title: UDP-glucuronosyltransferase (UGT) 1A1*28 polymorphism-directed phase II study of irinotecan with 5'-deoxy-5-fluorouridine (5'-DFUR) for metastatic colorectal cancer.
abstract: OBJECTIVE
  We performed a phase II study of irinotecan with 5'-deoxy-5-fluorouridine (5'-DFUR) for metastatic colorectal cancer based on UDP-glucuronosyltransferase (UGT) 1A1 polymorphism.
  
  
  METHODS
  A total of 28 patients were enrolled. The dose of irinotecan was 150 mg/m(2) for patients with the *1/*1 wild-type genotype, and 70 mg/m(2) for those with the *1/*28 mutated genotype. The primary end-point was the response rate (RR); secondary end-points were safety, time to treatment failure (TTF), and overall survival (OS).
  
  
  RESULTS
  In 28 patients total, genotype was wild-type in 22 and mutated in six. The RR was *1/*1 (22.7%; wild-type) vs. *1/*28 (16.7%; mutated); the median TTF was 5 months vs. 4.5 months, and the median OS was 13 months vs. 17.5 months, respectively. None of these differences were significant. Toxicities of grade 3 or higher were neutropenia (9.0% vs. 0%, respectively) and diarrhea (13.6% vs. 0%, respectively).
  
  
  CONCLUSIONS
  This genotype-oriented therapy was effective and safe, and thus appears useful for patients who have complications or advanced age.
authors.affiliation: Department of Digestive Surgery and Surgical Oncology (Surgery II), Yamaguchi University Graduate School of Medicine,1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan. 2geka-1@yamaguchi-u.ac.jp
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Kanekiyo
authors.forename: Shoichi
authors.initials: S
authors.lastname: Hazama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kondo
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nagashima
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Eto
authors.forename: Shin
authors.initials: S
authors.lastname: Yoshida
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Shimizu
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Araki
authors.forename: Tatsuhito
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Uchiyama
authors.forename: Shigefumi
authors.initials: S
authors.lastname: Yoshino
authors.forename: Naoko
authors.initials: N
authors.lastname: Okayama
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hinoda
authors.forename: Masaaki
authors.initials: M
authors.lastname: Oka
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D005260:Female; D005467:Floxuridine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011110:Polymorphism, Genetic; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D000099148:UGT1A1 Enzyme
chemical_list: D000970:Antineoplastic Agents; D002166:Camptothecin; D005467:Floxuridine; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D000099148:UGT1A1 Enzyme; C025034:doxifluridine
keywords: 5’-deoxy-5-fluorouridine (5’-DFUR); Metastatic colorectal cancer; UDP-glucuronosyltransferase (UGT) 1A1*28 polymorphism; irinotecan