TY - JOUR
T1 - Multicenter retrospective analysis of systemic chemotherapy for unresectable combined hepatocellular and cholangiocarcinoma
AU - Kobayashi, Satoshi
AU - Terashima, Takeshi
AU - Shiba, Satoshi
AU - Yoshida, Yukio
AU - Yamada, Ikuhiro
AU - Iwadou, Shouta
AU - Horiguchi, Shigeru
AU - Takahashi, Hideaki
AU - Suzuki, Eiichiro
AU - Moriguchi, Michihisa
AU - Tsuji, Kunihiro
AU - Otsuka, Taiga
AU - Asagi, Akinori
AU - Kojima, Yasushi
AU - Takada, Ryoji
AU - Morizane, Chigusa
AU - Mizuno, Nobumasa
AU - Ikeda, Masafumi
AU - Ueno, Makoto
AU - Furuse, Junji
N1 - Funding Information:
Hakko Kirin, NanoCarrier, Ono Pharmaceutical and Takeda Pharmaceutical. J.F. is a consultant/advisor to and has received honoraria and research funding from Astellas Pharma, Bayer AG, Chugai Pharmaceutical, Eisai, Eli Lilly Japan K.K., Merck Sharp & Dohme, Novartis, Ono Pharmaceutical, Shionogi & Taiho Pharmaceutical and Yakult Honsha. J.F. is a consultant/advisor to AstraZeneca, Boehringer Ingelheim GmbH, Bristol‐Myers Squibb, Fujifilm, J‐Pharma, Kyowa Hakko Kirin, Otsuka Pharmaceutical, Sandoz, Sanofi and Zeria Pharmaceutical; is part of the Speaker's Bureau for Taiho Pharmaceutical and Yakult Honsha; and has received honoraria and research funding from Daiichi Sankyo, Merck Serono, Mochida Pharmaceutical, Sumitomo Dainippon Pharma and Takeda Pharmaceutical. J.F. has also received honoraria from AstraZeneca, EA Pharma, Mitsubishi Tanabe Pharma, Pfizer and Sawai Pharmaceutical and research funding from Bristol‐Myers Squibb, Janssen Pharmaceuticals, J‐Pharma, Kyowa Hakko Kirin, NanoCarrier, OncoTherapy Science and Zeria Pharmaceutical.
Funding Information:
This study was supported by a National Cancer Center Research and Development Fund (26‐A‐5) from the Ministry of Health, Labour, and Welfare of Japan. M.M. has received research funding from Kyowa Hakko Kirin and Merck Sharp & Dohme. Y.K has received research funding from Kyowa
Funding Information:
Funding information This study was supported by a National Cancer Center Research and Development Fund (26-A-5) from the Ministry of Health, Labour, and Welfare of Japan. M.M. has received research funding from Kyowa Hakko Kirin and Merck Sharp & Dohme. Y.K has received research funding from Kyowa Hakko Kirin, NanoCarrier, Ono Pharmaceutical and Takeda Pharmaceutical. J.F. is a consultant/advisor to and has received honoraria and research funding from Astellas Pharma, Bayer AG, Chugai Pharmaceutical, Eisai, Eli Lilly Japan K.K., Merck Sharp & Dohme, Novartis, Ono Pharmaceutical, Shionogi & Taiho Pharmaceutical and Yakult Honsha. J.F. is a consultant/advisor to AstraZeneca, Boehringer Ingelheim GmbH, Bristol-Myers Squibb, Fujifilm, J-Pharma, Kyowa Hakko Kirin, Otsuka Pharmaceutical, Sandoz, Sanofi and Zeria Pharmaceutical; is part of the Speaker's Bureau for Taiho Pharmaceutical and Yakult Honsha; and has received honoraria and research funding from Daiichi Sankyo, Merck Serono, Mochida Pharmaceutical, Sumitomo Dainippon Pharma and Takeda Pharmaceutical. J.F. has also received honoraria from AstraZeneca, EA Pharma, Mitsubishi Tanabe Pharma, Pfizer and Sawai Pharmaceutical and research funding from Bristol-Myers Squibb, Janssen Pharmaceuticals, J-Pharma, Kyowa Hakko Kirin, NanoCarrier, OncoTherapy Science and Zeria Pharmaceutical. We would especially like to thank Takuji Okusaka of the National Cancer Center Hospital (Tokyo, Japan) for organizing the research group.
