Fluoropyrimidines are the cornerstones of all currently applied regimens for the treatment of patients with cancers of the gastrointestinal tract, breast, head and neck. Dihydropyrimidine dehydrogenase plays a pivotal role in the metabolism of 5-fluorouracil and, as such, a deficiency of dihydropyrimidine dehydrogenase has been recognised as an important risk factor, predisposing patients to develop severe 5-fluorouracil associated toxicity. Screening for dihydropyrimidine dehydrogenase deficiency would not only decrease fluoropyrimidine morbidity and enhance patient quality of life but also potentially reduce costs by avoiding toxicity-related hospitalisations. Genotype and phenotype-based dosing recommendations of fluoropyrimidines propose a dose of 50% of the starting dose followed by an increase in dose in patients experiencing no or clinically tolerable toxicity, to ensure efficacy and a dose decrease in patients who do not tolerate the starting dose, to minimize toxicity.
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