CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2015; 36(04): 219-228
DOI: 10.4103/0971-5851.171542
REVIEW ARTICLE

Emerging role of S-1 in gastric cancer

Eriseld Krasniqi
Department of Systems Medicine, Medical Oncology, University of Rome ′Tor Vergata′, Tor Vergata Clinical Center, Rome, Italy
,
Stefania Pellicori
Department of Systems Medicine, Medical Oncology, University of Rome ′Tor Vergata′, Tor Vergata Clinical Center, Rome, Italy
,
Vincenzo Formica
Department of Systems Medicine, Medical Oncology, University of Rome ′Tor Vergata′, Tor Vergata Clinical Center, Rome, Italy
› Author Affiliations
Financial support and sponsorship Nil.

Abstract

Gastric cancer remains one of the most important malignancies worldwide in terms of incidence and mortality. The treatment is based on the combination of local surgery and radiation therapy as well as systemic chemotherapy and targeted molecules. Fluoropyrimidines and particularly 5-fluorouracil (FU) represent still the backbone for gastric cancer chemotherapy and new molecular versions of this molecule have been brought to clinical practice in order to improve benefits and reduce adverse effects. S-1 is an oral prodrug of 5-FU, which has demonstrated high effectiveness for gastric cancer treatment and a favorable safety profile. Currently, there are geographic differences in the treatment of gastric cancer and in the use of S-1, which is a mainstay of gastric cancer management in Eastern countries, but is not part of the standard care in the rest of the world. In this review, we gathered data from phase I, II, and III trials of S-1 in gastric cancer, in order to define its real benefit-risk ratio and assess whether geographic differences in S-1 use are justified by unchangeable factors.



Publication History

Publication Date:
12 July 2021 (online)

© 2015. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

 
  • References

  • 1 Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61:69-90.
  • 2 Forman D, Burley VJ. Gastric cancer: Global pattern of the disease and an overview of environmental risk factors. Best Pract Res Clin Gastroenterol 2006;20:633-49.
  • 3 Kajitani T. The general rules for the gastric cancer study in surgery and pathology. Part I. Clinical classification. Jpn J Surg 1981;11:127-39.
  • 4 Bonenkamp JJ, Songun I, Hermans J, Sasako M, Welvaart K, Plukker JT, et al. Randomised comparison of morbidity after D1 and D2 dissection for gastric cancer in 996 Dutch patients. Lancet 1995;345:745-8.
  • 5 Cuschieri A, Fayers P, Fielding J, Craven J, Bancewicz J, Joypaul V, et al. Postoperative morbidity and mortality after D1 and D2 resections for gastric cancer: Preliminary results of the MRC randomised controlled surgical trial. The Surgical Cooperative Group. Lancet 1996;347:995-9.
  • 6 Biffi R, Chiappa A, Luca F, Pozzi S, Lo Faso F, Cenciarelli S, et al. Extended lymph node dissection without routine spleno-pancreatectomy for treatment of gastric cancer: Low morbidity and mortality rates in a single center series of 250 patients. J Surg Oncol 2006;93:394-400.
  • 7 Songun I, Putter H, Kranenbarg EM, Sasako M, van de Velde CJ. Surgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D1D2 trial. Lancet Oncol 2010;11:439-49.
  • 8 Roviello F, Marrelli D, Morgagni P, de Manzoni G, Di Leo A, Vindigni C, et al. Survival benefit of extended D2 lymphadenectomy in gastric cancer with involvement of second level lymph nodes: A longitudinal multicenter study. Ann Surg Oncol 2002;9:894-900.
  • 9 Degiuli M, Sasako M, Ponti A, Soldati T, Danese F, Calvo F. Morbidity and mortality after D2 gastrectomy for gastric cancer: Results of the Italian Gastric Cancer Study Group prospective multicenter surgical study. J Clin Oncol 1998;16:1490-3.
  • 10 Degiuli M, Sasako M, Calgaro M, Garino M, Rebecchi F, Mineccia M, et al. Morbidity and mortality after D1 and D2 gastrectomy for cancer: Interim analysis of the Italian Gastric Cancer Study Group (IGCSG) randomised surgical trial. Eur J Surg Oncol 2004;30:303-8.
  • 11 Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 2006;355:11-20.
