S-1 (Teysuno®): A Review of Its Use in Advanced Gastric Cancer in Non-Asian Populations

Abstract

S-1 (Teysuno(®)) is an oral anticancer agent comprising the 5-fluorouracil (5-FU) prodrug tegafur and targeted modulators, gimeracil and oteracil. S-1 in combination with cisplatin is a recommended first-line treatment for gastrointestinal cancers in Japan and has recently been approved in the EU for the treatment of advanced gastric cancer. This article reviews S-1 pharmacology from an EU perspective. In a randomized, open-label trial in 24 non-Asian countries in patients with advanced gastric cancer, there were no significant differences between S-1 plus cisplatin and 5-FU plus cisplatin groups in median overall survival (OS) [primary endpoint], progression-free survival or overall response rate. In a post hoc analysis of OS, S-1 plus cisplatin was noninferior to 5-FU plus cisplatin. There were no significant between-group differences in patient quality of life, according to the Functional Assessment of Cancer Therapy (Gastric) Trial Outcome Index, except that S-1 plus cisplatin recipients had a significantly longer time to worsening in physical well-being than 5-FU plus cisplatin recipients. Overall, S-1 plus cisplatin was better tolerated than 5-FU plus cisplatin, with significantly lower rates of haematological, some gastrointestinal tract and other adverse events, serious adverse events and deaths resulting from toxicity, along with significantly fewer haematological and renal function abnormalities. Compared with 5-FU, S-1 plus cisplatin recipients had significantly higher rates of hand-foot syndrome and hyperbilirubinaemia, although there were no between-group differences in the proportions of patients with increased liver enzymes. S-1 is a useful alternative to 5-FU for patients with advanced gastric cancer.

Experience with S-1 in older Caucasian patients with metastatic colorectal cancer (mCRC): Findings from an observational chart review

“…While there is generally a consensus on the most appropriate dose of oxaliplatin to use (i.e. 130 mg/m 2 ) when administered every three weeks with S-1 or capecitabine [9,10,23,24] The optimal dosing for patients aged > 80, balancing response and side effects is not known. However, our preliminary results in this population shows that a monotherapy schedule with 25 mg/m 2 is tolerable with promising activity.…”

“…The optimal schedule of S-1 and irinotecan or oxaliplatin has not been well established in Caucasian patients with mCRC [10], but based on data from Asian patients and knowledge from the use of other oral fluoropyrimidines in Caucasian patients with mCRC we used the following doses:…”

“…The third-generation oral fluoropyrimidine S-1 (Teysuno V R ) is associated with a lower rate of adverse events than capecitabine, particularly hand-foot syndrome (HFS) [8][9][10]. S-1 is currently approved for several indications including gastric, colorectal, non-small cell lung, breast, pancreatic, biliary tract and head and neck cancer in Japan but only for gastric cancer in the European Union.…”

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

“…However, in the last two decades, many efforts have been made to improve efficacy and reduce toxicity of 5-FU-based cancer therapy. The development of 5-FU prodrugs, like tegafur and capecitabine, allowed oral administration and prolonged action of 5-FU at lower peak concentrations, thereby improving tolerability [5]. Oral administration reduces the morbidity encountered with intravenous infusion, and thus enhances convenience and also quality of life.…”

“…S-1 has been used for more than 10 years in the treatment of advanced gastric cancer in many Asian countries, including Japan and Korea. Efficacy and safety of S-1 has been proven in several Japanese phase II and phase III studies [5]. Noninferiority of S-1 monotherapy versus 5-FU infusion was shown in the Japanese phase III study JCOG9912 [8].…”