Systemic chemotherapy plays a crucial role in treatment [3][4][5].Although combination chemotherapy has been studied extensively, there is no internationally accepted standard of care for patients with advanced gastric cancer [4][5][6][7]. Worldwide, the combination of 5-fl uorouracil (5-FU) and cisplatin is a mainstay in the treatment of advanced gastric cancer. Recently, oral fl uoropyrimidines have been emerging as a breakthrough treatment [6]. The use of oral agents has potential advantages, from patient convenience to avoiding the need for indwelling venous access and infusion pumps [7,8]. An oral fl uoropyrimidine, S-1, is a fourthgeneration fl uoropyrimidine containing tegafur, 5-chloro-2, 4-dihydroxypyridine, and potassium oxonate [9]. Interesting results have been accumulating in evaluating S-1 combination therapies, particularly with platinum drugs. In this study, we reviewed phase I/II studies of combination chemotherapy with S-1 and platinum in patients with metastatic or recurrent gastric cancer.
S1 + cisplatin trials in AsiaThe combination of S-1 and cisplatin is logical, given the biochemical modulation it offers: the inhibition of methionine uptake into tumor cells by cisplatin results in the enhancement of 5-FU cytotoxicity [10]. Since the fi rst phase I trial of S-1 in 1997 [11], many phase I/II studies have been conducted in Japan and have yielded promising results.One of the notable results of the phase II studies of S-1 and cisplatin was reported by Koizumi et al. [12]. S-1 was administered daily at a dose of 80 mg/m 2 per day for 3 weeks, followed by a 2-week rest, with cisplatin at 60 mg/m 2 given on day 8. This regimen had a 5-week cycle, and the response rate was 74%. Using the same regimen, the authors of two other studies also reported high response rates, of 67% and 66.7%, respecAbstract Despite the progress in treatment protocols, gastric cancer remains a challenging disease. Systemic chemotherapy is of crucial importance for patients with metastatic or recurrent disease, and new developments in chemotherapy regimens have been seen in recent years. An oral 5-fl uororacil (5-FU) agent, S-1, is emerging, with promising results. Various S-1 combination regimens, mostly with cisplatin, are being examined extensively, and the combination of S-1 with oxaliplatin is the focus of recent studies. In this study, phase I/II studies of combination chemotherapy with S-1 and platinum in patients with metastatic or recurrent gastric cancer were reviewed. We found that the combination of S-1 plus cisplatin was highly active against advanced gastric cancer, with a favorable toxicity profi le. The response rates were 53%-74% in Japan, 47.6% in Korea, and 51% in the United States and Europe. There is no internationally accepted standard care for patients with advanced gastric cancer yet, but S-1 is likely to replace infusional 5-FU, and oxaliplatin may represent an alternative to cisplatin in the near future. More innovative therapies, particularly with molecular-targeted drugs, are needed to meet the ...