title: Phase 1/2 clinical study of irinotecan and oral S-1 (IRIS) in patients with advanced gastric cancer.
abstract: BACKGROUND
  Irinotecan and S-1, an oral fluoropyrimidine composed of tegafur, gimeracil, and oteracil potassium, have demonstrated antitumor activity against advanced gastric cancer. We performed a phase 1/2 study to determine the recommended dose, antitumor activity, and safety of a combination of S-1 and irinotecan in patients with advanced gastric cancer.
  
  
  METHODS
  Patients with previously untreated advanced gastric cancer were enrolled. Patients received irinotecan intravenously on days 1 and 15 plus oral S-1 twice daily on days 1-14 of a 28-day cycle. In the phase 1 part, the dose of irinotecan was escalated from 100 mg/m(2) to 125 mg/m(2) and then to 150 mg/m(2).
  
  
  RESULTS
  A total of 24 patients were enrolled. Overall, the median number of treatment cycles per patient was 5.9, and 92% of the patients completed at least two cycles. The overall response rate was 54.2% (13 of 24). The response rates in differentiated and undifferentiated cancer were 56.3% (nine of 16) and 50.0% (four of eight), respectively. Median survival time was 581 days. The maximum tolerated dose of irinotecan was not reached at the highest level. However, grade 4 neutropenia occurred at 125 mg/m(2). We concluded that the recommended dose of irinotecan for the present regimen was 125 mg/m(2).
  
  
  CONCLUSIONS
  Treatment with S-1+irinotecan is considered effective in patients with advanced gastric cancer who have not previously received chemotherapy. A combination of irinotecan and S-1 was well tolerated in patients with advanced gastric cancer and could be given on an outpatient basis.
authors.affiliation: Department of Gastroenterology, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido 060-8638, Japan. ykomatsu@med.hokudai.ac.jp
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Komatsu
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yuki
authors.forename: Nozomu
authors.initials: N
authors.lastname: Fuse
authors.forename: Takashi
authors.initials: T
authors.lastname: Kato
authors.forename: Takuto
authors.initials: T
authors.lastname: Miyagishima
authors.forename: Mineo
authors.initials: M
authors.lastname: Kudo
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kunieda
authors.forename: Miki
authors.initials: M
authors.lastname: Tateyama
authors.forename: Osamu
authors.initials: O
authors.lastname: Wakahama
authors.forename: Takashi
authors.initials: T
authors.lastname: Meguro
authors.forename: Yuh
authors.initials: Y
authors.lastname: Sakata
authors.forename: Masahiro
authors.initials: M
authors.lastname: Asaka
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004338:Drug Combinations; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D055815:Young Adult
chemical_list: D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000077146:Irinotecan; D002166:Camptothecin