Dihydropyrimidine Dehydrogenase Deficiency: To Screen or Not to Screen?

Abstract

5-fluorouracil (5-FU) and its prodrug capecitabine are frequently prescribed in oncology. While usually well tolerated, toxicity can be severe, and even life-threatening. A dihydropyrimidine dehydrogenase (DPD) deficiency can cause severe toxicity. Current testing for DPD deficiency does not meet the criteria for a routine screening test prior to 5-FU therapy. A case study of a fatality secondary to capecitabine toxicity is reviewed and literature is examined regarding general screening for DPD deficiency.

Abnormal Dihydropyrimidine Dehydrogenase Activity as an Indicator of Potential 5-Fluorouracil Linked Cardiotoxicity in Colorectal Cancer Patients: Are Toxic Events Inevitable?

“…When heterozygote, the inactivation is partial and decreased by 50% [ 37 ]. Other DPYD mutated variants observed to have high chances of toxic adverse reactions linked to fluoropyrimidines are c.1679T>G and c.2846A>T [ 38 ]. Some centers implement a protocol based on the screening for these variants associated with the DPYD before starting fluoropyrimidine therapy and eventually adjusting the doses of the medication if these variants are present [ 7 ].…”

“…Besides genotyping, another technique that can permit the identification of DPD deficiency is evaluating its action in the peripheral mononuclear cell (PBMC), which is the phenotypical expression of the enzyme [ 38 ]. Because many variants of the DPYD gene are not associated with altering the enzyme activity, using one method alone in assessing patients might prove insufficient; applying both genotyping and phenotype variations has been described in studies [ 39 ].…”