Phase I study of irinotecan and S-1 combination therapy in patients with metastatic gastric cancer

Int J Clin Oncol. 2003 Dec;8(6):374-80. doi: 10.1007/s10147-003-0359-z.


Background: Irinotecan plus intravenous 5-fluorouracil with leucovorin is effective against gastrointestinal cancer. S-1 is an oral fluoropyrimidine derivative combining tegafur with the modulators 5-chloro-2,4-dihydroxypyrimidine (a potent dihydropyrimidine dehydrogenase inhibitor), and potassium oxonate (an orotate phosphoribosyl transferase inhibitor), in a molar ratio of 1 : 0.4 : 1. S-1 has a high response rate, of about 40%, in advanced gastric cancer. A phase I study was conducted to assess the maximum tolerated dose and the recommended dose of the combination of irinotecan and S-1.

Methods: Irinotecan was given intravenously over the course of 90 min on day 1 and S-1 was given orally from days 1 to 14 of a 21-day cycle. The dose of S-1 was 80 mg/m2 per day, given in two divided doses. The dose of irinotecan was escalated in a stepwise fashion from 100 mg/m2 (level 1; n = 3), to 125 mg/m2 (level 2; n = 3), and 150 mg/m2 (level 3; n = 6).

Results: Dose-limiting toxicity did not occur during cycle 1, and the recommended dose for phase II studies was determined to be level 3, which was associated with grade 3 diarrhea in one patient, and with refusal to continue treatment because of prolonged fatigue in two patients. Grade 3 neutropenia developed in one of three patients at level 1 and level 2, and in two of six during cycle 1 of level 3. The recommended dose was determined to be 150 mg/m2 of irinotecan on day 1 and 80 mg/m2 per day of S-1 on days 1 to 14 of a 21-day cycle. Five of seven patients with measurable lesions had a partial response.

Conclusions: A combination of irinotecan and S-1 can be recommended for further phase II studies in patients with gastric cancer.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives*
  • Drug Combinations
  • Fatigue / etiology
  • Female
  • Humans
  • Infusions, Intravenous
  • Irinotecan
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neutropenia / chemically induced
  • Oxonic Acid / administration & dosage
  • Pyridines / administration & dosage
  • Stomach Neoplasms / drug therapy*
  • Tegafur / administration & dosage


  • Drug Combinations
  • Pyridines
  • S 1 (combination)
  • Tegafur
  • Oxonic Acid
  • Irinotecan
  • Camptothecin