  • 12 Smalley SR, Benedetti JK, Haller DG, Hundahl SA, Estes NC, Ajani JA, et al. Updated analysis of SWOG-directed intergroup study 0116: A phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection. J Clin Oncol 2012;30:2327-33.
  • 13 Sasako M, Sakuramoto S, Katai H, Kinoshita T, Furukawa H, Yamaguchi T, et al. Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. J Clin Oncol 2011;29:4387-93.
  • 14 Bang YJ, Kim YW, Yang HK, Chung HC, Park YK, Lee KH, et al. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): A phase 3 open-label, randomised controlled trial. Lancet 2012;379:315-21.
  • 15 Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med 2008;358:36-46.
  • 16 Thuss-Patience PC, Kretzschmar A, Bichev D, Deist T, Hinke A, Breithaupt K, et al. Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer - A randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer 2011;47:2306-14.
  • 17 Ford HE, Marshall A, Bridgewater JA, Janowitz T, Coxon FY, Wadsley J, et al. COUGAR-02 Investigators. Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial. Lancet Oncol. 2014;15:78-86. doi: 10.1016/S1470-2045(13)70549-7 [Epub 2013 Dec 10].
  • 18 Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): A phase 3, open-label, randomised controlled trial. Lancet 2010;376:687-97.
  • 19 Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): An international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet 2014;383:31-9.
  • 20 Wilke H, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, et al. RAINBOW: A global, phase III, randomized, double-blind study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in the treatment of metastatic gastroesophageal junction (GEJ) and gastric adenocarcinoma following disease progression on first-line platinum- and fluoropyrimidine-containing combination therapy rainbow IMCL CP12-0922 (I4T-IE-JVBE). J Clin Oncol 2014; 32 (3_suppl): LBA7.
  • 21 Nashimoto A, Nakajima T, Furukawa H, Kitamura M, Kinoshita T, Yamamura Y, et al. Randomized trial of adjuvant chemotherapy with mitomycin, fluorouracil, and cytosine arabinoside followed by oral fluorouracil in serosa-negative gastric cancer: Japan Clinical Oncology Group 9206-1. J Clin Oncol 2003;21:2282-7.
  • 22 Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 2001;345:725-30.
  • 23 Wang J, Sun Y, Bertagnolli MM. Comparison of gastric cancer survival between Caucasian and Asian patients treated in the United States: Results from the Surveillance Epidemiology and End Results (SEER) Database. Ann Surg Oncol DOI 10.1245/s10434-015-4388-4.
  • 24 Heidelberger C, Chaudhuri NK, Danneberg P, Mooren D, Griesbach L, Duschinsky R, et al. Fluorinated pyrimidines, a new class of tumour-inhibitory compounds. Nature 1957; 179:663-6.
  • 25 Saif MW, Syrigos KN, Katirtzoglou NA. S-1: A promising new oral fluoropyrimidine derivative. Expert Opin Investig Drugs 2009;18:335-48.
  • 26 Okeda R, Shibutani M, Matsuo T, Kuroiwa T, Shimokawa R, Tajima T. Experimental neurotoxicity of 5-fluorouracil and its derivatives is due to poisoning by the monofluorinated organic metabolites, monofluoroacetic acid and alpha-fluoro-beta-alanine. Acta Neuropathol 1990;81:66-73.
  • 27 Matsubara I, Kamiya J, Imai S. Cardiotoxic effects of 5-fluorouracil in the guinea pig. Jpn J Pharmacol 1980; 30:871-9.
  • 28 Meta-analysis Group in Cancer, Piedbois P, Rougier P, Buyse M, Pignon J, Ryan L, et al. Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer. J Clin Oncol 1998;16:301-8.
  • 29 Au JL, Wu AT, Friedman MA, Sadée W. Pharmacokinetics and metabolism of ftorafur in man. Cancer Treat Rep 1979;63:343-50.
  • 30 Baker SD, Khor SP, Adjei AA, Doucette M, Spector T, Donehower RC, et al. Pharmacokinetic, oral bioavailability, and safety study of fluorouracil in patients treated with 776C85, an inactivator of dihydropyrimidine dehydrogenase. J Clin Oncol 1996;14:3085-96.
