Phase I study of S-1 combined with irinotecan (CPT-11) in patients with advanced gastric cancer (OGSG 0002).

Abstract

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/m(2)/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/m(2)/day, stepping up to 60, 80, 100 or 120 mg/m(2)/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/m(2), 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/m(2). 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.

• Authors: Hiroya Takiuchi, Hiroyuki Narahara, Toshimasa Tsujinaka, Masahiro Gotoh, Sei-ichiro Kawabe, Ken-ichi Katsu, Hiroyasu Iishi, Masaharu Tatsuta, Kazumasa Fujitani, Hiroshi Furukawa, Tetsuo Taguchi, Osaka Gastrointestinal Cancer Chemotherapy Study Group (OGSG)
• Journal: Japanese journal of clinical oncology (Jpn J Clin Oncol) Vol. 35 Issue 9 Pg. 520-5 (Sep 2005) ISSN: 0368-2811 [Print] England
• PMID: 16141295 (Publication Type: Clinical Trial, Phase I, Journal Article)

Chemical References

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

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, pharmacokinetics, therapeutic use)
• Camptothecin (administration & dosage, adverse effects, analogs & derivatives)
• Drug Combinations
• Female
• Humans
• Irinotecan
• Male
• Maximum Tolerated Dose
• Middle Aged
• Neoplasm Staging
• Oxonic Acid (administration & dosage, adverse effects)
• Pyridines (administration & dosage, adverse effects)
• Stomach Neoplasms (drug therapy, pathology)
• Survival Rate
• Tegafur (administration & dosage, adverse effects)
• Treatment Outcome