Fluoropyrimidine Toxicities and DPYD Genotyping: A Clinical Case

Fluoropyrimidines are metabolized mainly by the enzyme dihydropyrimidine dehydrogenase (DPD). Some variants in the coding gene, DPYD, have already been associated with increased toxicity, and their testing is recommended in patients proposed for treatment with these drugs. In this clinical case, a patient without the four variants recommended for testing showed toxicity from the second cycle of capecitabine onwards, requiring hospitalization in the third cycle. Sequencing of the DPYD gene showed the presence of three heterozygous variants which the laboratory interpreted as deleterious to the expression or function of DPD. In the absence of phenotypic testing, the patient stopped treatment, which is also the usual procedure in the case of compound heterozygosity of the variants usually tested. The literature review shows data for and against the role of each variant found in fluoropyrimidine toxicity, but there may be more concrete data in the study of haplotypes with multiple variants and the need to research alterations in other genes to better understand their relationship with toxicity.