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S-1 in gastric cancer: a comprehensive review
1Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Abstract:
The current basic and clinical studies of S-1 (TS-1) were reviewed. S-1 is a novel oral dihydropyrimidine dehydrogenase (DPD) inhibitory fluoropyrimidine (DIF) based on a biochemical modulation of 5-fluorouracil (5-FU); S-1 contains tegafur (FF) and two types of enzyme inhibitor, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (Oxo) in a molar ratio of 1:0.4:1. In pharmacokinetic studies, S-1 showed high 5-FU concentration in blood for long periods of time. In a combined analysis of two pivotal late phase II studies in gastric cancer, the overall response rate was 44.6% (45/101), and median survival time and 1-year survival rate were 244 days and 37%, respectively. A postmarketing survey was conducted, and in the interim analysis, tolerability and safety profiles were shown in 3294 patients with gastric cancer. The oral dose form and low incidence of adverse reactions permit treatment on an outpatient basis. To evaluate the survival benefit of S-1 in advanced gastric cancer, a phase III study of S-1 vs 5-FU vs cisplatin (CDDP) plus irinotecan (CPT-11) has been conducted. The effect of S-1 in adjuvant chemotherapy is also promising. Currently, a phase III study of surgery alone vs S-1 in patients with curative resection of gastric cancer is in progress. Further therapeutic benefits are expected to be gained by combining S-1 with other chemotherapeutic agents. Several preliminary results of combination phase I/II studies of S-1 with CDDP or CPT-11 have recently been obtained, and phase II studies are in progress. Thus, S-1 is currently the first candidate as the standard anticancer drug for gastric cancer. Further evaluations by well-controlled clinical trials are still needed.
Insights
S-1, an oral fluoropyrimidine, demonstrates efficacy in gastric cancer treatment with a 44.6% response rate. This novel drug offers a favorable safety profile for outpatient use and is a leading candidate for standard gastric cancer therapy.
Area of Science:
- Oncology
- Pharmacology
- Gastroenterology
Background:
- S-1 is an oral dihydropyrimidine dehydrogenase (DPD) inhibitory fluoropyrimidine (DIF) drug.
- It comprises tegafur (FF), 5-chloro-2,4-dihydroxypyridine (CDHP), and potassium oxonate (Oxo).
Purpose of the Study:
- To review current basic and clinical studies of S-1 for gastric cancer.
- To evaluate S-1's efficacy, safety, and potential as a standard treatment for gastric cancer.
Main Methods:
- Review of existing basic and clinical studies, including phase II and III trials.
- Analysis of pharmacokinetic data, postmarketing surveillance, and ongoing clinical trials.
Main Results:
- Phase II studies showed a 44.6% overall response rate in gastric cancer patients.
- S-1 demonstrated prolonged high 5-FU blood concentrations and a favorable safety profile for outpatient administration.
- Ongoing phase III trials are evaluating S-1 against other standard treatments and in adjuvant settings.
Conclusions:
- S-1 is a promising oral anticancer drug for gastric cancer, with potential as a new standard therapy.
- Further clinical trials are necessary to confirm its long-term benefits and optimal use in combination therapies.