Prospective DPYD genotyping to reduce the risk of fluoropyrimidine-induced severe toxicity: Ready for prime time. (February 2016)

• Record Type: Journal Article
• Authors: Lunenburg, Carin A.T.C.; Henricks, Linda M.; Guchelaar, Henk-Jan; Swen, Jesse J.; Deenen, Maarten J.; Schellens, Jan H.M.; Gelderblom, Hans
• Is Part Of: European journal of cancer. Volume 54(2016)
• Page Start: 40
• Page End: 48
• Publication Date: 2016-02
• Subjects: Dihydropyrimidine dehydrogenase -- DPYD -- Fluoropyrimidines -- Capecitabine -- 5-Fluorouracil -- Pharmacogenomics -- Individualised medicine; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2015.11.008
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: 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. Highlights: Genotyping identifies dihydropyrimidine dehydrogenase (DPD) deficient patients, prevents toxicity and is cost-effective. DPD-deficient patients should receive a reduced 5-fluorouracil or capecitabine starting dose. Evidence from an RCT is not likely to be obtained for DPYD genotyping. Implementation of a diagnostic test should not require an RCT per se. Immediate benefit for patients can be expected using DPYD for personalised medicine.