title: 5-Fluorouracil Chemotherapy for Dihydropyrimidine Dehydrogenase-deficient Patients: Potential of the Dose-escalation Method.
abstract: BACKGROUND
  Dihydropyrimidine dehydrogenase (DPD) degrades approximately 85% of administered 5-fluorouracil (5-FU). With a reported high mortality rate, chemotherapy is generally contraindicated for patients with DPD deficiency.
  
  
  METHODS
  Chemotherapy was initiated for a 73-year-old man with DPD deficiency. Capecitabine was administered in incrementally increasing doses, beginning with a single pill while monitoring plasma 5-FU concentration, and neutrophil and platelet counts.
  
  
  RESULTS
  DPD protein level was 2.35 U/mg. After increasing the capecitabine dose to 1,800 mg, oxaliplatin and bevacizumab were added. Subsequent DPD protein measurement showed that the level had increased to approximately 12-fold the one before chemotherapy. Sequencing of all 23 exons of DPYD gene revealed a mutation of guanine to thymine in exon 11 (1156 G>T).
  
  
  CONCLUSIONS
  This is the first report to indicate that DPD activity can be induced. These findings may provide early indications of a new method for chemotherapy for DPD-deficient patients.
authors.affiliation: Department of Gastroenterological Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan yy4160@yahoo.co.jp.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Ogura
authors.affiliation: Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Hiratsuka
authors.affiliation: Department of Gastroenterological Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Aisu
authors.affiliation: Department of Gastroenterological Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: Teppei
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Department of Gastroenterological Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: Daibo
authors.initials: D
authors.lastname: Kojima
authors.affiliation: Department of Gastroenterological Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: Syu
authors.initials: S
authors.lastname: Tanimura
authors.affiliation: Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ogata
authors.affiliation: Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
authors.forename: Shuuji
authors.initials: S
authors.lastname: Hara
authors.affiliation: Department of Internal Medicine, Division of Oncology, Hematology and Infectious Diseases, Fukuoka University, Fukuoka, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Mogi
authors.affiliation: Department of Internal Medicine, Division of Oncology, Hematology and Infectious Diseases, Fukuoka University, Fukuoka, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Takamatsu
authors.affiliation: Department of Internal Medicine, Division of Oncology, Hematology and Infectious Diseases, Fukuoka University, Fukuoka, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tamura
authors.affiliation: Cancer Center, Aichi Medical University, Nagakute, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Mishima
authors.affiliation: Department of Gastroenterological Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Yamashita
mesh_terms: D000368:Aged; D001483:Base Sequence; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005472:Fluorouracil / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000201:enzymology; D008297:Male; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic
chemical_list: D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil
keywords: 5-fluorouracil; DPD; DPYD deficiency; Dihydropyrimidine dehydrogenase; cancer; capecitabine