New Perspectives in the Treatment of Advanced Gastric Cancer: S-1 as a Novel Oral 5-FU Therapy in Combination with Cisplatin

Mahlberg, Rolf; Lorenzen, Sylvie; Thuss-Patience, Peter; Heinemann, Volker; Pfeiffer, Per and Mohler, Markus (2017): New Perspectives in the Treatment of Advanced Gastric Cancer: S-1 as a Novel Oral 5-FU Therapy in Combination with Cisplatin. In: Chemotherapy, Vol. 62, No. 1: pp. 62-70

Abstract

Oral fluoropyrimidines have been available for more than 10 years. Capecitabine is well established in treating solid tumors in Europe. S-1 (Teysuno (R)), 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. (C) 2016 S. Karger AG, Basel

• Item Type: Journal article
• Faculties: Medicine
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 0009-3157
• Language: English