Phase I study of gemcitabine, cisplatin, and S-1 combination therapy for patients with untreated advanced biliary tract cancer.

ABSTRACT

BACKGROUND: To develop a triplet regimen containing gemcitabine, cisplatin, and S-1 (GPS), we assessed the recommended dose for patients with untreated advanced biliary tract cancer in this phase I study. METHODS: Dose-limiting toxicities (DLTs) were evaluated for the following two dose levels gemcitabine (1000 mg/m(2) for level 1 and 1200 mg/m(2) for level 2 on day 1), cisplatin (30 mg/m(2) fixed dose on day 1), and S-1 (40-60 mg/day fixed dose twice a day for 7 days), every 2 weeks until progression. DLTs for each level were evaluated in six or more patients during the first two cycles. RESULTS: A total of 18 patients were enrolled and 16 patients were evaluated. DLTs at level 1 were observed in two of 10 patients. At level 2, a DLT was observed in one of six patients. The main grade 3 or 4 treatment-related adverse events were neutropenia and leukopenia, and a few non-hematological toxicities were observed. Among 14 patients with measurable lesions, the best response rate was 50%. CONCLUSIONS: GPS with a relative dose intensity corresponding to 90% of the standard gemcitabine plus cisplatin regimen could be administered safely, and showed preliminary antitumor activity. Survival benefits will be studied subsequently.