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. 2008 Dec 3;39(1):2–15. doi: 10.1093/jjco/hyn127

Table 1.

Timeline: from the discovery of 5-FU to the development of S-1 (TS-1®)

Years Events
1957 (i) Synthesis of 5-FU and discovery of its antitumor activity by Dushinsky et al. (3).
1967 (ii) Synthesis of FT by Hiller et al. (11) at the Latvian Institute of Synthesis, USSR
June 1969 Encounter with FT (Futraful®): Y. Kobayashi, the President of Taiho met with Blokhin the President Cancer Research Center, USSR Academy of Medical Science
December 1969 Introduction of FT by Taiho Pharmaceutical Co., Ltd
1970 Development of FT from the intravenous to oral agent by Kimura, Fujii and Taguchi
1976 (iii) Invention by Fujii et al. (16) of UFT® (oral combination drug), FT:Ura =1:4
1984 Discovery of an inhibitor for 5-FU catabolic enzyme, CDHP by Tatsumi et al. (17)
May 1987 Discovery of Oxo that reduces 5-FU-induced gastrointestinal toxicities by Shirasaka et al. (18)
November 1990 Establishment of the S-1 project by Y. Kobayashi
January 1991 (iv) Invention of S-1 by Shirasaka et al. (19) S-1, FT:CDHP:Oxo =1:0.4:1
March 1991 Onset of preclinical studies
November 1992 Onset of Phase I clinical trials
March 1994 Onset of Phase II clinical trials
November 1997 NDA of S-1 for gastric cancer
January 1999 Approval of S-1 (TS-1®) for gastric cancer through the priority review system (20,21)
April 2001 Approval of S-1 for head and neck cancer (22)
December 2003 Approval of S-1 for colorectal cancer (23,24)
December 2004 Approval of S-1 for non-small cell lung cancer (25)
November 2005 Approval of S-1 for breast cancer (26)
August 2006 Approval of S-1 for pancreatic cancer (27)
August 2007 Approval of S-1 for biliary tract cancer (28)
2008 Phase III studies of S-1 (29,30)

FT, tegafur; CDHP, 5-chloro-2,4-dihydroxypyridine; Oxo, potassium oxonate; NDA, new drug application.