A Phase I Study of S-1 Administration and a 24-h Infusion of Cisplatin Plus Paclitaxel in Patients with Advanced Gastric Cancer

Abstract

Objective: The objective of this study was to determine the dose-limiting toxicity (DLT), the maximum tolerated dose (MTD), the recommended dose (RD) and the preliminary antitumor activity of S-1, oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimide, in combination with cisplatin and paclitaxel for advanced gastric cancer. Patients and Methods: Paclitaxel was administered on day 1. A fixed dose of S-1 (70 mg/m²/day) was orally administered for 14 consecutive days from day 1 and a 24-h infusion of a fixed dose of cisplatin (60 mg/m²) was administered on day 14 of every 28-day cycle. Four dose escalation levels of paclitaxcel were studied (120, 140, 160 and 180 mg/m²). Results: Twenty patients were enrolled. The toxicities were generally mild no grade 4 hematological toxicity or grade 3 non-hematological toxicity were observed. Level 4 was considered as the MTD because of a treatment delay of more than 2 weeks in 3 out of 6 patients. The RD of paclitaxcel was 160 mg/m². The overall response rate was 75%. Conclusion: A triple combination chemotherapy consisting of S-1, cisplatin and paclitaxel showed a tolerable level of adverse reactions and favorable antitumor activity.