Gastric Cancer

, Volume 22, Issue 5, pp 1044–1052 | Cite as

Randomized phase III trial of gastrectomy with or without neoadjuvant S-1 plus cisplatin for type 4 or large type 3 gastric cancer, the short-term safety and surgical results: Japan Clinical Oncology Group Study (JCOG0501)

  • Masanori TerashimaEmail author
  • Yoshiaki Iwasaki
  • Junki Mizusawa
  • Hiroshi Katayama
  • Kenichi Nakamura
  • Hitoshi Katai
  • Takaki Yoshikawa
  • Yuichi Ito
  • Masahide Kaji
  • Yutaka Kimura
  • Motohiro Hirao
  • Makoto Yamada
  • Akira Kurita
  • Masakazu Takagi
  • Narikazu Boku
  • Takeshi Sano
  • Mitsuru Sasako
  • Stomach Cancer Study Group, Japan Clinical Oncology Group
Original Article



The prognosis of patients with linitis plastica (type 4) and large (≥ 8 cm) ulcero-invasive-type (type 3) gastric cancer is extremely poor, even after extended surgery and adjuvant chemotherapy. Given the promising results of our previous phase II study evaluating neoadjuvant chemotherapy (NAC) with S-1 plus cisplatin (JCOG0210), we performed a phase III study to confirm the efficacy of NAC in these patients, with the safety and surgical results are presented here.


Eligible patients were randomized to gastrectomy plus adjuvant chemotherapy with S-1 (Arm A) or NAC followed by gastrectomy + adjuvant chemotherapy (Arm B). The primary endpoint was the overall survival (OS). This trial is registered at the UMIN Clinical Trials Registry as C000000279.


From February 2007 to July 2013, 300 patients were randomized (Arm A 149, Arm B 151). NAC was completed in 133 patients (88%). Major grade 3/4 adverse events during NAC were neutropenia (29.3%), nausea (5.4%), diarrhea (4.8%), and fatigue (2.7%). Gastrectomy was performed in 147 patients (99%) in Arm A and 139 patients (92%) in Arm B. The operation time was significantly shorter in Arm B than in Arm A (median 255 vs. 240 min, respectively; p = 0.024). There were no significant differences in Grade 2–4 morbidity and mortality (25.2% and 1.3% in Arm A and 15.8% and 0.7% in Arm B, respectively).


NAC for type 4 and large type 3 gastric cancer followed by D2 gastrectomy can be safely performed without increasing the morbidity or mortality.


Linitis plastica Neoadjuvant chemotherapy Large type 3 



The authors are grateful to the members of the JCOG Data Center and JCOG Operations Office for their support in this study.

Stomach Cancer Study Group, Japan Clinical Oncology Group: Akinori Takagane, Hakodate Goryokaku Hospital; Keisuke Koeda, Iwate Medical University; Shin Teshima, National Hospital Organization, Sendai Medical Center; Tsuneaki Fujitani, Miyagi Cancer Center; Norimasa Fukushima, Yamagata Prefectural Central Hospital; Naoyuki Matsushita, Tochigi Cancer Center; Hase Kazuo, National Defense Medical College; Yoshiyuki Kawashima, Saitama Cancer Center; Takahiro Kinoshita, National Cancer Center Hospital East; Hitoshi Katai, National Cancer Center Hospital; Yoshiaki Iwasaki, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital; Mikito Inokuchi, Tokyo Medical and Dental University Hospital; Takeshi Sano, Cancer Institute Hospital of Japanese Foundation for Cancer Research; Masanori Ueno, Toranomon Hospital; Ikuo Wada, Tokyo Metropolitan Bokutoh Hospital; Takaki Yoshikawa, Kanagawa Cancer Center; Hiroshi Yabusaki, Niigata Cancer Center Hospital; Yasuyuki Kawauchi, Nagaoka Chuo General Hospital; Kaoru Miyashita, Tsubame Rosai Hospital; Masahide Kaji, Toyama Prefectural Central Hospital; Makoto Yamada, Gifu Municipal Hospital; Masakazu Takagi, Shizuoka General Hospital; Masanori Terashima, Shizuoka Cancer Center; Seiji Ito, Aichi Cancer Center Hospital; Hiroaki Hata, National Hospital Organization Kyoto Medical Center Hiroki Taniguchi, Kyoto Second Red Cross Hospital; Yuichiro Doki, Osaka University Graduate School of Medicine; Takushi Yasuda, Kinki University Faculty of Medicine; Ken Omori, Osaka Prefectural Hospital Organization Osaka Medical Center for Cancer and Cardiovascular Diseases; Motohiro Hirao, National Hospital Organization Osaka National Hospital; Masahiro Goto, Osaka Medical College; Hiroshi Imamura, Toyonaka Municipal Hospital.


