title: New Perspectives in the Treatment of Advanced Gastric Cancer: S-1 as a Novel Oral 5-FU Therapy in Combination with Cisplatin.
abstract: Oral fluoropyrimidines have been available for more than 10 years. Capecitabine is well established in treating solid tumors in Europe. S-1 (Teysuno®), an oral formulation containing the 5-fluorouracil (5-FU) prodrug tegafur and the two enzyme modulators gimeracil and oteracil, has not been available in non-Asia countries until recently. In Japan, S-1 in combination with cisplatin is the recommended first-line treatment in patients with gastric cancer. In Europe, the first trials with S-1 were disappointing due to high unacceptable incidences of adverse events. Pharmacokinetic studies showed differences in Asian and Caucasian patients; therefore, a new non-Asian study program was initiated, which led to the pivotal phase 3 trial First-Line Advanced Gastric Cancer Study (FLAGS). In FLAGS, 1,053 patients with advanced gastric cancer from 24 non-Asian countries were enrolled. S-1 plus cisplatin showed no overall survival (OS) benefit when compared to 5-FU plus cisplatin. The primary endpoint superior OS was not met but better tolerability was shown. A post hoc noninferiority OS and safety analysis showed that S-1 plus cisplatin has the same efficacy as 5-FU plus cisplatin but a more favorable safety profile. This led to the approval of S-1 in combination with cisplatin in gastric cancer in Europe in 2011. This article reviews the mode of action of S-1, pivotal study results from an EU point of view, and future perspectives.
authors.affiliation: First Department of Medicine, Mutterhaus der Borromäerinnen, Trier, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Mahlberg
authors.forename: Sylvie
authors.initials: S
authors.lastname: Lorenzen
authors.forename: Peter
authors.initials: P
authors.lastname: Thuss-Patience
authors.forename: Volker
authors.initials: V
authors.lastname: Heinemann
authors.forename: Per
authors.initials: P
authors.lastname: Pfeiffer
authors.forename: Markus
authors.initials: M
authors.lastname: Möhler
mesh_terms: D000284:Administration, Oral; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use*; D006402:Hematologic Diseases / Q000209:etiology; D006801:Humans; D009367:Neoplasm Staging; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin; D005472:Fluorouracil