TY - JOUR
T1 - Randomized phase II study of second-line chemotherapy with the best available 5-fluorouracil regimen versus weekly administration of paclitaxel in far advanced gastric cancer with severe peritoneal metastases refractory to 5-fluorouracil-containing regimens (JCOG0407)
AU - Nishina, Tomohiro
AU - Boku, Narikazu
AU - Gotoh, Masahiro
AU - Shimada, Yasuhiro
AU - Hamamoto, Yasuo
AU - Yasui, Hirofumi
AU - Yamaguchi, Kensei
AU - Kawai, Hiroki
AU - Nakayama, Norisuke
AU - Amagai, Kenji
AU - Mizusawa, Junki
AU - Nakamura, Kenichi
AU - Shirao, Kuniaki
AU - Ohtsu, Atsushi
N1 - Funding Information:
The authors dedicate this manuscript to Dr Hiroya Takiuchi, who unfortunately passed away in 2012. Without his great effort as the study coordinator, this study would not have been completed. The authors also thank Naoko Murata and Yuka Sakamoto for data management, Haruhiko Fukuda as a chair of the Japan Clinical Oncology Group Data Center supporting this study, and the Data and Safety Monitoring Committee and the Audit Committee of the Japan Clinical Oncology Group. This study was supported by Grants-in-Aid for Cancer Research (14S-3, 14S-4, 17S-3, 17S-5, 20S-3, 20S-6, 26-A-4) and by Health and Labour Sciences Research Grants for Clinical Cancer Research (14-Gan-36, 17-Gan-008, 20-Gan-008) from the Ministry of Health, Labour and Welfare of Japan.
Funding Information:
T.N. has received research funding from Taiho Pharmaceutical Co. Ltd. N.B. has received honoraria from Taiho Pharmaceutical Co. Ltd. N.B. has also received research funding from Chugai Pharmaceutical Co. Ltd. Y.S. has received research funding from Taiho Pharmaceutical Co. K.Y. has received honoraria from Merck Serono Co. Ltd., Bristol-Myers Squibb, and Takeda Pharmaceutical Co. Ltd. K.Y. has received research funding from Merck Serono Co., Ltd., Bristol-Myers Squibb, and Takeda Pharmaceutical Co. Ltd. K.A. has received research funding from Taiho Pharmaceutical Co. Ltd. K.S. has received research funding from Taiho Pharmaceutical Co. Ltd. All other authors declare that they have no conflict of interest.
Publisher Copyright:
© 2015, The International Gastric Cancer Association and The Japanese Gastric Cancer Association.
PY - 2016/7/1
Y1 - 2016/7/1
N2 - Background: This randomized phase II study compared weekly administration of paclitaxel (wPTX) with the best available 5-fluorouracil (5-FU) regimen as second-line treatment for advanced gastric cancer patients with severe peritoneal metastasis refractory to fluoropyrimidine. Methods: In the best available 5-FU arm, continuous infusion of 5-FU (800 mg/m2/day, days 1–5, every 4 weeks) was given to patients with prior chemotherapy including bolus 5-FU, and methotrexate and 5-FU sequential bolus injection (methotrexate at 100 mg/m2 followed by bolus 5-FU at 600 mg/m2 with leucovorin, weekly) was given to those who had previously received continuous infusion of 5-FU or oral administration of fluoropyrimidine. In the wPTX arm, paclitaxel (80 mg/m2) was administered on days 1, 8, and 15, every 4 weeks. This study adopted a screening design (one-sided α = 30 %) with the primary end point of overall survival. Results: One hundred patients were randomized to the 5-FU arm (n = 49) or the wPTX arm (n = 51). Although the median survival time was 7.7 months in both arms, the 2-year survival rates were 2.9 % in the 5-FU arm and 9.1 % in the wPTX arm [hazard ratio 0.89 (95 % confidence interval 0.57–1.38), one-sided p = 0.298}. The median progression-free survival was longer with wPTX than with 5-FU [3.7 months vs 2.4 months; hazard ratio 0.58 (95 % confidence interval 0.38–0.88), one-sided p = 0.005]. The incidences of grade 4 neutropenia, grade 3/4 febrile neutropenia, diarrhea, and treatment-related death were 6 %, 4 %, 10 %, and 2 %, respectively, in the 5-FU arm and 2 %, 0 %, 0 %, and 0 %, respectively, in the wPTX arm. Conclusions: As second-line chemotherapy, wPTX appears feasible and promising. This regimen can be included in a test arm in future phase III trials for treatment of advanced gastric cancer with severe peritoneal metastasis.
AB - Background: This randomized phase II study compared weekly administration of paclitaxel (wPTX) with the best available 5-fluorouracil (5-FU) regimen as second-line treatment for advanced gastric cancer patients with severe peritoneal metastasis refractory to fluoropyrimidine. Methods: In the best available 5-FU arm, continuous infusion of 5-FU (800 mg/m2/day, days 1–5, every 4 weeks) was given to patients with prior chemotherapy including bolus 5-FU, and methotrexate and 5-FU sequential bolus injection (methotrexate at 100 mg/m2 followed by bolus 5-FU at 600 mg/m2 with leucovorin, weekly) was given to those who had previously received continuous infusion of 5-FU or oral administration of fluoropyrimidine. In the wPTX arm, paclitaxel (80 mg/m2) was administered on days 1, 8, and 15, every 4 weeks. This study adopted a screening design (one-sided α = 30 %) with the primary end point of overall survival. Results: One hundred patients were randomized to the 5-FU arm (n = 49) or the wPTX arm (n = 51). Although the median survival time was 7.7 months in both arms, the 2-year survival rates were 2.9 % in the 5-FU arm and 9.1 % in the wPTX arm [hazard ratio 0.89 (95 % confidence interval 0.57–1.38), one-sided p = 0.298}. The median progression-free survival was longer with wPTX than with 5-FU [3.7 months vs 2.4 months; hazard ratio 0.58 (95 % confidence interval 0.38–0.88), one-sided p = 0.005]. The incidences of grade 4 neutropenia, grade 3/4 febrile neutropenia, diarrhea, and treatment-related death were 6 %, 4 %, 10 %, and 2 %, respectively, in the 5-FU arm and 2 %, 0 %, 0 %, and 0 %, respectively, in the wPTX arm. Conclusions: As second-line chemotherapy, wPTX appears feasible and promising. This regimen can be included in a test arm in future phase III trials for treatment of advanced gastric cancer with severe peritoneal metastasis.
KW - 5-Fluorouracil
KW - Gastric cancer
KW - Paclitaxel
KW - Peritoneal metastasis
KW - Phase II study
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U2 - 10.1007/s10120-015-0542-8
DO - 10.1007/s10120-015-0542-8
M3 - Article
C2 - 26386560
AN - SCOPUS:84942067027
VL - 19
SP - 902
EP - 910
JO - Gastric Cancer
JF - Gastric Cancer
SN - 1436-3291
IS - 3
ER -