Development History and Concept of an Oral Anticancer Agent S-1 (TS-1(R)): Its Clinical Usefulness and Future Vistas
Open Access
- 12 November 2008
- journal article
- review article
- Published by Oxford University Press (OUP) in Japanese Journal of Clinical Oncology
- Vol. 39 (1), 2-15
- https://doi.org/10.1093/jjco/hyn127
Abstract
Dushinsky et al. left a great gift to human beings with the discovery of 5-fluorouracil (5-FU). Approximately 50 years have elapsed from that discovery to the development of S-1 (TS-1®). The concept of developing an anticancer agent that simultaneously possesses both efficacy-enhancing and adverse reaction-reducing effects could be achieved only with a three-component combination drug. S-1 is an oral anticancer agent containing two biochemical modulators for 5-FU and tegafur (FT), a metabolically activated prodrug of 5-FU. The first modulator, 5-chloro-2,4-dihydroxypyridine (CDHP), enhances the pharmacological actions of 5-FU by potently inhibiting its degradation. The second modulator, potassium oxonate (Oxo), localizing in mucosal cells of the gastrointestinal (GI) tract after oral administration, reduces the incidence of GI toxicities by suppressing the activation of 5-FU in the GI tract. Thus, S-1 combines FT, CDHP and Oxo at a molar ratio of 1:0.4:1. In 1999–2007, S-1 was approved for the treatment of the following seven cancers: gastric, head and neck, colorectal, non-small cell lung, breast, pancreatic and biliary tract cancers. ‘S-1 and low-dose cisplatin therapy’ without provoking Grade 3 non-hematologic toxicities was proposed to enhance its clinical usefulness. Furthermore, ‘alternate-day S-1 regimen’ may improve the dosing schedule for 5-FU by utilizing its strongly time-dependent mode of action; the former is characterized by the low incidences of myelotoxicity and non-hematologic toxicities (e.g. ≤Grade 1 anorexia, fatigue, stomatitis, nausea, vomiting and taste alteration). These two approaches are considered to allow long-lasting therapy with S-1.Keywords
This publication has 64 references indexed in Scilit:
- S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trialThe Lancet Oncology, 2008
- Can Inhibiting Dihydropyrimidine Dehydrogenase Limit Hand-Foot Syndrome Caused by Fluoropyrimidines?Clinical Cancer Research, 2008
- Adjuvant Chemotherapy for Gastric Cancer with S-1, an Oral FluoropyrimidineThe New England Journal of Medicine, 2007
- Alternative pharmacokinetics of S-1 components, 5-fluorouracil, dihydrofluorouracil and ?-fluoro-?-alanine after oral administration of S-1 following total gastrectomyCancer Science, 2007
- CD16+CD57– Natural Killer Cells in Multifocal Motor NeuropathyEuropean Neurology, 2005
- S-1 Plus Cisplatin Combination Chemotherapy in Patients with Advanced Non–Small Cell Lung CancerClinical Cancer Research, 2004
- Alternate-day oral therapy with TS-1 for advanced gastric cancerInternational Journal of Clinical Oncology, 2004
- Comparative Pharmacokinetic Study of Continuous Venous Infusion Fluorouracil and Oral Fluorouracil With Eniluracil in Patients With Advanced Solid TumorsJournal of Clinical Oncology, 2002
- Late phase II study of novel oral fluoropyrimidine anticancer drug S-1 (1M tegafur–0.4M gimestat–1M otastat potassium) in advanced gastric cancer patientsEuropean Journal of Cancer, 1998
- Kinetics of proliferation of cancer cells in neoplastic effusions in manCancer, 1965