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Randomized Phase II trial of paclitaxel plus valproic acid vs paclitaxel alone as second-line therapy for patients with advanced gastric cancer

Authors Fushida S, Kaji M, Oyama K, Hirono Y, Nezuka H, Takeda T, Tsukada T, Fujimoto D, Ohyama S, Fujimura T, Ohta T

Received 18 February 2015

Accepted for publication 23 March 2015

Published 23 April 2015 Volume 2015:8 Pages 939—941


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Professor Daniele Santini

Sachio Fushida,1 Masahide Kaji,2 Katsunobu Oyama,1 Yasuo Hirono,3 Hideaki Nezuka,4 Toshiya Takeda,5 Tomoya Tsukada,1 Daisuke Fujimoto,3 Shigekazu Ohyama,6 Takashi Fujimura,7 Tetsuo Ohta1

On behalf of the Digestive Disease Support Organization (DDSO)

1Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, 2Department of Surgery, Toyama Prefectural Central Hospital, Toyama, 3First Department of Surgery, Fukui University Hospital, Fukui, 4Department of Surgery, Yatsuo General Hospital, Toyama, 5Department of Surgery, Ishikawa Matto Central Hospital, Hakusan, 6Department of Surgery, Kanazawa Medical Center, Kanazawa, 7Toyama City Hospital, Toyama, Japan

Abstract: The standard regimen of second-line chemotherapy for patients with unresectable gastric cancer has not been established. However, weekly paclitaxel (wPTX) has become the preferable second-line chemotherapy in Japan. Histone deacetylase (HDAC) inhibitors have been shown to have antiproliferative 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. A multicenter randomized Phase II study was conducted to compare the effects of wPTX plus VPA and wPTX alone. A total of 66 patients participated in this study. The primary end point of the study was overall survival, and secondary end points were progression-free survival, response rate, and assessment of peripheral neuropathy.

Keywords: valproic acid, paclitaxel, second-line therapy, advanced gastric cancer

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