ABSTRACT
5-Fluorouracil and its oral prodrug capecitabine are two of the most frequently prescribed chemotherapeutic drugs for the adjuvant and palliative treatment of patients with cancers of the gastrointestinal tract, breast and head and neck. In principle, pharmacogenetics-guided dosing will enable the identification of patients at risk of developing severe toxicity prior to the start of a fluoropyrimidine-based therapy and adjustment of the initial fluoropyrimidine dose. Several phenotyping procedures have been developed to screen patients for a dihydropyrimidine dehydrogenase (DPD) deficiency, such as measurement of the uracil/dihydrouracil ratio, assessment of the DPD activity in peripheral blood mononuclear cells, and loading studies with uracil. To date, numerous decreased function variants have been described in dihydropyrimidine dehydrogenase gene (DPYD) together with dose recommendations based on the gene activity score. In patients who are heterozygous for a “loss-of-function” mutation in DPYD, a dose reduction of 50% has been recommended.
