Phase I Study of S-1 Combined with Irinotecan (CPT-11) in Patients with Advanced Gastric Cancer (OGSG 0002)

• Published in: Japanese journal of clinical oncology Vol. 35; no. 9; pp. 520 - 525
• Main Authors: Takiuchi, Hiroya, Narahara, Hiroyuki, Tsujinaka, Toshimasa, Gotoh, Masahiro, Kawabe, Sei-ichiro, Katsu, Ken-ichi, Iishi, Hiroyasu, Tatsuta, Masaharu, Fujitani, Kazumasa, Furukawa, Hiroshi, Taguchi, Tetsuo
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.09.2005; Oxford Publishing Limited (England)
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Camptothecin - administration & dosage; Camptothecin - adverse effects; Camptothecin - analogs & derivatives; combination chemotherapy; Drug Combinations; Female; Humans; irinotecan; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Staging; Oxonic Acid - administration & dosage; Oxonic Acid - adverse effects; pharmacokinetics; Pyridines - administration & dosage; Pyridines - adverse effects; S-1; Stomach Neoplasms - drug therapy; Stomach Neoplasms - pathology; Survival Rate; Tegafur - administration & dosage; Tegafur - adverse effects; Treatment Outcome
• ISSN: 0368-2811; 1465-3621
• DOI: 10.1093/jjco/hyi148

Objective: A dose-escalation study of irinotecan (CPT-11) combined with S-1, a novel oral fluoropyrimidine, was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD) and dose-limiting toxicities (DLTs) in advanced gastric cancer. Methods: S-1 was administered orally at 80 mg/m2/day for 21 consecutive days followed by a 2 week rest. CPT-11 was given intravenously on days 1 and 15 of each course, at an initial dose of 40 mg/m2/day, stepping up to 60, 80, 100 or 120 mg/m2/day depending on the DLT. Courses were repeated every 5 weeks, unless disease progression or severe toxicity was observed. At a level of the RD, five patients were added to conduct a pharmacokinetic (PK) study. Results: A total of 24 patients were entered in this study. The MTD of CPT-11 was considered to be 100 mg/m2, because 50% of the patients (3/6) developed DLTs, diarrhea and rash. Therefore, the RD of CPT-11 was set at the dose immediately below 80 mg/m2. The overall response rate (RR) by the criteria of the Japanese Research Society of Gastric Cancer was 58.3% (14/24) and the RR at the RD was 66.7% (6/9), suggesting promising clinical efficacy. There were no significant differences between the PK parameters of S-1 on days 10 and 15. Conclusions: S-1 with CPT-11 can be combined safely without CPT-11 effect on S-1 PK data and holds promise as an effective regimen for advanced gastric cancer.