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

Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka, Japan.
Japanese Journal of Clinical Oncology (Impact Factor: 1.9). 10/2005; 35(9):520-5. DOI: 10.1093/jjco/hyi148
Source: PubMed

ABSTRACT 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.
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.
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.
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.

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