Five-weekly S-1 plus cisplatin therapy combined with trastuzumab therapy in HER2-positive gastric cancer: a phase II trial and biomarker study (WJOG7212G)

Yuji Miura, Yasutaka Sukawa, Shuichi Hironaka, Misuzu Mori, Kazuhiro Nishikawa, Shinya Tokunaga, Hiroyuki Okuda, Takeshi Sakamoto, Keisei Taku, Kazuo Nishikawa, Toshikazu Moriwaki, Yuji Negoro, Yutaka Kimura, Keita Uchino, Katsunori Shinozaki, Hiroharu Shinozaki, Nobuyuki Musha, Hirotsugu Yoshiyama, Takashi Tsuda, Yoshinori MiyataNaotoshi Sugimoto, Tsuyoshi Shirakawa, Miki Ito, Kimio Yonesaka, Kenichi Yoshimura, Narikazu Boku, Katsuhiko Nosho, Toshimi Takano, Ichinosuke Hyodo

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)84-95
Number of pages12
JournalGastric Cancer
Issue number1
Publication statusPublished - 2018 Jan 1


  • First-line chemotherapy
  • Gastric adenocarcinoma
  • Neuregulin 1
  • S-1
  • Trastuzumab

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology
  • Cancer Research


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