Skip to main content
SpringerLink
Log in

5-year follow-up results of a JCOG1104 (OPAS-1) phase III non-inferiority trial to compare 4 courses and 8 courses of S-1 adjuvant chemotherapy for pathological stage II gastric cancer

  • Original Article
  • Published:
Gastric Cancer Aims and scope Submit manuscript

A Letter to the Editor to this article was published on 11 April 2024

Abstract

Background

Postoperative adjuvant chemotherapy with S-1 for 1 year (corresponding to eight courses) is the standard treatment for pathological stage II gastric cancer. The phase III trial (JCOG1104) investigating the non-inferiority of four courses of S-1 to eight courses was terminated due to futility at the first interim analysis. To confirm the primary results, we reported the results after a 5-years follow-up in JCOG1104.

Methods

Patients histologically diagnosed with stage II gastric cancer after radical gastrectomy were randomly assigned to receive S-1 for eight or four courses. In detail, 80 mg/m2/day S-1 was administered for 4 weeks followed by a 2-week rest as a single course.

Results

Between February 16, 2012, and March 19, 2017, 590 patients were enrolled and randomly assigned to 8-course (295 patients) and 4-course (295 patients) regimens. After a 5-years follow-up, the relapse-free survival at 3 years was 92.2% for the 8-course arm and 90.1% for the 4-course arm, and that at 5 years was 87.7% for the 8-course arm and 85.6% for the 4-course arm (hazard ratio 1.265, 95% CI 0.846–1.892). The overall survival at 3 years was 94.9% for the 8-course arm, 93.2% for the 4-course arm, and that at 5 years was 89.7% for the 8-course arm, and 88.6% for the 4-course arm (HR 1.121, 95% CI 0.719–1.749).

Conclusions

The survival of the four-course arm was slightly but consistently inferior to that of the eight-course arm. Eight-course S-1 should thus remain the standard adjuvant chemotherapy for pathological stage II gastric cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.

    Article  PubMed  Google Scholar 

  2. Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, Furukawa H, Nakajima T, Ohashi Y, Imamura H, et al. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007;357(18):1810–20.

    Article  CAS  PubMed  Google Scholar 

  3. Sasako M, Sakuramoto S, Katai H, Kinoshita T, Furukawa H, Yamaguchi T, Nashimoto A, Fujii M, Nakajima T, Ohashi Y. 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(33):4387–93.

    Article  CAS  PubMed  Google Scholar 

  4. Japanese gastric cancer a: Japanese gastric cancer treatment guidelines 2021 (6th edition). Gastric Cancer 2023;26(1):1–25.

  5. Yoshikawa T, Terashima M, Mizusawa J, Nunobe S, Nishida Y, Yamada T, Kaji M, Fukushima N, Hato S, Choda Y, et al. Four courses versus eight courses of adjuvant S-1 for patients with stage II gastric cancer (JCOG1104 [OPAS-1]): an open-label, phase 3, non-inferiority, randomised trial. Lancet Gastroenterol Hepatol. 2019;4(3):208–16.

    Article  PubMed  Google Scholar 

  6. Japanese gastric cancer a: Japanese classification of gastric carcinoma: 3rd English edition. Gastric Cancer 2011;14(2):101–12.