  • 31 Cao S, Rustum YM, Spector T. 5-Ethynyluracil (776C85): Modulation of 5-fluorouracil efficacy and therapeutic index in rats bearing advanced colorectal carcinoma. Cancer Res 1994;54:1507-10.
  • 32 Toide H, Akiyoshi H, Minato Y, Okuda H, Fujii S. Comparative studies on the metabolism of 2-(tetrahydrofuryl)-5-fluorouracil and 5-fluorouracil. Gan 1977;68:553-60.
  • 33 El Sayed YM, Sadée W. Metabolic activation of R,S-1-(tetrahydro-2-furanyl)-5-fluorouracil (ftorafur) to 5-fluorouracil by soluble enzymes. Cancer Res 1983;43:4039-44.
  • 34 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;78:748-55.
  • 35 Shirasaka T, Shimamoto Y, Fukushima M. Inhibition by oxonic acid of gastrointestinal toxicity of 5-fluorouracil without loss of its antitumor activity in rats. Cancer Res 1993;53:4004-9.
  • 36 Shirasaka T, Shimamato Y, Ohshimo H, Yamaguchi M, Kato T, Yonekura K, et al. Development of a novel form of an oral 5-fluorouracil derivative (S-1) directed to the potentiation of the tumor selective cytotoxicity of 5-fluorouracil by two biochemical modulators. Anticancer Drugs 1996;7:548-57.
  • 37 Taguchi T, Inuyama Y, Kanamaru R, Hasegawa K, Akazawa S, Niitani H, et al. Phase I study of S-1. S-1 Study Group. Gan To Kagaku Ryoho 1997;24:2253-64.
  • 38 Chu QS, Hammond LA, Schwartz G, Ochoa L, Rha SY, Denis L, et al. Phase I and pharmacokinetic study of the oral fluoropyrimidine S-1 on a once-daily-for-28-day schedule in patients with advanced malignancies. Clin Cancer Res 2004;10:4913-21.
  • 39 Hoff PM, Saad ED, Ajani JA, Lassere Y, Wenske C, Medgyesy D, et al. Phase I study with pharmacokinetics of S-1 on an oral daily schedule for 28 days in patients with solid tumors. Clin Cancer Res 2003;9:134-42.
  • 40 Baba H, Ohtsu A, Sakata Y, Mitachi Y, Sugimachi K, Taguchi T. Late phase II study of S-1 in patients with advanced colorectal cancer in Japan. Proc Am Soc Clin Oncol 1998;17:277A.
  • 41 Ohtsu A, Sakata Y, Horikoshi N, Mitachi Y, Sugimachi D, Taguchi T. A phase II study of S-1 in patients with advanced gastric cancer. Proc Am Soc Clin Oncol 1998;17:262A.
  • 42 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;25:1151-8.
  • 43 Lordick F, Jäger D. Current status and future of chemotherapy and biochemotherapy in gastroesophageal cancers. Gastrointest Cancer Res 2008;2:187-97.
  • 44 Moynihan T, Hansen R, Anderson T, Quebbeman E, Beatty P, Ausman R, et al. Continuous 5-fluorouracil infusion in advanced gastric carcinoma. Am J Clin Oncol 1988;11: 461-4.
  • 45 Hong YS, Song SY, Lee SI, Chung HC, Choi SH, Noh SH, et al. A phase II trial of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer. Ann Oncol 2004;15:1344-7.
  • 46 Koizumi W, Kurihara M, Nakano S, Hasegawa K. Phase II study of S-1, a novel oral derivative of 5-fluorouracil, in advanced gastric cancer. For the S-1 Cooperative Gastric Cancer Study Group. Oncology 2000;58:191-7.
  • 47 Sakata Y, Ohtsu A, Horikoshi N, Sugimachi K, Mitachi Y, Taguchi T. Late phase II study of novel oral fluoropyrimidine anticancer drug S-1 (1 M tegafur-0.4 M gimestat-1 M otastat potassium) in advanced gastric cancer patients. Eur J Cancer 1998;34:1715-20.
  • 48 Miyazaki I, Kawai T, Harada Y, Moriyasu F. A predictive factor for the response to S-1 plus cisplatin in gastric cancer. World J Gastroenterol 2010;16:4575-82.
  • 49 Lee SR, Kim HO, Yoo CH. Clinical outcomes of TS-1 chemotherapy for advanced and recurrent gastric cancer. J Korean Surg Soc 2011;81:163-8.