The study was supported in part by the National Cancer Center Research and Development Funds (23-A-19, and 26-A-4, 29-A-3) and a Grant-in-Aid for Clinical Cancer Research (H19-15, H22-027, H22-23) from the Ministry of Health, Labour and Welfare of Japan.

Compliance with ethical standards

Conflict of interest

Author MT has received personal fees from Taiho, Ono, Chugai, Eli Lilly Japan, Bristol Myers Squib, and Yakult Honsha outside the submitted work. Author MS received personal fees from Taiho, Chugai, Lilly, and Ono outside the submitted work. Author TS has received personal fees from Taiho. Author NB has received grant from Taiho, Ono and Bristol Myer-Squibb, and honorarium form Taiho, Ono, Chugai, Eli Lilly and Bristol Myer-Squibb. Author KN has received personal fees from Bayer, Chugai, Merck, and Eisai outside the submitted work. Author TY has received grants and personal fees from Taiho, Chugai, Yakult, personal fees from Ono, Bristol, Lilly, Terumo, Abbott, Johnson and Johnson, Covidien, Olympus, Nihon Kayaku, Daiichi Sankyo outside the submitted work. Author HK has received personal fees from Johnson & Johnson outside the submitted work.

Human rights statement

All procedures followed 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

Informed consent was obtained from all patients for inclusion in the study.


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Copyright information

© The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2019

Authors and Affiliations

  • Masanori Terashima
    • 1
    Email author
  • Yoshiaki Iwasaki
    • 2
  • Junki Mizusawa
    • 3
  • Hiroshi Katayama
    • 3
  • Kenichi Nakamura
    • 3
  • Hitoshi Katai
    • 4
  • Takaki Yoshikawa
    • 5
  • Yuichi Ito
    • 6
  • Masahide Kaji
    • 7
  • Yutaka Kimura
    • 8
  • Motohiro Hirao
    • 9
  • Makoto Yamada
    • 10
  • Akira Kurita
    • 11
  • Masakazu Takagi
    • 12
  • Narikazu Boku
    • 13
  • Takeshi Sano
    • 14
  • Mitsuru Sasako
    • 15
  • Stomach Cancer Study Group, Japan Clinical Oncology Group
  1. 1.Division of Gastric SurgeryShizuoka Cancer CenterNagaizumiJapan
  2. 2.Department of SurgeryTokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalTokyoJapan
  3. 3.JCOG Data Center/Operations OfficeNational Cancer Center HospitalTokyoJapan
  4. 4.Department of Gastric SurgeryNational Cancer Center HospitalTokyoJapan
  5. 5.Department of Gastrointestinal SurgeryKanagawa Cancer Center HospitalYokohamaJapan
  6. 6.Department of Gastroenterological SurgeryAichi Cancer Center HospitalNagoyaJapan
  7. 7.Department of SurgeryToyama Prefectural Central HospitalToyamaJapan
  8. 8.Department of SurgerySakai City HospitalSakaiJapan
  9. 9.Department of SurgeryNational Hospital Organization Osaka National HospitalOsakaJapan
  10. 10.Department of SurgeryGifu Municipal HospitalGifuJapan
  11. 11.Department of SurgeryNational Hospital Organization Shikoku Cancer CenterMatsuyamaJapan
  12. 12.Department of SurgeryShizuoka General HospitalShizuokaJapan
  13. 13.Department of Gastrointestinal OncologyNational Cancer Center HospitalTokyoJapan
  14. 14.Department of Gastroenterological SurgeryCancer Institute Hospital of Japanese Foundation for Cancer ResearchTokyoJapan
  15. 15.Department of SurgeryHyogo College of MedicineKobeJapan

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