Colorectal cancer is the second most common cancer in Europe. Most antineoplastic regimens in first-line treatment involve 5-fluorouracil or oral prodrug capecitabine, combined with other antineoplastic agents such as oxaliplatin or irinotecan. It is well known that 5-fluorouracil and capecitabine are agents that can be toxic in cases of decreased dihydropyrimidine dehydrogenase activity because this enzyme is the main limiting factor in the metabolism of both agents. In this paper, we describe the case of a patient who developed severe toxicity to 5-fluouracil and who had a mutation in the gene encoding the enzyme dihydropyrimidine dehydrogenase.
FerlayJSteliarova-FoucherELortet-TieulentJ. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer2013; 49: 1374–1403.
2.
Van CutsemECervantesANordlingerB. ESMO Guidelines Working Group. Metastatic colorectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol2014; 25(Suppl 3): iii1–9.
van KuilenburgABMeinsmaRZonnenbergBA. Dihydropyrimidinase deficiency and severe 5 fluorouracil toxicity. Clin Cancer Res2003; 9: 4363–4367.
7.
MattisonLKFourieJDesmondRA. Increased prevalence of dihydropyrimidine dehydrogenase deficiency in African-Americans compared with Caucasians. Clin Cancer Res2006; 12: 5491–5495.
SwenJJNijenhuisMde BoerA. Pharmacogenetics: from bench to byte an update of guidelines. Clin Pharmacol Ther2011; 89: 662–673.
10.
Ramos-DíazRGutiérrez-NicolásFNazco-CasariegoGJ. Validation of a fast and low-cost alkaline lysis method for gDNA extraction in a pharmacogenetic context. Cancer Chemother Pharmacol2015; 75: 1095–1098.
11.
CaudleKEThornCFKleinTE. Clinical Pharmacogenetics Implementation Consortium guidelines for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing. Clin Pharmacol Ther2013; 94: 640–645.
12.
RaidaMSchwabeWHäuslerP. Prevalence of a common point mutation in the dihydropyrimidine dehydrogenase (DPD) gene within the 5′-splice donor site of intron 14 in patients with severe 5-fluorouracil (5-FU) related toxicity compared with controls. Clin Cancer Res2001; 7: 2832–2839.
13.
AmstutzUFareseSAebiS. Dihydropyrimidine dehydrogenase gene variation and severe 5-fluorouracil toxicity: a haplotype assessment. Pharmacogenomics2009; 10: 931–944.
SchmollHJVan CutsemESteinA. ESMO Consensus Guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making. Ann Oncol2012; 23: 2479–2516.