Publisher Copyright:
© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
PY - 2018/8
Y1 - 2018/8
N2 - We conducted a multicenter retrospective analysis to evaluate the efficacy of systemic chemotherapy for unresectable combined hepatocellular and cholangiocarcinoma. We enrolled 36 patients with pathologically proven, unresectable combined hepatocellular and cholangiocarcinoma treated with systemic chemotherapy. The log-rank test determined the significance of each prognostic factor. Elevated alpha-fetoprotein, carcinoembryonic antigen and carbohydrate antigen 19-9 levels were observed in 58.3%, 16.7% and 38.9% of patients, respectively. First-line chemotherapy included platinum-containing regimens consisting of gemcitabine/cisplatin (n = 12) and fluorouracil/cisplatin (n = 11), sorafenib (n = 5) and others (n = 8). The median overall and progression-free survival times were 8.9 and 2.8 months, respectively, with an overall response rate of 5.6%. Prognostic factors associated with negative outcomes included poor performance status, no prior primary tumor resection, a Child-Pugh class of B, and elevated carcinoembryonic antigen levels with a hazard ratio of 2.25, 2.48, 3.25 and 2.84 by univariate analysis, respectively. The median overall survival times of the gemcitabine/cisplatin, fluorouracil/cisplatin, sorafenib and other groups were 11.9, 10.2, 3.5 and 8.1 months, respectively. Multivariate analysis revealed that the overall survival of patients within the sorafenib monotherapy group was poor compared with platinum-containing regimens (HR: 15.83 [95% CI: 2.25-111.43], P =.006). All 7 patients in the sorafenib group had progressive disease, including 2 patients with second-line therapy. In conclusion, the platinum-containing regimens such as gemcitabine/cisplatin were associated with more favorable outcomes than sorafenib monotherapy for unresectable combined hepatocellular and cholangiocarcinoma.
AB - We conducted a multicenter retrospective analysis to evaluate the efficacy of systemic chemotherapy for unresectable combined hepatocellular and cholangiocarcinoma. We enrolled 36 patients with pathologically proven, unresectable combined hepatocellular and cholangiocarcinoma treated with systemic chemotherapy. The log-rank test determined the significance of each prognostic factor. Elevated alpha-fetoprotein, carcinoembryonic antigen and carbohydrate antigen 19-9 levels were observed in 58.3%, 16.7% and 38.9% of patients, respectively. First-line chemotherapy included platinum-containing regimens consisting of gemcitabine/cisplatin (n = 12) and fluorouracil/cisplatin (n = 11), sorafenib (n = 5) and others (n = 8). The median overall and progression-free survival times were 8.9 and 2.8 months, respectively, with an overall response rate of 5.6%. Prognostic factors associated with negative outcomes included poor performance status, no prior primary tumor resection, a Child-Pugh class of B, and elevated carcinoembryonic antigen levels with a hazard ratio of 2.25, 2.48, 3.25 and 2.84 by univariate analysis, respectively. The median overall survival times of the gemcitabine/cisplatin, fluorouracil/cisplatin, sorafenib and other groups were 11.9, 10.2, 3.5 and 8.1 months, respectively. Multivariate analysis revealed that the overall survival of patients within the sorafenib monotherapy group was poor compared with platinum-containing regimens (HR: 15.83 [95% CI: 2.25-111.43], P =.006). All 7 patients in the sorafenib group had progressive disease, including 2 patients with second-line therapy. In conclusion, the platinum-containing regimens such as gemcitabine/cisplatin were associated with more favorable outcomes than sorafenib monotherapy for unresectable combined hepatocellular and cholangiocarcinoma.
KW - Cisplatin
KW - drug therapy
KW - gemcitabine
KW - prognosis
KW - sorafenib
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U2 - 10.1111/cas.13656
DO - 10.1111/cas.13656
M3 - Article
C2 - 29856900
AN - SCOPUS:85052502984
VL - 109
SP - 2549
EP - 2557
JO - Cancer Science
JF - Cancer Science
SN - 1347-9032
IS - 8
ER -