  • 50 Boku N, Yamamoto S, Shirao K, Doi T, Sawaki A, Koizumi W, et al. Gastrointestinal Oncology Study Group/Japan Clinical Oncology Group. Randomized phase III study of 5-fluorouracil (5-FU) alone versus combination of irinotecan and cisplatin (CP) versus S-1 alone in advanced gastric cancer (JCOG9912). Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings (Post-Meeting Edition). 2007;25 (June 20 Supplement), LBA4513.
  • 51 Koizumi W, Tanabe S, Saigenji K, Ohtsu A, Boku N, Nagashima F, et al. Phase I/II study of S-1 combined with cisplatin in patients with advanced gastric cancer. Br J Cancer 2003;89:2207-12.
  • 52 Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, et al. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): A phase III trial. Lancet Oncol 2008;9:215-21.
  • 53 Narahara H, Iishi H, Imamura H, Tsuburaya A, Chin K, Imamoto H, et al. Randomized phase III study comparing the efficacy and safety of irinotecan plus S-1 with S-1 alone as first-line treatment for advanced gastric cancer (study GC0301/TOP-002). Gastric Cancer 2011;14:72-80.
  • 54 Kim Y, Koizumi W, Lee K, Kishimoto T, Chung H, et al. Randomized phase III study of S-1 alone versus S-1 plus docetaxel (DOC) in the treatment for advanced gastric cancer (AGC): The START trial. J Clin Oncol 2011;29(Suppl 4):7-10. doi:10.1200/JCO.2010.32.3022. PubMed: 21115871.
  • 55 Yamada Y, Higuchi K, Nishikawa K, Gotoh M, Fuse N, Sugimoto N, et al. Phase III study comparing oxaliplatin plus S-1 with cisplatin plus S-1 in chemotherapy-naïve patients with advanced gastric cancer. Ann Oncol 2015;26:141-8.
  • 56 Shitara K, Morita S, Fujitani K, Kadowaki S, Takiguchi N, Hirabayashi N, et al. Combination chemotherapy with S-1 plus cisplatin for gastric cancer that recurs after adjuvant chemotherapy with S-1: Multi-institutional retrospective analysis. Gastric Cancer 2012;15:245-51.
  • 57 Lv F, Liu X, Wang B, Guo H, Li J, Shen L, et al. S-1 monotherapy as second line chemotherapy in advanced gastric cancer patients previously treated with cisplatin/infusional fluorouracil. Int J Clin Exp Pathol 2014;7:4274-9.
  • 58 Ajani JA, Faust J, Ikeda K, Yao JC, Anbe H, Carr KL, et al. Phase I pharmacokinetic study of S-1 plus cisplatin in patients with advanced gastric carcinoma. J Clin Oncol 2005;23:6957-65.
  • 59 Lenz HJ, Lee FC, Haller DG, Singh D, Benson AB 3 rd , Strumberg D, et al. Extended safety and efficacy data on S-1 plus cisplatin in patients with untreated, advanced gastric carcinoma in a multicenter phase II study. Cancer 2007;109:33-40.
  • 60 Ajani JA, Rodriguez W, Bodoky G, Moiseyenko V, Lichinitser M, Gorbunova V, et al. Multicenter phase III comparison of cisplatin/S-1 with cisplatin/infusional fluorouracil in advanced gastric or gastroesophageal adenocarcinoma study: The FLAGS trial. J Clin Oncol 2010;28:1547-53.
  • 61 Kurokawa Y, Sugimoto N, Miwa H, Tsuda M, Nishina S, Okuda H, et al. Phase II study of trastuzumab in combination with S-1 plus cisplatin in HER2-positive gastric cancer (HERBIS-1). Br J Cancer 2014;110:1163-8.
  • 62 Yang J, Zhou Y, Min K, Yao Q, Xu CN. S-1-based vs non-S-1-based chemotherapy in advanced gastric cancer: A meta-analysis. World J Gastroenterol 2014;20:11886-93.
  • 63 Takahari D, Hamaguchi T, Yoshimura K, Katai H, Ito S, Fuse N, et al. Feasibility study of adjuvant chemotherapy with S-1 plus cisplatin for gastric cancer. Cancer Chemother Pharmacol 2011;67:1423-8.
