title: A phase I study of infusional 5-fluorouracil, leucovorin, oxaliplatin and irinotecan in Japanese patients with advanced colorectal cancer who harbor UGT1A1*1/*1,*1/*6 or *1/*28.
abstract: OBJECTIVE
  To evaluate the safety and efficacy of combination chemotherapy with 5-fluorouracil (5-FU), leucovorin, irinotecan and oxaliplatin (FOLFOXIRI) in Japanese patients with advanced colorectal cancer.
  
  
  METHODS
  This phase I dose-finding study was designed to determine the maximum tolerated dose (MTD), recommended dose (RD) or both of FOLFOXIRI. Patients with UDP-glucuronosyltransferase (UGT) 1A1*6/*6, *28/*28 and *6/*28 genotypes were excluded, because these UGT1A1 genotypes are linked to severe neutropenia in Japanese.
  
  
  RESULTS
  A total of 10 Japanese patients with advanced colorectal cancer were studied. The MTD of FOLFOXIRI in these Japanese patients was 165 mg/m(2) irinotecan, 85 mg/m(2) oxaliplatin and 2,400 mg/m(2) 5-FU. Accordingly, the RD of FOLFOXIRI was determined to be 150 mg/m(2) irinotecan, 85 mg/m(2) oxaliplatin and 2,400 mg/m(2) 5-FU. Toxic effects, evaluated until the completion of 4 cycles, were manageable. Grade 3-4 neutropenia occurred in 27% of cycles, but there was no febrile neutropenia. Among the 9 assessable patients, the objective response rate was 89%.
  
  
  CONCLUSIONS
  We thus determined the RD of FOLFOXIRI in Japanese patients with advanced colorectal cancer who do not have UGT1A1*28/*28, *6/*6 or *6/*28 genotypes. Our results indicate that FOLFOXIRI is a well-tolerated regimen for these Japanese patients.
authors.affiliation: Department of Medical Oncology, International Medical Center-Comprehensive Cancer Center, Saitama Medical University, Hidaka, Japan. yu_s@saitama-med.ac.jp
authors.forename: Yu
authors.initials: Y
authors.lastname: Sunakawa
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Fujita
authors.forename: Wataru
authors.initials: W
authors.lastname: Ichikawa
authors.forename: Hiroo
authors.initials: H
authors.lastname: Ishida
authors.forename: Keishi
authors.initials: K
authors.lastname: Yamashita
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Araki
authors.forename: Keisuke
authors.initials: K
authors.lastname: Miwa
authors.forename: Kaori
authors.initials: K
authors.lastname: Kawara
authors.forename: Yuko
authors.initials: Y
authors.lastname: Akiyama
authors.forename: Wataru
authors.initials: W
authors.lastname: Yamamoto
authors.forename: Fumio
authors.initials: F
authors.lastname: Nagashima
authors.forename: Shigehira
authors.initials: S
authors.lastname: Saji
authors.forename: Yasutsuna
authors.initials: Y
authors.lastname: Sasaki
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D000077150:Oxaliplatin; D016896:Treatment Outcome; D000099148:UGT1A1 Enzyme
chemical_list: D002166:Camptothecin; D005472:Fluorouracil; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D002955:Leucovorin; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000099148:UGT1A1 Enzyme