title: Phase I/II study of irinotecan and UFT for advanced or metastatic colorectal cancer.
abstract: The aim of this study was to determine the recommended dose of irinotecan in combination with the fixed dose of oral UFT as first-line therapy in patients with advanced or recurrent colorectal cancer, and to evaluate the response rate and overall survival as a phase II study.
  
  
  METHODS
  Thirteen patients were recruited into a phase I trial. Four doses of irinotecan ranging from 60 to 150 mg/m2/day were administered intravenously on day 1 and day 16 in combination with UFT given orally from day 2 to day 15. In a phase II study, 53 patients received at least one cycle of this therapy.
  
  
  RESULTS
  The recommended dose of this combination was determined as irinotecan 120 mg/m2/day and UFT 400 mg/m2/day. Dose-limiting toxicities were neutropenia and prolonged leucopenia. On an intent-to-treat analysis, the response rate in the phase II study was 24.5% (95% confidence interval 13.8% to 38.2%). The median overall survival time was 20.3 months (95% confidence interval, 15.0-22.8 months). Out of 20 patients with stable disease, 17 who received more than 4 cycles of the regimen lived longer than the other 3 patients who received fewer than 3 cycles (p = 0.0353). Hematological adverse events were mainly grade 3/4 neutropenia observed in 6 out of 53 patients. Grade 3 non-hematological toxicities, such as diarrhea, anorexia, nausea/vomiting and alopecia were observed in 6 patients.
  
  
  CONCLUSIONS
  Irinotecan combined with oral UFT was effective and well-tolerated. This regimen may be considered as a first-line therapy for advanced or metastatic colorectal cancer and may result in fairly long survival, even for patients with stable disease.
authors: Department of Surgery and Oncology, and 2First Department of Internal Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. mibu@shs.kyushu-u.ac.jp
authors: R
authors: R
authors: Mibu
authors: S
authors: S
authors: Tanaka
authors: K
authors: K
authors: Futami
authors: K
authors: K
authors: Shimada
authors: M
authors: M
authors: Hotokezaka
authors: S
authors: S
authors: Nakahara
authors: H
authors: H
authors: Ichimiya
authors: H
authors: H
authors: Kido
authors: Y
authors: Y
authors: Hirano
authors: T
authors: T
authors: Kashiwagi
authors: T
authors: T
authors: Eguchi
authors: K
authors: K
authors: Mitsuki
authors: K
authors: K
authors: Mizumoto
authors: M
authors: M
authors: Tanaka
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 / Q000009:adverse effects / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D014498:Uracil / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D005641:Tegafur; D014498:Uracil; D000077146:Irinotecan; D002166:Camptothecin