title: Randomized Phase II trial of paclitaxel plus valproic acid vs paclitaxel alone as second-line therapy for patients with advanced gastric cancer.
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.
authors.affiliation: Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.
authors.forename: Sachio
authors.initials: S
authors.lastname: Fushida
authors.affiliation: Department of Surgery, Toyama Prefectural Central Hospital, Toyama, Japan.
authors.forename: Masahide
authors.initials: M
authors.lastname: Kaji
authors.affiliation: Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.
authors.forename: Katsunobu
authors.initials: K
authors.lastname: Oyama
authors.affiliation: First Department of Surgery, Fukui University Hospital, Fukui, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Hirono
authors.affiliation: Department of Surgery, Yatsuo General Hospital, Toyama, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nezuka
authors.affiliation: Department of Surgery, Ishikawa Matto Central Hospital, Hakusan, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Takeda
authors.affiliation: Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Tsukada
authors.affiliation: First Department of Surgery, Fukui University Hospital, Fukui, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Fujimoto
authors.affiliation: Department of Surgery, Kanazawa Medical Center, Kanazawa, Japan.
authors.forename: Shigekazu
authors.initials: S
authors.lastname: Ohyama
authors.affiliation: Toyama City Hospital, Toyama, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujimura
authors.affiliation: Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ohta
keywords: advanced gastric cancer; paclitaxel; second-line therapy; valproic acid