title: [Severe toxicity following capecitabine administration because of dihydropyrimidine deshydrogenase (DPD) deficiency].
abstract: Capecitabine is an anticancer agent, prodrug of 5 fluorouracil (5-FU) administered orally and with a narrow therapeutic index. In gastrointestinal cancer, capecitabine is indicated for the treatment of colorectal cancer and metastatic unresectable gastric cancer. The 5-FU is active by incorporation in the biosynthesis of nucleic acids. Inhibition of endogenous synthesis of thymidine is the main way of toxicity of 5-FU. 5-FU is metabolised by the dihydopyrimydine dehydrogenase (DPD). Patients with a DPD deficiency can experience severe toxicity of 5-FU. We report the case of a patient who presented signs of major toxicity justifying hospitalization in intensive care unit 11 days after capecitabine initiation. Investigations showed that he had a DPD deficiency. This case leads to explain the different biological ways to identify patients at risk of developing severe toxicity following capecitabine administration because of DPD deficiency. Is it possible to make a systematic screening before initiation of treatment with 5-FU or prodrug of 5-FU?
authors.affiliation: Département de pharmacie, centre hospitalier de Villefranche-sur-Saône, BP 436, 69655 Villefranche cedex, France. scoursier@ch-villefranche.fr <scoursier@ch-villefranche.fr>
authors.forename: S
authors.initials: S
authors.lastname: Coursier
authors.forename: S
authors.initials: S
authors.lastname: Martelet
authors.forename: A
authors.initials: A
authors.lastname: Guillermet
authors.forename: J
authors.initials: J
authors.lastname: Emptoz
authors.forename: C
authors.initials: C
authors.lastname: Villier
authors.forename: H
authors.initials: H
authors.lastname: Bontemps
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D054067:Dihydropyrimidine Dehydrogenase Deficiency; D017809:Fatal Outcome; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D007362:Intensive Care Units; D008297:Male
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil