Back to Journals » Cancer Management and Research » Volume 10

Severe toxicity to capecitabine due to a new variant at a donor splicing site in the dihydropyrimidine dehydrogenase (DPYD) gene

Authors García-González X, López-Tarruella S, García MI, González-Haba E, Blanco C, Salvador-Martin S, Jerez Y, Thomas F, Jarama M, Sanjurjo Sáez M, Martín M, López-Fernández LA

Received 17 May 2018

Accepted for publication 18 June 2018

Published 11 October 2018 Volume 2018:10 Pages 4517—4522

DOI https://doi.org/10.2147/CMAR.S174470

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Dr Kenan Onel


Xandra García-González,1,* Sara López-Tarruella,2,* María Isabel García,1 Eva González-Haba,1 Carolina Blanco,1 Sara Salvador-Martin,1 Yolanda Jerez,2 Fabienne Thomas,3 María Jarama,1 María Sanjurjo Sáez,1 Miguel Martín,2 Luis Andrés López-Fernández1

1Pharmacy Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; 2Medical Oncology Service, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; 3Department of Pharmacology, Institut Claudius-Regaud, CRCT, Université de Toulouse, Inserm, UPS, Toulouse, France

*These authors contributed equally to this work

Abstract: Severe, life-threatening adverse reactions to capecitabine sometimes occur in the treatment of solid tumors. Screening for dihydropyrimidine dehydrogenase (DPYD) deficiency is encouraged before start of treatment, but the genetic variants that are commonly analyzed often fail to explain toxicities seen in clinical practice. Here we describe the case of a 79-year-old Caucasian female with breast cancer who presented with life-threatening, rapidly increasing toxicity after 1 week of treatment with capecitabine and for whom routine genetic DPYD test resulted negative. DPYD exon sequencing found variant c.2242+1G>T at the donor splicing site of exon 19. This variant is responsible for skipping of exon 19 and subsequent generation of a non-functional DPYD enzyme. This variant has not been described previously but was found in three other members of the patient’s family. With this case, we show that exon sequencing of DPYD in patients who experience marked toxicity to fluoropyrimidines and test negative for commonly evaluated variants can prove extremely useful for identifying new genetic variants and better explain adverse reactions causality.

Keywords: pharmacogenetics, adverse drug reaction, fluoropyrimidine, breast cancer

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]