Paclitaxel plus valproic acid versus paclitaxel alone as second- or third-line therapy for advanced gastric cancer: a randomized Phase II trial
Sachio Fushida,1 Jun Kinoshita,1 Masahide Kaji,2 Katsunobu Oyama,1 Yasuo Hirono,3 Tomoya Tsukada,2 Takashi Fujimura,4 Tetsuo Ohta1 On behalf of the Digestive Disease Support Organization Study Group 1Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, 2Department of...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Dove Medical Press
2016-07-01
|
Series: | Drug Design, Development and Therapy |
Subjects: | |
Online Access: | https://www.dovepress.com/paclitaxel-plus-valproic-acid-versus-paclitaxel-alone-as-second--or-th-peer-reviewed-article-DDDT |
id |
doaj-7b8fd2abe664433a8cbc0e039be3bae3 |
---|---|
record_format |
Article |
spelling |
doaj-7b8fd2abe664433a8cbc0e039be3bae32020-11-25T00:26:27ZengDove Medical PressDrug Design, Development and Therapy1177-88812016-07-012016Issue 12353235828045Paclitaxel plus valproic acid versus paclitaxel alone as second- or third-line therapy for advanced gastric cancer: a randomized Phase II trialFushida SKinoshita JKaji MOyama KHirono YTsukada TFujimura TOhta TSachio Fushida,1 Jun Kinoshita,1 Masahide Kaji,2 Katsunobu Oyama,1 Yasuo Hirono,3 Tomoya Tsukada,2 Takashi Fujimura,4 Tetsuo Ohta1 On behalf of the Digestive Disease Support Organization Study Group 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, Toyama City Hospital, Toyama, Japan Background: Weekly paclitaxel (wPTX) is the preferred second-line chemotherapy for gastric cancer in Japan. Histone deacetylase inhibitors have been shown to decrease proliferation through cell-cycle arrest, differentiation, and apoptosis in gastric cancer cells. One histone deacetylase inhibitor, valproic acid (VPA), also inhibits tumor growth by inducing apoptosis and enhances the efficacy of paclitaxel (PTX), shown in a murine gastric cancer model. This Phase II trial was designed to evaluate the benefits of adding VPA to wPTX in patients with gastric cancer refractory to first-line treatment with fluoropyrimidine.Patients and methods: The patients were randomly assigned in a 1:1 ratio to receive PTX 80 mg/m2 intravenously on days 1, 8, and 15, every 4 weeks, or a dose of PTX plus VPA taken everyday at 7.5 mg/kg twice daily. Random assignment was carried out at the data center with a minimization method adjusted by the Eastern Cooperative Oncology Group performance status (0–1 vs 2), prior chemotherapy (first-line vs second-line), and measurable lesions (presence vs absence). The primary end point was the overall survival (OS) rate, and the secondary end points were the progression-free survival rate and safety analysis.Results: Sixty-six patients were randomly assigned to receive wPTX (n=33) or wPTX plus VPA (n=33). The median OS was 9.8 months in the wPTX group and 8.7 months in the wPTX plus VPA group (hazard ratio 1.19; 95% CI 0.702–2.026; P=0.51). The median progression-free survival was 4.5 months in the wPTX group and 3.0 months in the wPTX plus VPA group (hazard ratio 1.29; 95% CI 0.753–2.211; P=0.35). Grade 3–4 adverse events were neutropenia (3.1%), pneumonia (1.6%), liver injury (1.6%), brain infarction (1.6%), and rupture of aorta (1.6%).Conclusion: No statistically significant difference was observed between wPTX and wPTX plus VPA for OS. Keywords: valproic acid, paclitaxel, second- or third-line therapy, advanced gastric cancerhttps://www.dovepress.com/paclitaxel-plus-valproic-acid-versus-paclitaxel-alone-as-second--or-th-peer-reviewed-article-DDDTvalproic acidpaclitaxelsecond- or third-line therapyadvanced gastric cancer |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Fushida S Kinoshita J Kaji M Oyama K Hirono Y Tsukada T Fujimura T Ohta T |
spellingShingle |
Fushida S Kinoshita J Kaji M Oyama K Hirono Y Tsukada T Fujimura T Ohta T Paclitaxel plus valproic acid versus paclitaxel alone as second- or third-line therapy for advanced gastric cancer: a randomized Phase II trial Drug Design, Development and Therapy valproic acid paclitaxel second- or third-line therapy advanced gastric cancer |
author_facet |
Fushida S Kinoshita J Kaji M Oyama K Hirono Y Tsukada T Fujimura T Ohta T |
author_sort |
Fushida S |
title |
Paclitaxel plus valproic acid versus paclitaxel alone as second- or third-line therapy for advanced gastric cancer: a randomized Phase II trial |
title_short |