  • 64 Tamura S, Fujitani K, Kimura Y, Tsuji T, Matsuyama J, Iijima S, et al. Phase II feasibility study of adjuvant S-1 plus docetaxel for stage III gastric cancer patients after curative D2 gastrectomy. Oncology 2011;80:296-300.
  • 65 Yang L, Yang Y, Qin Q, Zhou A, Zhao J, Wang J, et al. Dose-finding study on adjuvant chemotherapy with S-1 plus oxaliplatin for gastric cancer. Mol Clin Oncol 2014;2:93-98.
  • 66 Takahari D, Hamaguchi T, Yoshimura K, Katai H, Ito S, Fuse N, et al. Survival analysis of adjuvant chemotherapy with S-1 plus cisplatin for stage III gastric cancer. Gastric Cancer 2014;17:383-6.
  • 67 Fujitani K, Tamura S, Kimura Y, Tsuji T, Matsuyama J, Iijima S, et al. Three-year outcomes of a phase II study of adjuvant chemotherapy with S-1 plus docetaxel for stage III gastric cancer after curative D2 gastrectomy. Gastric Cancer 2014;17:348-53.
  • 68 Egawa T, Kemmochi T, Irino T, Mihara K, Okamura A, Etoh E, et al. Adjuvant chemotherapy with S-1 plus docetaxel for highly advanced gastric cancer patients. Gan To Kagaku Ryoho 2012;39:2310-2.
  • 69 Tsuburaya A, Yoshida K, Kobayashi M, Yoshino S, Takahashi M, Takiguchi N, et al. Sequential paclitaxel followed by tegafur and uracil (UFT) or S-1 versus UFT or S-1 monotherapy as adjuvant chemotherapy for T4a/b gastric cancer (SAMIT): A phase 3 factorial randomised controlled trial. Lancet Oncol 2014;15:886-93.
  • 70 Aoyama T, Yoshikawa T, Watanabe T, Hayashi T, Ogata T, Cho H, et al. Macroscopic tumor size as an independent prognostic factor for stage II/III gastric cancer patients who underwent D2 gastrectomy followed by adjuvant chemotherapy with S-1. Gastric Cancer 2011;14:274-8.
  • 71 Ema A, Yamashita K, Sakuramoto S, Wang G, Mieno H, Nemoto M, et al. Lymph node ratio is a critical prognostic predictor in gastric cancer treated with S-1 chemotherapy. Gastric Cancer 2014;17:67-75.
  • 72 Sakurai Y, Kamoshida S, Furuta S, Sunagawa R, Inaba K, Isogaki J, et al. Predictive value of orotate phosphoribosyltransferase in chemoresistant patients with gastric carcinoma who underwent S-1-based neoadjuvant/adjuvant chemotherapy. Gan To Kagaku Ryoho 2008;35:1147-55.
  • 73 Wada T, Kunisaki C, Hasegawa S, Takagawa R, Momiyama M, Kosaka T, et al. Factors predictive of recurrence after surgery for gastric cancer followed by adjuvant S-1 chemotherapy. Anticancer Res 2013;33:1747-51.
  • 74 Omura T, Shimada Y, Nagata T, Okumura T, Fukuoka J, Yamagishi F, et al. Relapse-associated microRNA in gastric cancer patients after S-1 adjuvant chemotherapy. Oncol Rep 2014;31:613-8.
  • 75 McCulloch PG, Ochiai A, O′Dowd GM, Nash JR, Sasako M, Hirohashi S. Comparison of the molecular genetics of c-erb-B2 and p53 expression in stomach cancer in Britain and Japan. Cancer 1995;75:920-5.
  • 76 Bonenkamp JJ, van de Velde CJ, Kampschöer GH, Hermans J, Hermanek P, Bemelmans M, et al. Comparison of factors influencing the prognosis of Japanese, German, and Dutch gastric cancer patients. World J Surg 1993;17:410-4.
  • 77 Yoshikawa T, Tanabe K, Nishikawa K, Ito Y, Matsui T, Kimura Y, et al. Induction of a pathological complete response by four courses of neoadjuvant chemotherapy for gastric cancer: Early results of the randomized phase II COMPASS trial. Ann Surg Oncol 2014;21:213-9.
