Yuji Miura1, Yasutaka Sukawa2, Shuichi Hironaka3, Misuzu Mori4, Kazuhiro Nishikawa5, Shinya Tokunaga6, Hiroyuki Okuda7, Takeshi Sakamoto8, Keisei Taku9, Kazuo Nishikawa10, Toshikazu Moriwaki11, Yuji Negoro12, Yutaka Kimura13, Keita Uchino14, Katsunori Shinozaki15, Hiroharu Shinozaki16, Nobuyuki Musha17, Hirotsugu Yoshiyama18, Takashi Tsuda19, Yoshinori Miyata20, Naotoshi Sugimoto21, Tsuyoshi Shirakawa22, Miki Ito23, Kimio Yonesaka24, Kenichi Yoshimura25, Narikazu Boku26, Katsuhiko Nosho27, Toshimi Takano1, Ichinosuke Hyodo11. 1. Department of Medical Oncology, Toranomon Hospital, 2-2-2 Toranomon Minato-ku, Tokyo, 105-8470, Japan. 2. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo, 160-8582, Japan. sukawa@keio.jp. 3. Clinical Trial Promotion Department, Chiba Cancer Center, 666-2 Nitona-Cho Chuo-ku, Chiba, 260-8717, Japan. 4. Department of Clinical Oncology, Jichi Medical University Hospital, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan. 5. Department of Surgery, Osaka General Medical Center, 3-1-56 Bandaihigashi Sumiyoshi-ku, Osaka, 558-0056, Japan. 6. Department of Medical Oncology, Osaka City General Hospital, 2-13-22 Miyakojima-hondori Miyakojima-ku, Osaka, 534-0021, Japan. 7. Department of Medical Oncology, Keiyukai Sapporo Hospital, Kita 1-1 Hon-dori 14 chome, Shiroishi-ku, Sapporo, Hokkaido, 003-0027, Japan. 8. Department of Gastroenterological Oncology, Hyogo Cancer Center, 13-70 Kitaoji-cho, Akashi, Hyogo, 673-0021, Japan. 9. Department of Medical Oncology, Shizuoka General Hospital, 4-27-1 Kita Ando Aoi-ku, Shizuoka, 420-8527, Japan. 10. Department of Medical Oncology and Hematology, Oita University Faculty of Medicine, 1-1 Hasamamachi Idaigaoka, Yufu, Oita, 879-5503, Japan. 11. Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai Tsukuba, Ibaraki, 305-8575, Japan. 12. Department of Gastroenterology, Kochi Health Sciences Center, 2125-1 Ike, Kochi, 781-8555, Japan. 13. Department of Surgery, Sakai City Medical Center, 1-1-1 Ebaraji-cho Nishi-ku, Sakai, Osaka, 593-8304, Japan. 14. Department of Medical Oncology, Kyushu Medical Center, 1-8-1 Jigyohama Chuo-ku, Fukuoka, 810-8563, Japan. 15. Division of Clinical Oncology, Hiroshima Prefectural Hospital, 1-5-54 Ujinakanda Minami-ku, Hiroshima, 734-0004, Japan. 16. Department of Surgery, Saiseikai Utsunomiya Hospital, 911-1 Takebayashimachi Utsunomiya, Tochigi, 321-0974, Japan. 17. Department of Surgery, Saiseikai Niigata Daini Hospital, 280-7 Teraji Nishi-ku, Niigata, 950-1104, Japan. 18. Department of Gastroenterological Surgery, Ehime Prefectural Central Hospital, 83 Kasugamachi, Matsuyama, Ehime, 790-0024, Japan. 19. Department of Clinical Oncology, School of Medicine, St Marianna University, 2-16-1 Sugao Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan. 20. Department of Medical Oncology, Saku Central Hospital Advanced Care Center, 3400-28 Nakagomi, Saku, Nagano, 385-0051, Japan. 21. Department of Clinical Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3 Nakamichi Higashinari-ku, Osaka, 537-8511, Japan. 22. Department of Oncology, Miyazaki Prefectural Miyazaki Hospital, 5-30 Kitatakamatsucho, Miyazaki, 880-8510, Japan. 23. Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, S1 W17, Chuo-ku, Hokkaido, 060-8556, Japan. 24. Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 Ohno-higashi Osaka-sayama, Osaka, 589-8511, Japan. 25. Innovative Clinical Research Center, Kanazawa University Hospital, 13-1 Takaramachi, Kanazawa, Ishikawa, 920-0934, Japan. 26. Division of Gastrointestinal Medical Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji Chuo-ku, Tokyo, 104-0045, Japan. 27. Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, S1 W16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan.
Abstract
BACKGROUND: Five-weekly S-1 plus cisplatin (SP) therapy is the standard care for advanced gastric or esophagogastric junction cancer (GC/EGJC) in East Asia. However, its efficacy and safety when combined with trastuzumab therapy for human epidermal growth factor receptor 2 (HER2)-positive advanced GC/EGJC remains unclear. METHODS: Patients received 5-weekly SP therapy (S-1 at 40-60 mg twice daily for 21 days plus cisplatin at 60 mg/m2 on day 8, every 5 weeks) plus trastuzumab therapy (first dose of 8 mg/kg, then 6 mg/kg every 3 weeks). The primary end point was the response rate, and the secondary end points included progression-free survival, overall survival, safety, and serum biomarker levels. RESULTS: Forty-four patients were enrolled. The response rate, progression-free survival, and overall survival were 61% (95% confidence interval 46-76%), 5.9 months, and 16.5 months respectively. The commonest grade 3 or grade 4 adverse events were neutropenia (30%) and anorexia (25%). A significantly higher response rate (92% vs 43%; P = 0.008) and longer progression-free survival (median 14.5 months vs 4.2 months; P = 0.028) were observed in patients with high (n = 14) compared with low (n = 17) pretreatment serum neuregulin 1 levels. CONCLUSIONS: Five-weekly SP therapy combined with trastuzumab therapy showed a good antitumor response and acceptable toxicity in HER2-positive advanced GC/EGJC. Serum neuregulin 1 might be associated with the efficacy of this treatment regimen.
BACKGROUND: Five-weekly S-1 plus cisplatin (SP) therapy is the standard care for advanced gastric or esophagogastric junction cancer (GC/EGJC) in East Asia. However, its efficacy and safety when combined with trastuzumab therapy for human epidermal growth factor receptor 2 (HER2)-positive advanced GC/EGJC remains unclear. METHODS:Patients received 5-weekly SP therapy (S-1 at 40-60 mg twice daily for 21 days plus cisplatin at 60 mg/m2 on day 8, every 5 weeks) plus trastuzumab therapy (first dose of 8 mg/kg, then 6 mg/kg every 3 weeks). The primary end point was the response rate, and the secondary end points included progression-free survival, overall survival, safety, and serum biomarker levels. RESULTS: Forty-four patients were enrolled. The response rate, progression-free survival, and overall survival were 61% (95% confidence interval 46-76%), 5.9 months, and 16.5 months respectively. The commonest grade 3 or grade 4 adverse events were neutropenia (30%) and anorexia (25%). A significantly higher response rate (92% vs 43%; P = 0.008) and longer progression-free survival (median 14.5 months vs 4.2 months; P = 0.028) were observed in patients with high (n = 14) compared with low (n = 17) pretreatment serum neuregulin 1 levels. CONCLUSIONS: Five-weekly SP therapy combined with trastuzumab therapy showed a good antitumor response and acceptable toxicity in HER2-positive advanced GC/EGJC. Serum neuregulin 1 might be associated with the efficacy of this treatment regimen.
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