The need for a new fluoropyrimidine in advanced gastric cancer treatment

Eric Van Cutsem, Daniel G. Haller, Albert Sobrero, Yasuhide Yamada, Jean Yves Douillard, Markus Moehler

Research output: Contribution to journalArticlepeer-review


Fluoropyrimidines have shown efficacy against a variety of cancers and have evolved into a range of different uses and formulations. These drugs have been tested extensively as monotherapies and as part of numerous different chemotherapy combinations. The efficacy and safety profile of bolus intravenous (IV) 5-fluorouracil (5-FU) has been improved by continuous IV administration. The availability of the first 5-FU oral form in Europe, capecitabine, has added a clear value in terms of convenience for patients, while forcing physicians and nurses to learn how to manage the toxicity profile of this compound. S-1 is a new oral formulation combining a 5-FU prodrug (tegafur) and two targeted modulators of its metabolism (gimeracil and oteracil) preserving the efficacy and improving the safety of the prodrug. S-1 has become the backbone treatment for advanced gastric cancer in Japan since its introduction in 1999. Extensive experience from clinical trials, post-marketing studies and patient registries of over 4,000 patients in Japan show that S-1 has improved measures of survival in advanced gastric cancer and has an acceptable safety profile. S-1 has recently been approved for advanced gastric cancer treatment in Europe. Since 5-FU metabolism differs between Asian and Caucasian populations, the introduction of S-1 in Caucasians has necessitated an entirely new clinical trial programme. Phase I trials indicated different dose levels were necessary in Westerners versus Asians (25 versus 40 mg/m2). In the FLAGS study of over 1,000 patients with advanced gastric cancer (the largest study ever conducted in this indication), S-1 plus cisplatin was demonstrated to be non-inferior in efficacy but superior in safety to 5-FU + cisplatin. Based on these results, S-1 was approved in Europe in March 2011 under the trade name Teysuno®. Further clinical trials are in progress to evaluate S-1 in advanced gastric cancer (AGC) and its use as part of triplet therapies is currently being investigated. This will further define the role of S-1 as a key part of advanced gastric cancer management in Western countries.

Original languageEnglish
Pages (from-to)232-240
Number of pages9
JournalEuropean Oncology and Haematology
Issue number4
Publication statusPublished - Nov 2012


  • 5-fluorouracil (5-FU)
  • Advanced gastric cancer
  • Caucasian
  • Fluoropyrimidines
  • S-1 (tegafur/gimeracil/oteracil)

ASJC Scopus subject areas

  • Hematology
  • Oncology


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