Oncotarget

Clinical Research Papers:

Variants in CDA and ABCB1 are predictors of capecitabine-related adverse reactions in colorectal cancer

Xandra García-González, Lucía Cortejoso, María I. García, Pilar García-Alfonso, Luis Robles, Cristina Grávalos, Eva González-Haba, Pellicer Marta, María Sanjurjo and Luis A. López-Fernández _

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Oncotarget. 2015; 6:6422-6430. https://doi.org/10.18632/oncotarget.3289

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Abstract

Xandra García-González1,*, Lucía Cortejoso1,*, María I. García1, Pilar García-Alfonso2, Luis Robles3, Cristina Grávalos3, Eva González-Haba1, Pellicer Marta1, María Sanjurjo1 and Luis A. López-Fernández1

1 Department of Pharmacy, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain

2 Department of Medical Oncology, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain

3 Department of Medical Oncology, Hospital Universitario Doce de Octubre, Instituto de Investigación Sanitaria Doce de Octubre, Madrid, Spain

* These authors contributed equally to the manuscript

Correspondence:

Luis A. López-Fernández, email:

Keywords: Flouropyrimidine, toxicity, chemotherapy, genetics

Received: October 14, 2014 Accepted: January 02, 2015 Published: January 21, 2015

Abstract

Adverse reactions to capecitabine-based chemotherapy limit full administration of cytotoxic agents. Likewise, genetic variations associated with capecitabine-related adverse reactions are associated with controversial results and a low predictive value. Thus, more evidence on the role of these variations is needed. We evaluated the association between nine polymorphisms in MTHFR, CDA, TYMS, ABCB1, and ENOSF1 and adverse reactions, dose reductions, treatment delays, and overall toxicity in 239 colorectal cancer patients treated with capecitabine-based regimens. The ABCB1*1 haplotype was associated with a high risk of delay in administration or reduction in the dose of capecitabine, diarrhea, and overall toxicity. CDA rs2072671 A was associated with a high risk of overall toxicity. TYMS rs45445694 was associated with a high risk of delay in administration or reduction in the dose of capecitabine, HFS >1 and HFS >2. Finally, ENOSF1 rs2612091 was associated with HFS >1, but was a poorer predictor than TYMS rs45445694. A score based on ABCB1-CDA polymorphisms efficiently predicts patients at high risk of severe overall toxicity (PPV, 54%; sensitivity, 43%) in colorectal cancer patients treated with regimens containing capecitabine. Polymorphisms in ABCB1, CDA, ENOSF1,and TYMS could help to predict specific and overall severe adverse reactions to capecitabine.


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