  • 78 Okabe H, Ueda S, Obama K, Hosogi H, Sakai Y. Induction chemotherapy with S-1 plus cisplatin followed by surgery for treatment of gastric cancer with peritoneal dissemination. Ann Surg Oncol 2009;16:3227-36.
  • 79 Li T, Chen L. Efficacy and safety of SOX regimen as neoadjuvant chemotherapy for advanced gastric cancer. Zhonghua Wei Chang Wai Ke Za Zhi 2011;14:104-6.
  • 80 Oyama K, Fushida S, Kinoshita J, Makino I, Nakamura K, Hayashi H, et al. Efficacy of pre-operative chemotherapy with docetaxel, cisplatin, and S-1 (DCS therapy) and curative resection for gastric cancer with pathologically positive para-aortic lymph nodes. J Surg Oncol 2012;105:535-41.
  • 81 Nagahama T, Ando M, Seki R, Fujiya K, Amagasa H, Takasaki J, et al. Preoperative chemotherapy for advanced gastric cancer. Gan To Kagaku Ryoho 2013;40:2217-9.
  • 82 Inoue T, Yachida S, Usuki H, Kimura T, Hagiike M, Okano K, et al. Pilot feasibility study of neoadjuvant chemoradiotherapy with S-1 in patients with locally advanced gastric cancer featuring adjacent tissue invasion or JGCA bulky N2 lymph node metastases. Ann Surg Oncol 2012;19:2937-45.
  • 83 Matsuda S, Takahashi T, Fukada J, Fukuda K, Kawakubo H, Saikawa Y, et al. Phase I study of neoadjuvant chemoradiotherapy with S-1 plus biweekly cisplatin for advanced gastric cancer patients with lymph node metastasis: -KOGC04-. Radiat Oncol 2014;9:9.
  • 84 Hirata K, Horikoshi N, Aiba K, Okazaki M, Denno R, Sasaki K, et al. Pharmacokinetic study of S-1, a novel oral fluorouracil antitumor drug. Clin Cancer Res 1999;5:2000-5.
  • 85 van Groeningen CJ, Peters GJ, Schornagel JH, Gall H, Noordhuis P, de Vries MJ, et al. Phase I clinical and pharmacokinetic study of oral S-1 in patients with advanced solid tumors. J Clin Oncol 2000;18:2772-9.
  • 86 Cohen SJ, Leichman CG, Yeslow G, Beard M, Proefrock A, Roedig B, et al. Phase I and pharmacokinetic study of once daily oral administration of S-1 in patients with advanced cancer. Clin Cancer Res 2002;8:2116-22.
  • 87 Yoshida R, Nakajima M, Nishimura K, Tokudome S, Kwon JT, Yokoi T. Effects of polymorphism in promoter region of human CYP2A6 gene (CYP2A6FNx019) on expression level of messenger ribonucleic acid and enzymatic activity in vivo and in vitro. Clin Pharmacol Ther 2003;74:69-76.
  • 88 Yoshida K, Hirabayashi N, Takiyama W, Ninomiya M, Takakura N, Sakamoto J, et al. Phase I study of combination therapy with S-1 and docetaxel (TXT) for advanced or recurrent gastric cancer. Anticancer Res 2004;24:1843-52.
  • 89 Hokita S, Aikou T, Miyazono F, Ishigami S, Aridome K, Maenohara S, et al. A phase I combination chemotherapy study of biweekly paclitaxel and S-1 administration in patients with advanced gastric cancer. Cancer Chemother Pharmacol 2006;57:736-40.
  • 90 Peters GJ, Noordhuis P, Van Groeningen CJ, Giaccone G, Holwerda U, Voorn D, et al. The effect of food on the pharmacokinetics of S-1 after single oral administration to patients with solid tumors. Clin Cancer Res 2004;10:4072-6.
  • 91 Chou WC, Chang CL, Liu KH, Hsu JT, Cheng WH, Hsu HC, et al. Total gastrectomy increases the incidence of grade III and IV toxicities in patients with gastric cancer receiving adjuvant TS-1 treatment. World J Surg Oncol 2013;11:287.
  • 92 Aoyama T, Yoshikawa T, Hayashi T, Kuwabara H, Mikayama Y, Ogata T, et al. Risk factors for 6-month continuation of S-1 adjuvant chemotherapy for gastric cancer. Gastric Cancer 2013;16:133-9.