A Phase II Multicentric Trial of S-1 Combined with 24 h-infusion of Cisplatin in Patients with Advanced Gastric Cancer*

Background: The aim of this multicentric trial was to determine the clinical toxicities and antitumor effects of a chemotherapy regimen of S-1 combined with cisplatin in patients with inoperable locally or metastatic advanced gastric cancer. Patients and Methods: Forty-two patients were entered into the study. S-1 (80 mg/m 2 ) was administered orally daily for 14 consecutive days and 24-h infusion of cisplatin (70 mg/m 2 ) was administered on day 8 of every 28-day cycle. Results: The overall response rate was 50% and complete response rate was 5%. The most common adverse event was leucopenia, which occurred with grade 3 in 7 patients (16.6%) and grade 4 in 2 patients (4.8%). Non-hematological adverse events were generally mild. The median survival time was 342 days. The 2-year survival rate was 22.9%. Conclusion: This combination chemotherapy is active, convenient and well tolerated in patients with high-grade advanced gastric cancer. Synthesized by Duschinsky et al. in 1957, 5-fluorouracil |(5-FU) (1, 2) has been used widely for the treatment of various types of solid tumors. Since this drug has a short plasma half-life, many schedules for 5-FU administration have been investigated: continuous venous infusion (CVI) has shown the best antitumor effect (3). However, CVI of 5-FU restricts the quality of life of patients as it requires venous access and the use of a portable infusion pump. The dose administered is also limited by high incidences of mucositis, hand-foot syndrome and diarrhea (3, 4). Oral treatment is an attractive modality, since it is easy to administer and can be given in outpatient clinics. S-1 is a novel oral fluoropyrimidine anticancer agent designed to enhance anticancer activity and reduce gastrointestinal toxicity, by which a prodrug of 5-FU, tegafur (FT), has been combined with two modulating substances, gimestat (CDHP: a 5-chloro-2,4-dihydroxy-pyrimidine) and a potassium oxonate (Oxo) (5). The reported response rate for gastric cancer in S-1 was higher and the incidence of adverse reactions was lower compared to that for CVI of 5-FU (6- 8). Combined therapy with S-1 and other chemotherapeutic agents might yield an enhanced therapeutic benefit. We reported a dose-escalation study of S-1 combined with cisplatin for advanced gastric cancer and established a recommended protocol based on acceptable toxicity levels (9). In the present study, we conducted a phase II multicentric trial of S-1 in combination with cisplatin for high-grade advanced gastric cancer. The primary end-point was to determine the antitumor effect and clinical toxicities. The secondary end-point was overall survival.