title: Phase I/II study of sequential therapy with irinotecan and S-1 for metastatic colorectal cancer.
abstract: BACKGROUND
  Both irinotecan (CPT-11) and S-1 are active against colorectal cancer; however, as S-1 is a prodrug of 5-fluorouracil (5-FU), 5-FU and its metabolites might inhibit the antitumour effect of CPT-11. Therefore, we designed a sequential combination, in which CPT-11 infusion was given on day 1 and S-1 was given orally at 80 mg m(-2) per day on days 3-16 every 3 weeks.
  
  
  METHODS
  Twelve patients entered the phase I study, and the recommended doses were determined as a CPT-11 dose of 150 mg m(-2) and an S-1 dose of 80 mg m(-2).
  
  
  RESULTS
  In all, 36 patients entered the phase II study, of whom 4 and 16 had complete and partial responses. The overall response rate was 55.6% (95% confidence interval, 38.1-72.1%), and median progression-free survival was 7.7 months (95% confidence interval, 4.8-12.6 months). Grade 3 neutropenia was the most common haematological toxicity and occurred in 6.5% of 215 treatment courses. Grade 3 non-haematological toxicities included anorexia (1.4%) and diarrhoea (0.9%). There was no grade 4 toxicity of any kind.
  
  
  CONCLUSIONS
  Our results suggest that this regimen is convenient, safe and promising, compared with conventional regimens for patients with metastatic colorectal cancer.
authors.affiliation: Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba ward, Sendai 980-8575, Japan. ytakashi@med.id.yamagata-u.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Yoshioka
authors.forename: S
authors.initials: S
authors.lastname: Kato
authors.forename: M
authors.initials: M
authors.lastname: Gamoh
authors.forename: N
authors.initials: N
authors.lastname: Chiba
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: N
authors.initials: N
authors.lastname: Sakayori
authors.forename: S
authors.initials: S
authors.lastname: Kato
authors.forename: H
authors.initials: H
authors.lastname: Shibata
authors.forename: H
authors.initials: H
authors.lastname: Shimodaira
authors.forename: K
authors.initials: K
authors.lastname: Otsuka
authors.forename: Y
authors.initials: Y
authors.lastname: Kakudo
authors.forename: S
authors.initials: S
authors.lastname: Takahashi
authors.forename: C
authors.initials: C
authors.lastname: Ishioka
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004338:Drug Combinations; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000077146:Irinotecan; D002166:Camptothecin