  7. Lan KKG, DeMets D. Discrete sequential boundaries for clinical trials. Biometrika. 1983;70:659.

    Article  Google Scholar 

  8. Fleming TR, Sharples K, McCall J, Moore A, Rodgers A, Stewart R. Maintaining confidentiality of interim data to enhance trial integrity and credibility. Clin Trials. 2008;5(2):157–67.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Kakeji Y, Ishikawa T, Suzuki S, Akazawa K, Irino T, Miyashiro I, Ono H, Suzuki H, Tanabe S, Kadowaki S, et al. A retrospective 5-year survival analysis of surgically resected gastric cancer cases from the Japanese Gastric Cancer Association nationwide registry (2001–2013). Gastric Cancer. 2022;25(6):1082–93.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Megumi Miyazawa, Kumiko Yanagida, Harumi Kaba for data management. The study was supported in part by the National Cancer Center Research and Development Funds (23-A-16, 23-A-19, 26-A-4, 29-A-3, 2020-J-3, 2023-J-03) and by AMED under Grant Number JP17ck0106322. Participating Institutions (59 institutions) are Hakodate Goryoukaku Hospital, Keiyukai Sapporo Hospital, Iwate Medical University, National Hospital Organization, Sendai Medical Center, Miyagi Cancer Center, Yamagata Prefectural Central Hospital, Tochigi Cancer Center, National Defense Medical College, Saitama Cancer Center, Saitama Medical University International Medical Center, National Cancer Center Hospital East, Chiba Cancer Center, National Cancer Center Hospital, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, Tokyo Medical and Dental University Hospital, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Toranomon Hospital, Tokyo Metropolitan Bokutoh Hospital, Kanagawa Cancer Center, Kitasato University School of Medicine, Yokohama City University Medical Center, Niigata Cancer Center Hospital, Nagaoka Chuo General Hospital, Toyama Prefectural Central Hospital, Ishikawa Prefectural Central Hospital, Gifu University School of Medicine, Gifu Municipal Hospital, Shizuoka General Hospital, Shizuoka Cancer Center, Aichi Cancer Center Hospital, Nagoya University School of Medicine, National Hospital Organization Kyoto Medical Center, Kyoto Second Red Cross Hospital, Osaka University Graduate School of Medicine, Kindai University Faculty of Medicine, Osaka International Cancer Institute, Osaka National Hospital, Osaka General Medical Center, Osaka Medical College, Toyonaka Municipal Hospital, Sakai City Medical Center, Kansai Medical University Hospital, Osaka Rosai Hospital, Kobe University Graduate School of Medicine, Kansai Rosai Hospital, Hyogo College of Medicine, Hyogo Cancer Center, Itami City Hospital, Tenri Hospital, Wakayama Medical University, School of Medicine, Shimane University Faculty of Medicine, Okayama University Hospital, Hiroshima University Hospital, Hiroshima City Hospital, Hiroshima City Asa Hospital, Fukuyama City Hospital, Tokushima Red Cross Hospital, National Hospital Organization Shikoku Cancer Center, Oita University Faculty of Medicine. Please see the appendix including each site from which patients were recruited, the name of principal investigator responsible for this site, and the number of patients which were recruited from that particular site.

Funding

The study was supported by the Japan Agency for Medical Research and Development, the Ministry of Health, Labour and Welfare of Japan, and the National Cancer Center Research and Development Fund.

Author information

Authors and Affiliations

  1. Department of Gastric Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan

    Takaki Yoshikawa

  2. Division of Gastric Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-Cho, Sunto-Gun, Shizuoka Prefecture, 411-8777, Japan

    Masanori Terashima

  3. JCOG Data Center/Operations Office, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan

    Junki Mizusawa, Hiroshi Katayama & Haruhiko Fukuda

  4. Gastroenterological Surgery, Cancer Institute Ariake Hospital, 3-8-31 Ariake, Koto-Ku, Tokyo, 135-8550, Japan

    Souya Nunobe & Takeshi Sano

  5. Department of Surgery, Keiyukai Sapporo Hospital, Kita 1-1, Hondori 14, Shiroishi-Ku, Sapporo, 003-0027, Japan

    Yasunori Nishida

  6. Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-Ku, Yokohama, 241-8515, Japan

    Takanobu Yamada

  7. Department of Surgery, Toyama Prefectural Central Hospital, Nishinagae 2-2-78, Toyama, 930-8550, Japan

    Masahide Kaji

  8. Department of Surgery, Yamagata Prefectural Central Hospital, Aoyanagi 1800, Yamagata, 990-2292, Japan

    Takashi Nomura

  9. Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center, 160 Kou, Minami-Umemotomachi, Matsuyama, 791-0280, Japan

    Shinji Hato

  10. Department of Surgery, Hiroshima City Hiroshima Citizens Hospital, 7-33 Motomachi, Naka-Ku, Hiroshima, 730-8518, Japan

    Yasuhiro Choda

  11. Department of Digestive Surgery, Niigata Cancer Center Hospital, Kawagishimachi, Chuo-Ku, Niigata, 951-8566, Japan

    Hiroshi Yabusaki

  12. Department of Gastroenterological Surgery and Pediatric Surgery, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu City, 501-1193, Japan

    Kazuhiro Yoshida

  13. Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-Ku, Nagoya, 464-8681, Japan

    Kazunari Misawa

  14. Department of Surgery, Kansai Rosai Hospital, Inabaso 3-1-69, Amagasaki, 660-8511, Japan

    Toru Masuzawa

  15. Department of Gastroenterological Oncology, Hyogo Cancer Center, Kitaouji-Cho 13-70, Akashi, 673-8558, Japan

    Masahiro Tsuda

  16. Department of Surgery, Nagaoka Chuo General Hospital, 2041 Kawasakimachi, Nagaoka, 940-8653, Japan

    Yasuyuki Kawachi

  17. Department of Gastroenterological Surgery, Osaka University, 2-2 Yamadaoka, Suita, 565-0871, Japan

    Yukinori Kurokawa

  18. Department of Oncology and General Medicine, Institute of Medical Science, IMSUT Hospital, University of Tokyo, 4-6-1, Shiroganedai, Mitato-Ku, Tokyo, 108-8639, Japan