Paclitaxel plus valproic acid versus paclitaxel alone as second- or third-line therapy for advanced gastric cancer: a randomized Phase II trial |
title_full |
Paclitaxel plus valproic acid versus paclitaxel alone as second- or third-line therapy for advanced gastric cancer: a randomized Phase II trial |
title_fullStr |
Paclitaxel plus valproic acid versus paclitaxel alone as second- or third-line therapy for advanced gastric cancer: a randomized Phase II trial |
title_full_unstemmed |
Paclitaxel plus valproic acid versus paclitaxel alone as second- or third-line therapy for advanced gastric cancer: a randomized Phase II trial |
title_sort |
paclitaxel plus valproic acid versus paclitaxel alone as second- or third-line therapy for advanced gastric cancer: a randomized phase ii trial |
publisher |
Dove Medical Press |
series |
Drug Design, Development and Therapy |
issn |
1177-8881 |
publishDate |
2016-07-01 |
description |
Sachio Fushida,1 Jun Kinoshita,1 Masahide Kaji,2 Katsunobu Oyama,1 Yasuo Hirono,3 Tomoya Tsukada,2 Takashi Fujimura,4 Tetsuo Ohta1 On behalf of the Digestive Disease Support Organization Study Group 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, Toyama City Hospital, Toyama, Japan Background: Weekly paclitaxel (wPTX) is the preferred second-line chemotherapy for gastric cancer in Japan. Histone deacetylase inhibitors have been shown to decrease proliferation through cell-cycle arrest, differentiation, and apoptosis in gastric cancer cells. One histone deacetylase inhibitor, valproic acid (VPA), also inhibits tumor growth by inducing apoptosis and enhances the efficacy of paclitaxel (PTX), shown in a murine gastric cancer model. This Phase II trial was designed to evaluate the benefits of adding VPA to wPTX in patients with gastric cancer refractory to first-line treatment with fluoropyrimidine.Patients and methods: The patients were randomly assigned in a 1:1 ratio to receive PTX 80 mg/m2 intravenously on days 1, 8, and 15, every 4 weeks, or a dose of PTX plus VPA taken everyday at 7.5 mg/kg twice daily. Random assignment was carried out at the data center with a minimization method adjusted by the Eastern Cooperative Oncology Group performance status (0–1 vs 2), prior chemotherapy (first-line vs second-line), and measurable lesions (presence vs absence). The primary end point was the overall survival (OS) rate, and the secondary end points were the progression-free survival rate and safety analysis.Results: Sixty-six patients were randomly assigned to receive wPTX (n=33) or wPTX plus VPA (n=33). The median OS was 9.8 months in the wPTX group and 8.7 months in the wPTX plus VPA group (hazard ratio 1.19; 95% CI 0.702–2.026; P=0.51). The median progression-free survival was 4.5 months in the wPTX group and 3.0 months in the wPTX plus VPA group (hazard ratio 1.29; 95% CI 0.753–2.211; P=0.35). Grade 3–4 adverse events were neutropenia (3.1%), pneumonia (1.6%), liver injury (1.6%), brain infarction (1.6%), and rupture of aorta (1.6%).Conclusion: No statistically significant difference was observed between wPTX and wPTX plus VPA for OS. Keywords: valproic acid, paclitaxel, second- or third-line therapy, advanced gastric cancer |
topic |
valproic acid paclitaxel second- or third-line therapy advanced gastric cancer |
url |
https://www.dovepress.com/paclitaxel-plus-valproic-acid-versus-paclitaxel-alone-as-second--or-th-peer-reviewed-article-DDDT |
work_keys_str_mv |
AT fushidas paclitaxelplusvalproicacidversuspaclitaxelaloneassecondorthirdlinetherapyforadvancedgastriccancerarandomizedphaseiitrial AT kinoshitaj paclitaxelplusvalproicacidversuspaclitaxelaloneassecondorthirdlinetherapyforadvancedgastriccancerarandomizedphaseiitrial AT kajim paclitaxelplusvalproicacidversuspaclitaxelaloneassecondorthirdlinetherapyforadvancedgastriccancerarandomizedphaseiitrial AT oyamak paclitaxelplusvalproicacidversuspaclitaxelaloneassecondorthirdlinetherapyforadvancedgastriccancerarandomizedphaseiitrial AT hironoy paclitaxelplusvalproicacidversuspaclitaxelaloneassecondorthirdlinetherapyforadvancedgastriccancerarandomizedphaseiitrial AT tsukadat paclitaxelplusvalproicacidversuspaclitaxelaloneassecondorthirdlinetherapyforadvancedgastriccancerarandomizedphaseiitrial AT fujimurat paclitaxelplusvalproicacidversuspaclitaxelaloneassecondorthirdlinetherapyforadvancedgastriccancerarandomizedphaseiitrial AT ohtat paclitaxelplusvalproicacidversuspaclitaxelaloneassecondorthirdlinetherapyforadvancedgastriccancerarandomizedphaseiitrial |
_version_ |
1725344069140348928 |