Prospective DPYD genotyping to reduce the risk of fluoropyrimidine-induced severe toxicity: Ready for prime time.

5-Fluorouracil (5-FU) and capecitabine (CAP) are among the most frequently prescribed anticancer drugs. They are inactivated in the liver by the enzyme dihydropyrimidine dehydrogenase (DPD). Up to 5% of the population is DPD deficient and these patients have a significantly increased risk of severe and potentially lethal toxicity when treated with regular doses of 5-FU or CAP. DPD is encoded by the gene DPYD and variants in DPYD can lead to a decreased DPD activity. Although prospective DPYD genotyping is a valuable tool to identify patients with DPD deficiency, and thus those at risk for severe and potential life-threatening toxicity, prospective genotyping has not yet been implemented in daily clinical care. Our goal was to present the available evidence in favour of prospective genotyping, including discussion of unjustified worries on cost-effectiveness, and potential underdosing. We conclude that there is convincing evidence to implement prospective DPYD genotyping with an upfront dose adjustment in DPD deficient patients. Immediate benefit in patient care can be expected through decreasing toxicity, while maintaining efficacy.

European journal of cancer (Oxford, England : 1990). 2015 Dec 21 [Epub]

Carin A T C Lunenburg, Linda M Henricks, Henk-Jan Guchelaar, Jesse J Swen, Maarten J Deenen, Jan H M Schellens, Hans Gelderblom

Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands., Division of Clinical Pharmacology, Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands., Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands., Department of Clinical Pharmacy, Catharina Hospital, Eindhoven, The Netherlands., Division of Clinical Pharmacology, Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Division of Pharmacoepidemiology and Clinical Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands., Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: This email address is being protected from spambots. You need JavaScript enabled to view it..