title: Phase I/II study of irinotecan, UFT and leucovorin with hepatic arterial infusion using 5-FU in colorectal cancer patients with unresectable liver metastases.
abstract: OBJECTIVE
  To evaluate the efficacy and tolerability of systemic chemotherapy with irinotecan (CPT-11), UFT and leucovorin (LV) combined with hepatic arterial infusion (HAI) consisting of 5-fluorouracil (5-FU) in colorectal cancer patients with unresectable liver metastases.
  
  
  METHODS
  Patients were treated concurrently with escalating doses of intravenous CPT-11 (100, 120, and 140 mg/m²) on day 1 of each 14-day treatment cycle, with oral UFT (300 mg/m² per day) and LV (75 mg/body per day) on days 1-7 of each cycle, and with HAI 5-FU (2,000 mg/week) on days 8-14 of each cycle.
  
  
  RESULTS
  Twelve patients were enrolled in the phase I study. The maximum-tolerated dose was not reached. Consequently, the recommended dose of CPT-11 for the phase II study was determined to be 140 mg/m². Twenty-two patients were evaluated in the phase II study. Five patients experienced grade 3 neutropenia, two experienced grade 3 anorexia, two experienced nausea, and two experienced vomiting. An overall response was observed in 19 out of 22 patients (86.4%). The median progression-free survival period was 11.2 months, and the 3-year survival rate was 50.6%. Fourteen patients (63.6%) were ultimately able to undergo a complete liver resection.
  
  
  CONCLUSIONS
  Chemotherapy with CPT-11 and UFT/LV combined with HAI yielded a high response rate and enabled a significant proportion of patients with initially unresectable liver metastases to undergo surgical resection. Further trials are warranted.
authors.affiliation: Department of Surgery, Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital, Bunkyo-ku, Tokyo, 113-8867, Japan. tatsuro@yamaguchi.email.ne.jp
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Michiya
authors.initials: M
authors.lastname: Yasutome
authors.forename: Takeo
authors.initials: T
authors.lastname: Mori
authors.forename: Keiichi
authors.initials: K
authors.lastname: Takahashi
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007261:Infusions, Intra-Arterial; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary / Q000601:surgery; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D015996:Survival Rate; D005641:Tegafur / Q000008:administration & dosage; D016896:Treatment Outcome; D014498:Uracil / Q000008:administration & dosage
chemical_list: D005641:Tegafur; D014498:Uracil; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin