S-1 in Gastric Cancer: a Comprehensive Review

Overview

Journal Gastric Cancer

Specialties Gastroenterology
Oncology

Date 2003 May 31

PMID 12775012

Citations 41

Authors

Yoshihiko Maehara

Affiliations

Soon will be listed here.

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.

Citing Articles

Long-Term Survival After Repeated Salvage Chemoradiation Therapy for Metastatic Lymph Node Recurrence in Advanced Gastric Cancer: A Case Report.

Katano A, Yamashita H Cureus. 2023; 15(3):e36649.

PMID: 37102033 PMC: 10123008. DOI: 10.7759/cureus.36649.

Analysis of treatment outcomes according to the cycles of adjuvant chemotherapy in gastric cancer: a retrospective nationwide cohort study.

Kim T, Ahn M, Choi Y, Kang S, Choi J, Lee H BMC Cancer. 2022; 22(1):948.

PMID: 36057562 PMC: 9440578. DOI: 10.1186/s12885-022-10006-7.

Efficacy and safety of low-dose apatinib plus S-1 versus regorafenib and fruquintinib for refractory metastatic colorectal cancer: a retrospective cohort study.

Dai Y, Sun L, Zhuang L, Zhang M, Zou Y, Yuan X J Gastrointest Oncol. 2022; 13(2):722-731.

PMID: 35557597 PMC: 9086039. DOI: 10.21037/jgo-22-285.

Comparison of Long-Term Efficacy in S-1 and Capecitabine With Oxaliplatin as Adjuvant Chemotherapy for Patients With Gastric Cancer After Curative Surgery: A Retrospective, Single-Center Observational Study.

Oh S, An J, Choi M, Lee J, Sohn T, Bae J Technol Cancer Res Treat. 2021; 20:15330338211039679.

PMID: 34605706 PMC: 8493307. DOI: 10.1177/15330338211039679.

Neoadjuvant and Adjuvant Chemotherapeutic Strategy of Colorectal Mixed Adeno-Neuroendocrine Carcinomas.

Michael A, Nath D Cureus. 2021; 13(7):e16645.

PMID: 34458045 PMC: 8384403. DOI: 10.7759/cureus.16645.

References

Ajani J, Ota D, Jackson D . Current strategies in the management of locoregional and metastatic gastric carcinoma. Cancer. 1991; 67(1 Suppl):260-5. DOI: 10.1002/1097-0142(19910101)67:1+<260::aid-cncr2820671309>3.0.co;2-2. View

Tatsumi K, Fukushima M, Shirasaka T, Fujii S . Inhibitory effects of pyrimidine, barbituric acid and pyridine derivatives on 5-fluorouracil degradation in rat liver extracts. Jpn J Cancer Res. 1987; 78(7):748-55. View

Piedbois P, Rougier P, Buyse M, Pignon J, Ryan L, Hansen R . Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer. J Clin Oncol. 1998; 16(1):301-8. DOI: 10.1200/JCO.1998.16.1.301. View

Kobayashi O, Konishi K, Kanari M, Cho H, Yoshikawa T, Tsuburaya A . Unusual survival for more than 2 years with peritoneal metastases of gastric cancer. Gastric Cancer. 2002; 5(1):47-50. DOI: 10.1007/s101200200007. View

Yoshikawa T, Kanari M, Tsuburaya A, Kobayashi O, Sairenji M, Motohashi H . Advanced gastric carcinoma successfully treated with TS-1 as neoadjuvant chemotherapy. Gastric Cancer. 2002; 3(3):171-175. DOI: 10.1007/pl00011714. View

Tsukioka Y, Matsumura Y, Hamaguchi T, Goto M, Muro K, Yamada Y . Complete response achieved following administration of S-1 in a patient with adrenal gland metastasis of 5-FU-resistant gastric cancer: a case report. Jpn J Clin Oncol. 2001; 31(9):450-3. DOI: 10.1093/jjco/hye091. View

Taguchi T, INUYAMA Y, Kanamaru R, Hasegawa K, Akazawa S, Niitani H . [Phase I study of S-1. S-1 Study Group]. Gan To Kagaku Ryoho. 1998; 24(15):2253-64. View

Schipper D, Wagener D . Chemotherapy of gastric cancer. Anticancer Drugs. 1996; 7(2):137-49. DOI: 10.1097/00001813-199602000-00001. View

Taguchi T, Sakata Y, Kanamaru R, Kurihara M, Suminaga M, Ota J . [Late phase II clinical study of RP56976 (docetaxel) in patients with advanced/recurrent gastric cancer: a Japanese Cooperative Study Group trial (group A)]. Gan To Kagaku Ryoho. 1998; 25(12):1915-24. View

10.

INUYAMA Y, Kida A, Tsukuda M, Kohno N, Satake B . [Early phase II study of S-1 in patients with advanced head and neck cancer. S-1 Cooperative Study Group (Head and Neck Working Group)]. Gan To Kagaku Ryoho. 1998; 25(8):1151-8. View

11.

Yamaguchi K, Tada M, Horikoshi N, Otani T, Takiuchi H, Saitoh S . Phase II study of paclitaxel with 3-h infusion in patients with advanced gastric cancer. Gastric Cancer. 2002; 5(2):90-5. DOI: 10.1007/s101200200015. View

12.

Furuse K, Kawahara M, Hasegawa K, Kudoh S, Takada M, Sugiura T . Early phase II study of S-1, a new oral fluoropyrimidine, for advanced non-small-cell lung cancer. Int J Clin Oncol. 2001; 6(5):236-41. DOI: 10.1007/pl00012111. View

13.

Iwazawa T, Kinuta M, Yano H, Matsui S, Tamagaki S, Yasue A . An oral anticancer drug, TS-1, enabled a patient with advanced gastric cancer with Virchow's metastasis to receive curative resection. Gastric Cancer. 2002; 5(2):96-101. DOI: 10.1007/s101200200016. View

14.

Moynihan T, Hansen R, Anderson T, Quebbeman E, Beatty P, AUSMAN R . Continuous 5-fluorouracil infusion in advanced gastric carcinoma. Am J Clin Oncol. 1988; 11(4):461-4. DOI: 10.1097/00000421-198808000-00010. View

15.

Taguchi T, Morimoto K, Horikoshi N, Takashima S, Toge T, Kimura M . [An early phase II clinical study of S-1 in patients with breast cancer. S-1 Cooperative Study Group (Breast Cancer Working Group)]. Gan To Kagaku Ryoho. 1998; 25(7):1035-43. View

16.

Takechi T, Fujioka A, Matsushima E, Fukushima M . Enhancement of the antitumour activity of 5-fluorouracil (5-FU) by inhibiting dihydropyrimidine dehydrogenase activity (DPD) using 5-chloro-2,4-dihydroxypyridine (CDHP) in human tumour cells. Eur J Cancer. 2002; 38(9):1271-7. DOI: 10.1016/s0959-8049(02)00048-5. View

17.

Ohtsu A, Baba H, Sakata Y, Mitachi Y, Horikoshi N, Sugimachi K . Phase II study of S-1, a novel oral fluorophyrimidine derivative, in patients with metastatic colorectal carcinoma. S-1 Cooperative Colorectal Carcinoma Study Group. Br J Cancer. 2000; 83(2):141-5. PMC: 2363492. DOI: 10.1054/bjoc.2000.1236. View

18.

Sobrero A, Kerr D, Glimelius B, Van Cutsem E, Milano G, Pritchard D . New directions in the treatment of colorectal cancer: a look to the future. Eur J Cancer. 2000; 36(5):559-66. DOI: 10.1016/s0959-8049(99)00314-7. View

19.

Ikeda M, Furukawa H, Imamura H, Shimizu J, Ishida H, Masutani S . Pharmacokinetic study of S-1, a novel oral fluorouracil antitumor agent in animal model and in patients with impaired renal function. Cancer Chemother Pharmacol. 2002; 50(1):25-32. DOI: 10.1007/s00280-002-0457-z. View

20.

Takiuchi H, Ajani J . Uracil-tegafur in gastric carcinoma: a comprehensive review. J Clin Oncol. 1998; 16(8):2877-85. DOI: 10.1200/JCO.1998.16.8.2877. View