Long-term outcomes of preoperative docetaxel with cisplatin plus S-1 therapy for gastric cancer with extensive nodal metastasis (JCOG1002)
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Preoperative chemotherapy with cisplatin plus S-1 (CS) followed by gastrectomy with D2 plus para-aortic lymph node (PAN) dissection is regarded as a standard treatment in Japan for advanced gastric cancer with bulky lymph node (BN) and/or PAN metastasis. In the JCOG1002, we added docetaxel to CS (DCS) to further improve long-term outcomes. However, the primary endpoint, clinical response rate (RR), did not reach the expected level (Ito et al. in Gastric Cancer 20:322–31, 2017). Herein, we report our long-term survival results.
Patients with BN and/or PAN metastasis received 2 or 3 cycles of DCS therapy (docetaxel at 40 mg/m2 and cisplatin at 60 mg/m2 on day 1 and S-1 at 80 mg/m2 per day for 2 weeks, followed by a 2-week rest) followed by gastrectomy with D2 plus PAN dissection and postoperative S-1 for 1 year.
Between July 2011 and May 2013, 53 patients were enrolled. Clinically, 17.0% had both PAN and BN metastasis, and the rest had either PAN (26.4%) or BN (56.6%) metastasis. Among all eligible patients, the 5-year overall survival was 54.9% (95% confidence interval 40.3–67.3%) at the last follow-up in May 2018. Among 44 eligible patients with R0 resection, the 5-year relapse-free survival was 47.7% (95% confidence interval 32.5–61.5%).
Adding docetaxel to CS in preoperative chemotherapy for extensive nodal metastasis improved neither short-term outcomes nor long-term survival. Preoperative chemotherapy with CS followed by D2 + PAN dissection and postoperative S-1 remains the standard of care for patients with extensive nodal metastasis.
KeywordsGastric cancer Extensive lymph node metastasis Preoperative chemotherapy DCS
We thank all of the patients, their families, the investigators and medical staff members who participated in this study. The authors also thank M. Miyazawa (Japan Clinical Oncology Group Data Center) for assistance and support with data collection, and H. Fukuda (Japan Clinical Oncology Group Data Center) for oversight of the study.
This study was supported by the National Cancer Center Research and Development Fund (23-A-16, 23-A-19, 26-A-4, 29-A-3) and a Health and Labour Sciences Research Grant for Clinical Cancer Research (H22-Gan-016) from the Ministry of Health, Labour and Welfare, Japan.
Compliance with ethical standards
Conflicts of interest
Daisuke Takahari reports grants and personal fees from Taiho Pharmaceutical Co. and Ono Pharmaceutical Co., and personal fees from Eli Lilly Japan, Bristol-Myers Squibb, Yakult Honsha Co., Ltd., Chugai Pharmaceutical Co., Ltd., outside the submitted work. Seiji Ito reports grants from National Cancer Center, Japan, Ministry of Health, Labour and Welfare, Japan, during the conduct of the study, grants and personal fees from Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., personal fees from Taiho Pharmaceutical Co., grants from Merck Sharp and Dohme, outside the submitted work. Junki Mizusawa reports grants from Ministry of Health, Labour and Welfare, Japan, Japan Agency for Medical Research and Development (AMED), during the conduct of the study. Hiroshi Katayama reports grants from Ministry of Health, Labour and Welfare, Japan, AMED, during the conduct of the study; personal fees from Johnson & Johnson, outside the submitted work. Masanori Terashima reports personal fees from Taiho Pharmaceutical Co., Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Bristol-Myers Squibb, Yakult Honsha Co., Ltd., Takeda Pharmaceutical Company Ltd., Eli Lilly Japan, Daiichi Sankyo, outside the submitted work. Mitsuru Sasako reports grants from Japanese Government, personal fees from Taiho Pharmaceutical Co, Sanofi Aventis, during the conduct of the study; grants from Japanese Goverment, personal fees from Chugai Pharmaceutical Co., Taiho Pharmaceutical Co., Yakult Honsha Co., Ltd., Sanofi Aventis, Eli Lilly Japan, Merck Sharp and Dohme Japan, outside the submitted work. Takeshi Sano received personal fees from Taiho Pharmaceutical Co. during the conduct of the study and has received personal fees from Chugai Pharmaceutical Co, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo, Ono Pharmaceutical Co., Eli Lilly Japan, Ethicon, Covidien, Olympus, outside of the submitted work. Shinji Morita, Takashi Nomura, Makoto Yamada, Yoshiyuki Fujiwara, Yutaka Kimura, Atsuki Ikeda, and Yoshio Kadokawa have no conflicts of interest to disclose.
Human rights statement and informed consent
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. Informed consent or an appropriate substitute for it was obtained from all patients for their inclusion in this study.
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