Fluorouracil Dosing

The DPYD gene encodes an enzyme that catabolizes pyrimidines and fluoropyrimidines, like capecitabine and fluorouracil. An estimated 1% to 2% of the population has germline pathogenic variants in DPYD, which lead to reduced DPD protein function and an accumulation of pyrimidines and fluoropyrimidines in the body.[9,10] Patients with the DPYD*2A variant who receive fluoropyrimidines may experience severe, life-threatening toxicities that are sometimes fatal. Many other DPYD variants have been identified, with a range of clinical effects.[9-11] Fluoropyrimidine avoidance or a dose reduction of 50% may be recommended based on the patient's DPYD genotype and number of functioning DPYD alleles.[12-14] DPYD genetic testing costs less than $200, but insurance coverage varies due to a lack of national guidelines.[15] In addition, testing may delay therapy by 2 weeks, which would not be advisable in urgent situations. This controversial issue requires further evaluation.[16]