Actuality of pharmacogenetic testing application for 5-fluorouracil toxity prediction
Abstract
Objective of this study was to assess the association of G735A mutation in the DPYD gene detected by PCR in patients who are prescribed 5-fluorouracil or capecitabine with the development of nephrotoxicity, hepatotoxicity, and hematotoxicity. Hematotoxicity was assessed using a general blood test. Assessment of hepatotoxicity and nephrotoxicity was carried out according to the general biochemical analysis of blood (total bilirubin, AST, ALT, urea, creatinine). All indicators were evaluated before the start of therapy and after completion of the course of therapy. At this stage of the study, the genes associated with the toxicity of fluorouracil and capecitabine were not found among the examined patients, and there were also no critical manifestations of toxicity after using these drugs according to clinical and laboratory tests. This study is considered as a pilot. However, given the low prevalence of the frequency of occurrence of mutant alleles, using of this type of testing in the region may be inappropriate.
About the Authors
G. G. Ketova
South-Urals State Medical University
Russian Federation
Russian Federation
Chelyabinsk
V. O. Barysheva
South-Urals State Medical University Clinic
Russian Federation
Russian Federation
Chelyabinsk
M. S. Salnikov
Railway clinical hospital
Russian Federation
Russian Federation
Chelyabinsk
E. E. Dvorchik
South-Urals State Medical University Clinic
Russian Federation
Russian Federation
Chelyabinsk
S. V. Kvyatkovskaya
South-Urals State Medical University Clinic
Russian Federation
Russian Federation
Chelyabinsk
S. L. Kremlev
South-Urals State Medical University Clinic
Russian Federation
Russian Federation
Chelyabinsk
References
1. Моисеев А. А. Роль фармакогенетики в индивидуализации противоопухолевой химиотерапии // Фарматека. 2013. № 8. С. 15–20.
2. Meulendijks D., Henricks L. M., Sonke G. S. et al. Clinical relevance of DPYD variants c.1679T>G, c.1236G>A/HapB3, and c.1601G>A as predictors of severe fluoropyrimidine-associated toxicity: a systematic review and meta-analysis of individual patient data // Lancet Oncol. 2015. Vol. 16, № 16. P. 1639–1650.
3. Bray F., Ferlay J., Soerjomataram I. et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries // CA Cancer J. Clin. 2018. Vol. 68, № 6. P. 394–424.
4. Fleming R. A., Milano G., Thyss A. et al. Correlation between dihydropyrimidine dehydrogenase activity in peripheral mononuclear cells and systemic clearance of fluorouracil in cancer patients // Cancer Res. 1992. Vol. 52, № 10. P. 2899–2902.
5. Deenen M. J., Tol J., Burylo A. M. et al. Relationship between single nucleotide polymorphisms and haplotypes in DPYD and toxicity and efficacy of capecitabine in advanced colorectal cancer // Clin. Cancer Res. 2011. Vol. 17, № 10. P. 3455–3468.
6. Caudle K. E., Klein T. E., Hoffman J. M. et al. Incorporation of pharmacogenomics into routine clinical practice: the Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline development process // Curr. Drug Metab. 2014. Vol. 15, № 2. P. 209–217.
7. Сычев Д. А. Фармакогенетическое тестирование: клиническая интерпретация результатов. М., 2011. 89 с.
8. Amstutz U., Henricks L. M., Offer S. M. et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing: 2017 Update // Clin. Pharmacol. Ther. 2018. Vol. 103, № 2. P. 210–216.
Review
For citations:
Ketova G.G., Barysheva V.O., Salnikov M.S., Dvorchik E.E., Kvyatkovskaya S.V., Kremlev S.L. Actuality of pharmacogenetic testing application for 5-fluorouracil toxity prediction. Title in english. 2020;15(4):10-13. (In Russ.)
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