title: A phase II Study of the global dose and schedule of capecitabine in Japanese patients with metastatic colorectal cancer.
abstract: BACKGROUND
  Although the standard 3-week capecitabine regimen (1250 mg/m(2) twice daily for 2 weeks followed by a 1-week rest) has shown superior activity and improved safety over bolus 5-fluorouracil/leucovorin in two large randomized phase III trials in Europe and in the United States, only a 4-week regimen of capecitabine (828 mg/m(2) twice daily for 3 weeks) has been studied in Japan. Therefore, we performed a phase II study to investigate the 3-week regimen of capecitabine in Japanese patients with metastatic colorectal cancer (MCRC).
  
  
  METHODS
  Previously untreated patients with MCRC received oral capecitabine 1250 mg/m(2) twice daily for 2 weeks. Treatment was repeated every 3 weeks. Blood and urine samples were collected for pharmacokinetic analysis.
  
  
  RESULTS
  Sixty patients were enrolled. The overall response rate was 35% [95% confidence interval (CI), 23-48%], and 52% of patients had stable disease. The median time to progression was 5.5 months (95% CI, 4.2-6.7 months). The median overall survival was 20.2 months (95% CI, 16.6-27.8 months). The most frequently occurring adverse drug reaction was hand-foot syndrome (all-grade 73%; grade 3 13%). Diarrhea, anorexia, nausea and stomatitis were each seen in 37% of patients. The pharmacokinetic profiles of capecitabine and its metabolites were similar to those reported in Caucasian patients.
  
  
  CONCLUSIONS
  The 3-week regimen of capecitabine was effective and well tolerated in Japanese patients with MCRC as well, and could be used as the basic regimen for future combination therapies.
authors.affiliation: Division of Gastroenterology, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan. ihyodo@md.tsukuba.ac.jp
authors.forename: Ichinosuke
authors.initials: I
authors.lastname: Hyodo
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Shirao
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Doi
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Hatake
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Arai
authors.forename: Kensei
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Takao
authors.initials: T
authors.lastname: Tamura
authors.forename: Shoji
authors.initials: S
authors.lastname: Takemiya
authors.forename: Hiroya
authors.initials: H
authors.lastname: Takiuchi
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Mishima
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000069287:Capecitabine; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D023381:Endpoint Determination; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D008175:Lung Neoplasms / Q000556:secondary; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil