Determinants of the interindividual variability in serum cytidine deaminase activity of patients with solid tumours.
Aged
Antimetabolites, Antineoplastic
/ adverse effects
Biological Variation, Population
Biomarkers, Tumor
/ blood
Cytidine Deaminase
/ blood
Deoxycytidine
/ adverse effects
Drug Monitoring
/ methods
Female
Humans
Inflammation
/ blood
Male
Malnutrition
/ blood
Middle Aged
Neutrophils
Nutritional Status
Pancreatic Neoplasms
/ blood
Pharmacogenomic Variants
Polymorphism, Single Nucleotide
Prospective Studies
Gemcitabine
cytidine deaminase
gemcitabine
genotype
interindividual variability
nucleoside analogues
Journal
British journal of clinical pharmacology
ISSN: 1365-2125
Titre abrégé: Br J Clin Pharmacol
Pays: England
ID NLM: 7503323
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
12
06
2018
revised:
23
10
2018
accepted:
14
12
2018
pubmed:
1
2
2019
medline:
14
4
2020
entrez:
1
2
2019
Statut:
ppublish
Résumé
Cytidine deaminase (CDA) activity in cancer patients' serum has been proposed as a predictive biomarker for efficacy and toxicity of nucleoside analogues. However, discrepant results about its predictive value have been reported due to the high interindividual variability in CDA activity. This study aimed at identifying determinants of this interindividual variability. From December 2014 to November 2015, 183 patients were prospectively included. Serum CDA activity, biological and clinical characteristics as well as five common single nucleotide polymorphisms (SNPs) in the CDA gene (c.-451C > T, c.-92A > G, c.-33_-31delC, c.79A > C, c.435 T > C) were analysed. Associations between clinical characteristics, pharmacogenetic variants and CDA activity were univariately tested. P < 0.1-candidate variables were analysed through a multivariate analysis. The association between CDA activity and toxicity was assessed for the 56 gemcitabine-treated patients. Intraindividual variability in CDA activity was explored in six pancreatic cancer patients treated with gemcitabine. Median CDA activity was 3.97 U mg These results suggest that neutrophil count and malnutrition should be considered for the interpretation of pretherapeutic CDA activity.
Identifiants
pubmed: 30701582
doi: 10.1111/bcp.13849
pmc: PMC6533495
doi:
Substances chimiques
Antimetabolites, Antineoplastic
0
Biomarkers, Tumor
0
Deoxycytidine
0W860991D6
Cytidine Deaminase
EC 3.5.4.5
Gemcitabine
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1227-1238Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2018 The British Pharmacological Society.
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