected blood samples were used to extract genomic DNA, which was subsequently genotyped for SNPs in CES1, CES2 and CDA. SNPs and clinical baseline factors that were univariably associated with HFS with P ≤ 0.10, were tested in a multivariable model using logistic regression.
Results: Of the 446 patients eligible for analysis, 146 (32.7 %) developed HFS, of whom 77 patients (17.3 %) experienced HFS ≥ grade 2. In the multivariable model, CES1 1165-33 C>A (rs2244613, minor allele frequency 19 %) and CDA 266 + 242 A>G (rs10916825, minor allele frequency 35 %) variant allele carriers were at higher risk of HFS ≥ grade 2 (OR 1.888; 95 %CI 1.075-3.315; P = 0.027 and OR 1.865; 95 %CI 1.087-3.200; P = 0.024, respectively).
Conclusions: We showed that CES1 1165-33 C>A and CDA 266 + 242 A>G are significantly associated with HFS grade 2 and grade 3 in patients treated with capecitabine. Prospective studies should assess whether this increased risk can be mitigated in carriers of these SNPs, when pre-emptive genotyping is being followed by dose adjustment or by alternative treatment by a fluoropyrimidine that is not substrate to CES1, such as S1.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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