Medical Oncology

, Volume 28, Issue 4, pp 1004–1011 | Cite as

S-1-based therapy versus 5-FU-based therapy in advanced gastric cancer: a meta-analysis

  • Jiahao Huang
  • Yunfei CaoEmail author
  • Liucheng Wu
  • Cun Liao
  • Yongming He
  • Feng GaoEmail author
Original Paper


We set out to evaluate the efficacy and safety of S-1-based therapy versus fluorouracil (5-FU)-based therapy in advanced gastric cancer (AGC). Eligible studies were identified from Pubmed, EMBASE, and Cochrane Library. Additionally, abstracts presented at American Society of Clinical Oncology (ASCO) conferences held between January 2000 and November 2009 were searched to identify relevant clinical trials. The outcome included overall survival (OS), overall response rate (ORR), and grade 3/4 advent events. Four randomized controlled trials (one full text and three abstracts) with 2,115 participants in AGC were identified in our analysis(1,065 patients were in the S-1-based group, 1,050 patients were in the 5-FU-based group). Meta-analysis showed there was significant OS benefit in favor of S-1-based therapy (hazard ratio [HR] = 0.87, 95% confidence interval [CI]: 0.79 to 0.96). Pooled estimate for ORR showed no significant difference between S-1-based group and 5-FU-based group (OR = 1.25, 95%CI: 0.31 to 5.09). Lower incidence of grade 3/4 neutropenia was observed in patients with S-1-based therapy (OR = 0.33, 95%CI: 0.25 to 0.44). With regard to grade 3/4 anemia (OR = 1.20, 95%CI: 0.74 to 1.96), leucopenia (OR = 1.09, 95%CI: 0.43 to 2.74), stomatitis (OR = 2.65, 95%CI: 0.12 to 58.89), diarrhea (OR = 0.53, 95% CI: 0.00 to 229.10), nausea (OR = 1.36, 95%CI: 0.68 to 2.72), and treatment-related deaths (OR = 1.84, 95%CI: 0.95 to 3.54), equivalent frequencies were found between groups. S-1-based therapy significantly improved OS in relation to 5-FU-based therapy. ORR and safety profile were considerable between two groups. These results needed to be confirmed by high-quality trials and further studies in the West.


S-1 5-FU Advanced gastric cancer Meta-analysis 


  1. 1.
    Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.PubMedCrossRefGoogle Scholar
  2. 2.
    Ries LAG, Melbert D,Krapcho M, Mariotto A, Miller BA, Feuer EJ et al. SEER Cancer Statistics Review, 1975–2004. National Cancer Institute: Bethesda, MD based on November 2006 SEER data submission, 2007.
  3. 3.
    Roukos DH. Extended lymphadenectomy in gastric cancer: when, for whom and why. Ann R Coll Surg Engl. 1998;80:16–24.PubMedGoogle Scholar
  4. 4.
    Roukos DH. Extended (D2) lymph node dissection for gastric cancer: do patients benefit? Ann Surg Onco. 2000;l7:253–5.CrossRefGoogle Scholar
  5. 5.
    Roukos DH, Hottenrott C, Encke A, Baltogiannis G, Casioumis D. Primary gastric lymphomas: a clinicopathologic study with literature review. Surg Oncol. 1994;3:115–25.PubMedCrossRefGoogle Scholar
  6. 6.
    Roukos DH. Early-stage gastric cancer: a highly treatable disease. Ann Surg Oncol. 2004;11:127–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Colorectal Cancer Collaborative Group. Palliative chemotherapy for advanced colorectal cancer: systematic review and meta-analysis. BMJ. 2000;321:531–5.CrossRefGoogle Scholar
  8. 8.
    Shirasaka T, Shimamoto 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.PubMedCrossRefGoogle Scholar
  9. 9.
    Sugimachi K, Maehara Y, Horikoshi N, Shimada Y, Sakata Y, Miyachi Y, et al. An early phase II study of oral S-1, a newly developed 5-fluorouracil derivative for advanced and recurrent gastrointestinal cancers. Oncology. 1999;57:202–10.PubMedCrossRefGoogle Scholar
  10. 10.
    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-04 M gimestat-1 M otastat potassium) in advanced gastric cancer patients. Eur J Cancer. 1998;34:1715–20.PubMedCrossRefGoogle Scholar
  11. 11.
    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. Oncology. 2000;58:191–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Higgins JPT, Green S (eds). Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.1 [updated September 2008]. The Cochrane Collaboration. 2008.Google Scholar
  13. 13.
    Hopewell S, Clarke M, Moher D, Clarke M, Moher D, Wager E. Consort for reporting randomized controlled trials in journal and conference abstracts: explanation and elaboration. PLoS Med. 2008;5:48–56.CrossRefGoogle Scholar
  14. 14.
    Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors: European Organization for research and treatment of cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92:205–16.PubMedCrossRefGoogle Scholar
  15. 15.
    Sutton AJ, Abrams KR, Jones DR, Sheldon TA, Song F. Methods for meta-analysis in medical research. Chichester: Wiley; 2000.Google Scholar
  16. 16.
    Yusuf S, Peto R, Jones DR, Collins R, Sleight P. Beta blockade during and after myocardial infarction: an overview of the randomized trials. Prog Cardiovasc Dis. 1985;27:335–71.PubMedCrossRefGoogle Scholar
  17. 17.
    Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088–101.PubMedCrossRefGoogle Scholar
  18. 18.
    Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.PubMedCrossRefGoogle Scholar
  19. 19.
    Boku N, Yamamoto S, Fukuda H, Shirao K, Doi T, Sawaki A, et al. Fluorouracil versus combination of irinotecan plus cisplatin versus S-1 in metastatic gastric cancer: a randomized phase 3 study. Lancet Oncol. 2009;10(11):1063–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Ajani JA, Rodriguez W, Bodoky G, Moiseyenko V, Lichinitser M, Gorbunova V et al. Multicenter phase III comparison of cisplatin/S-1 (CS) with cisplatin/5-FU (CF) as first-line therapy in patients with advanced gastric cancer (FLAGS) [abstract]. Gastrointestinal Cancers Symposium. 2009.Google Scholar
  21. 21.
    Fuse N, Fukuda H, Yamada Y, Sawaki A, Koizumi W, Suzuki Y, et al. Updated results of randomized phase III study of 5-fluorouracil (5-FU) alone versus combination of irinotecan, cisplatin (CP) versus S-1 alone in advanced gastric cancer (JCOG 9912) [abstract]. J Clin Oncol. 2009;27:15s.CrossRefGoogle Scholar
  22. 22.
    Jin M, Lu H, Li J, Shen L, Chen Z, Shi Y et al. Randomized 3-armed phase III study of S-1 monotherapy versus S-1/CDDP (SP) versus 5-FU/CDDP (FP) in patients (pts) with advanced gastric cancer (AGC): SC-101 study [abstract]. J Clin Oncol. 2008;26:4533.Google Scholar
  23. 23.
    Hoff PM, Saad ED, Ajani JA, Lassere Y, Wenske C, Medgyesy D. 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.PubMedGoogle Scholar
  24. 24.
    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.PubMedCrossRefGoogle Scholar
  25. 25.
    Wagner AD, Grothe W, Haerting J, Kleber G, Grothey A, Fleig WE. Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data. J Clin Oncol. 2006;24:2903–9.PubMedCrossRefGoogle Scholar
  26. 26.
    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.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Colorectal and Anal Surgery, First Affiliated HospitalGuangxi Medical UniversityNanningPeople’s Republic of China

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