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S-1 is a combination of three pharmacological compounds, namely tegafur, gimeracil, and oteracil potassium. Tegafur is a prodrug of 5-fluorouracil (5-FU), an oral fluoropyrimidine, and it has been developed as a replacement for infusional 5-FU therapy. S-1-based chemotherapy and the combination of S-1 and cisplatin are the most reasonable first-line standards for unresectable advanced gastric cancer in Japan. However, the application of S-1 for gastric cancer has been delayed in Western countries. One reason for this delay is that the pharmacokinetics of tegafur is affected by polymorphisms in cytochrome P-450 2A6, and consequently 5-FU concentrations in the plasma are more likely to be elevated in patients from Western countries. Although the dose of S-1 was reduced compared with the approved dose in Japan, a global Phase III study reported similar results regarding overall survival between S-1 plus cisplatin and infusional 5-FU plus cisplatin arms. Significant safety advantages were observed in the S-1 plus cisplatin arm compared with the infusional 5-FU plus cisplatin arm. S-1 plus cisplatin has become acceptable for Western countries, also, as a choice for unresectable advanced gastric cancer. Comparisons with capecitabine and combination of several targeting agents with S-1 are expected in the future.

oncotargets and therapy

Tegafur/gimeracil/oteracil (S-1) approved for the treatment of advanced gastric cancer in adults when given in combination with cisplatin: a review comparing it with other fluoropyrimidine-based therapies