    Narikazu Boku

  19. Department of Multidisciplinary Surgical Oncology, Hyogo College of Medicine, Mukogawacho 1-1, Nishinomiya, 663-8131, Japan

    Mitsuru Sasako

Authors
  1. Takaki Yoshikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masanori Terashima
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Junki Mizusawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Souya Nunobe
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yasunori Nishida
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Takanobu Yamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Masahide Kaji
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Takashi Nomura
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Shinji Hato
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yasuhiro Choda
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Hiroshi Yabusaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Kazuhiro Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Kazunari Misawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Toru Masuzawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Masahiro Tsuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Yasuyuki Kawachi
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Hiroshi Katayama
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Haruhiko Fukuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Yukinori Kurokawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Narikazu Boku
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Takeshi Sano
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Mitsuru Sasako
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

TYo, MS, and TS had the original idea for the study, and MS followed by MTer chaired the study group. TYo wrote the protocol, assisted by MTer, JM, HK, HF, TS, and MS. Statistical analyses were performed by JM. All the authors except JM, HK, and HF recruited patients into the study. JM, HK, and HF were responsible for data management, statistical analysis, and interpretation. TYo drafted the paper. MTer, JM, HK, HF, NB, TS, and MS revised the paper. All the authors reviewed the paper. All the authors approved the final version.

Corresponding author

Correspondence to Takaki Yoshikawa.

Ethics declarations

Conflict of interest

TYo had received grants from Japan Agency for Medical Research and Development (AMED) and The National Cancer Center Research and Development Fund during the conduct of the study and personal fees from Taiho Pharmaceutical, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol, MSD, Daiichi Sankyo, Nippon Kayaku, Terumo, Otsuka, AstraZeneca, Pfizer, Daiichi Sankyo, Johnson and Johnson, Medtronic Japan, Intuitive Japan, and Olympus. MTer had received grants from Japan Agency for Medical Research and Development (AMED) and The National Cancer Center Research and Development Fund during the conduct of the study and personal fees from Taiho Pharmaceutical, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol, MSD, Daiichi Sankyo, Nippon Kayaku, Eli Lilly, Pfizer, Daiichi Sankyo, Johnson and Johnson, Medtronic Japan, Intuitive Japan, and Olympus. JM had received grants from Ministry of Health, Labour and Welfare, Japan, grants from Japan Agency for Medical Research and Development (AMED) during the conduct of the study and personal fees from Taiho pharmaceutical and Chugai pharmaceutical; his spouse is an employee of Pfizer Japan Inc. SN had no conflict of interest. YN had no conflict of interest. TYma had received personal fee from Taiho and Johnson & Johnson. KM had no conflict of interest. TN had no conflict of interest. SH had no conflict of interest. YC had received personal fee from ONO and Bristol-Myers Squibb. HY had had no conflict of interest. KY had received personal fee from Abbott. Asahi Kasei Pharma, Chugai Pharma, Covidien, Daiichi Sankyo, Eisai, Eli Lilly, Johnson & Johnson, Kaken Pharm, Kyowa Kirin, Nippon Kayaku, Otsuka Pharm, Sanofi, Taiho, Takeda, TERUMO, Tsumura, and Yakult Honsya. KM had no conflict of interest. TM had no conflict of interest. MTsu had no conflict of interest. YKaw had no conflict of interest. HK had received grants from Ministry of Health, Labour and Welfare, Japan and from Japan Agency for Medical Research and Development (AMED). HF had received personal fee from Kyowa Kirin, Chuigai Parm and CMIC. YKur had received personal fee from Taiho, NB had received personal fee from Taiho, Ono, Bristol-Myers Squibb, Daiichi Sankyo, and Eli Lilly. TS had received personal fee from Taiho and Chugai. MS had received personal fee from Taiho, Chugai, and Yakult.

Human rights statement and informed consent

All the procedures were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the 1964 Declaration of Helsinki and later versions. Informed consent for inclusion in the study was obtained from all the patients.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

10120_2023_1447_MOESM1_ESM.pdf

Supplementary Fig. 1: A Analysis using the unaffected population (RFS, n = 513). B Analysis using the unaffected population (OS, n = 513); Supplementary Fig. 2: Cumulative incidence curve of recurrence (PDF 12360 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yoshikawa, T., Terashima, M., Mizusawa, J. et al. 5-year follow-up results of a JCOG1104 (OPAS-1) phase III non-inferiority trial to compare 4 courses and 8 courses of S-1 adjuvant chemotherapy for pathological stage II gastric cancer. Gastric Cancer 27, 155–163 (2024). https://doi.org/10.1007/s10120-023-01447-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10120-023-01447-5

Keywords

Search

Navigation