Paclitaxel plus valproic acid versus paclitaxel alone as second or third line therapy for advanced gastric cancer: a randomized phase 2 trial

Date 29 June 2016
Event ESMO World Congress on Gastrointestinal Cancer 2016
Session ESMO World Congress on Gastrointestinal Cancer 2016 - Abstracts book
Presenter J. Kinoshita
Citation Annals of Oncology (2016) 27 (2): 1-85. 10.1093/annonc/mdw199
Authors J. Kinoshita1, S. Fushida1, M. Kaji2, K. Oyama1, Y. Hirono3, H. Nezuka4, T. Takeda5, T. Tsukada6, S. Ohyama7, T. Fujimura8, T. Ohta1
  • 1Kanazawa University Hospital, Kanazawa, Japan, /
  • 2Department of Surgery, Toyama Prefectural Central Hospital, Toyama, Japan, /
  • 3First Department of Surgery, Fukui University Hospital, Yoshida-gun, Japan, /
  • 4Department of Surgery, Yatsuo General Hospital, Toyama City, Japan, /
  • 5Department of Surgery, Ishikawa Matto Central Hospital, Hakusan City, Japan, /
  • 6Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan, /
  • 7Department of Surgery, Kanazawa Medical Center, Kanazawa, Japan, /
  • 8Department of Surgery, Toyama City Hospital, Toyama City, Japan, /

Abstract

Gastric cancer is the fifth most common malignancy, and the third leading cause of cancer mortality worldwide. The combination of fluoropyrimidine and platinum is standard first-line chemotherapy, and weekly paclitaxel (wPTX) has become the preferable second-line chemotherapy in Japan. Although numerous clinical studies have considered the efficacy of molecular targeted agents combined with conventional chemotherapy, efficacy in gastric cancer was demonstrated only by trastuzumab as a first-line and ramucirumab as a second-line treatment. Other candidates for molecular targeted therapy are needed. Histone deacetylase (HDAC) inhibitors have been shown to have anti-proliferative activity through cell cycle arrest, differentiation, and apoptosis in gastric cancer cells. One HDAC inhibitor, valproic acid (VPA), also inhibits tumor growth by inducing apoptosis and enhances the efficacy of paclitaxel in a mouse xenograft model of gastric cancer. wPTX plus VPA as a second-line chemotherapy is expected to improve survival in gastric cancer patients.