Screening for dihydropyrimidine dehydrogenase deficiency to decrease the risk of severe toxicities related to fluoropyrimidines (5-fluorouracil or capecitabine) - INAHTA Brief

Each year in France, almost 80,000 new patients receive fluoropyrimidines, a group of anticancer drugs including 5-Fluorouracil [5-FU] and its prodrug capecitabine (Xeloda®), used to treat various types of cancer (mainly digestive, breast and head and neck cancer). Fluoropyrimidines-based chemotherapies   , can cause severe toxicities (incidence at around 20%), and rarely but sometimes lethal toxicity (incidence between 0.1 and 1%). Part of these toxicities may be  related to deficiency in the activity of the main enzyme enabling elimination of 5-FU, called dihydropyrimidine dehydrogenase (DPD). This deficiency can be partial (around 3 to 8% of individuals) or complete (between 0.01 and 0.5% of individuals). Therefore, the summary of product characteristics of fluoropyrimidines includes a contraindication to treatment in patients with complete DPD loss, and the recommendation for dose adjustment and careful monitoring in partially deficient patients.

Beginning 2018, the French agency in charge of medicinal product safety ruled in favour of routine screening for DPD deficiency before treatment with fluoropyrimidine. In the absence of a previously established consensus as to the methods of implementation of the screening (detection of variants of the DPYD gene coding for DPD and/or determination of the activity of the DPD enzyme), the Institut National du Cancer (INCa) [French National Cancer Institute] was approached by the Ministry of Health to draw up recommendations for the said methods. Also, in order to enable reimbursement of the test selected to screen for DPD deficiency for all patients by the French health insurance system, regardless of the laboratory carrying out the test (public or private), its registration on the list of reimbursable medical biology procedures is necessary. This registration decision has to be made by the national health insurance fund, but a prior opinion from the Haute Autorité de Santé (HAS) [French National Authority for Health] is required. For this reason, the HAS decided to refer the matter to itself and to work jointly with the INCa to be able to return an opinion without delay