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Phase I and Pharmacokinetic Study of S-1 Combined with Weekly Paclitaxel in Patients with Advanced Gastric Cancer

2005; Karger Publishers; Volume: 69; Issue: 5 Linguagem: Inglês

10.1159/000089996

1423-0232

Kazumasa Fujitani, Hiroyuki Narahara, Hiroya Takiuchi, Toshimasa Tsujinaka, Eriko Satomi, Masahiro Gotoh, Motohiro Hirao, Hiroshi Furukawa, T Taguchi,

Colorectal Cancer Treatments and Studies

<i>Objective:</i> A dose-escalation study of weekly paclitaxel combined with S-1, a novel oral fluoropyrimidine, was performed to determine the maximum tolerated dose (MTD), the recommended dose (RD) and the dose-limiting toxicities (DLTs) in advanced gastric cancer. <i>Patients and Methods:</i> Twelve patients were enrolled. S-1 was given orally at a fixed dosage of 40 mg/m² b.i.d. for 14 consecutive days, followed by a 1-week rest. Paclitaxel was scheduled to be given intravenously on days 1 and 8 at a dose of 50, 60, 70 or 80 mg/m², depending on the DLTs. Treatment was repeated every 3 weeks. A pharmacokinetic study was conducted in an additional 5 patients on days 7 and 8 during the first course given at the RD. <i>Results:</i> The MTD of paclitaxel was presumed to be 60 mg/m², because 50.0% of patients (2/4) developed DLTs (mainly grade 3 anorexia). DLT was observed in 1 out of 8 patients at a dose of 50 mg/m². Therefore, the RD of paclitaxel was estimated to be 50 mg/m². The preliminary response rate was 62.5% (5/8) at the RD. There were no significant pharmacokinetic interactions between S-1 and paclitaxel. An adequate plasma paclitaxel concentration for an antineoplastic effect was achieved with weekly doses of 50 mg/m². <i>Conclusion:</i> Weekly paclitaxel combined with S-1 was demonstrated to exhibit a tolerable toxicity profile with therapeutic plasma concentration at the dose of 50 mg/m². This regimen could represent a novel and low toxic combination for advanced gastric cancer.