Randomised, multicentre prospective trial of transarterial chemoembolisation (TACE) plus sorafenib as compared with TACE alone in patients with hepatocellular carcinoma: TACTICS trial

被引：636

作者：

Kudo, Masatoshi ^{[1
]}

Ueshima, Kazuomi ^{[1
]}

Ikeda, Masafumi ^{[2
]}

Torimura, Takuji ^{[3
]}

Tanabe, Nobukazu ^{[4
]}

Aikata, Hiroshi ^{[5
]}

Izumi, Namiki ^{[6
]}

Yamasaki, Takahiro ^{[7
]}

Nojiri, Shunsuke ^{[8
]}

Hino, Keisuke ^{[9
]}

Tsumura, Hidetaka ^{[10
]}

Kuzuya, Teiji ^{[11
]}

Isoda, Norio ^{[12
]}

Yasui, Kohichiroh ^{[13
]}

Aino, Hajime ^{[14
]}

Ido, Akio ^{[15
]}

Kawabe, Naoto ^{[16
]}

Nakao, Kazuhiko ^{[17
]}

Wada, Yoshiyuki ^{[18
]}

Yokosuka, Osamu ^{[19
]}

Yoshimura, Kenichi ^{[20
]}

Okusaka, Takuji ^{[21
]}

Furuse, Junji ^{[22
]}

Kokudo, Norihiro ^{[23
]}

Okita, Kiwamu ^{[24
]}

Johnson, Philip James ^{[25
]}

Arai, Yasuaki ^{[26
]}

机构：

[1] Kindai Univ, Fac Med, Dept Gastroenterol & Hepatol, Osaka, Japan

[2] Natl Canc Ctr Hosp East, Dept Hepatobiliary & Pancreat Oncol, Kashiwa, Chiba, Japan

[3] Kurume Univ, Sch Med, Dept Gastroenterol & Hepatol, Kurume, Fukuoka, Japan

[4] Natl Hosp Org Sendai Med Ctr, Dept Gastroenterol, Sendai, Miyagi, Japan

[5] Hiroshima Univ, Dept Gastroenterol & Metab, Hiroshima, Japan

[6] Musashino Red Cross Hosp, Dept Gastroenterol, Tokyo, Japan

[7] Yamaguchi Univ, Dept Gastroenterol & Hepatol, Grad Sch Med, Ube, Yamaguchi, Japan

[8] Nagoya City Univ, Dept Gastroenterol & Metab, Grad Sch Med Sci, Nagoya, Aichi, Japan

[9] Kawasaki Med Sch, Dept Hepatol & Pancreatol, Kurashiki, Okayama, Japan

[10] Hyogo Canc Ctr, Dept Gastroenterol & Hepatol, Akashi, Hyogo, Japan

[11] Nagoya Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Nagoya, Nagoya, Aichi, Japan

[12] Jichi Med Univ, Div Gastroenterol, Dept Med, Shimotsuke, Tochigi, Japan

[13] Kyoto Prefectural Univ Med, Dept Gastroenterol & Hepatol, Kyoto, Japan

[14] Social Insurance Tagawa Hosp, Dept Med, Div Gastroenterol, Tagawa, Japan

[15] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Gastroenterol & Hepatol, Kagoshima, Japan

[16] Fujita Hlth Univ, Sch Med, Dept Liver Biliary Tract & Pancreas Dis, Toyoake, Aichi, Japan

[17] Nagasaki Univ, Grad Sch Biomed Sci, Dept Gastroenterol & Hepatol, Nagasaki, Japan

[18] Natl Hosp Org Kyushu Med Ctr, Clin Res Inst, Dept Hepatobiliary Pancreat Surg, Fukuoka, Japan

[19] Chiba Univ, Sch Med, Dept Gastroenterol, Chiba, Japan

[20] Hiroshima Univ, Ctr Integrated Med Res, Hiroshima, Japan

[21] Natl Canc Ctr, Dept Hepatobiliary & Pancreat Oncol, Tokyo, Japan

[22] Kyorin Univ, Fac Med, Dept Med Oncol, Mitaka, Tokyo, Japan

[23] Natl Ctr Global Hlth & Med, Dept Surg, Tokyo, Japan

[24] Shunan Mem Hosp, Dept Med, Kudamatsu, Yamaguchi, Japan

[25] Univ Liverpool, Dept Mol & Clin Canc Med, Liverpool, Merseyside, England

[26] Natl Canc Ctr, Dept Diagnost Radiol, Tokyo, Japan

来源：

GUT | 2020年 / 69卷 / 08期

关键词：

TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION; CLINICAL-PRACTICE GUIDELINES; ENDOTHELIAL GROWTH-FACTOR; PHASE-III; DOUBLE-BLIND; COMBINATION; THERAPY; EXPRESSION; MANAGEMENT; CANCER;

D O I：

10.1136/gutjnl-2019-318934

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Objective This trial compared the efficacy and safety of transarterial chemoembolisation (TACE) plus sorafenib with TACE alone using a newly established TACE -specific endpoint and pre-treatment of sorafenib before initial TACE. Design Patients with unresectable hepatocellular carcinoma (HCC) were randomised to TACE plus sorafenib (n=80) or TACE alone (n=76). Patients in the combination group received sorafenib 400 mg once daily for 2-3 weeks before TACE, followed by 800 mg once daily during on-demand conventional TACE sessions until time to untreatable (unTACE able) progression (TTUP), defined as untreatable tumour progression, transient deterioration to Child-Pugh C or appearance of vascular invasion/extrahepatic spread. Co-primary endpoints were progression-free survival (PFS), which is not a conventional one but defined as TTUP, or time to any cause of death plus overall survival (OS). Multiplicity was adjusted by gatekeeping hierarchical testing. Results Median PFS was significantly longer in the TACE plus sorafenib than in the TACE alone group (25.2 vs 13.5 months; p=0.006). OS was not analysed because only 73.6% of OS events were reached. Median TTUP (26.7 vs 20.6 months; p=0.02) was also significantly longer in the TACE plus sorafenib group. OS at 1 year and 2 years in TACE plus sorafenib group and TACE alone group were 96.2% and 82.7% and 77.2% and 64.6%, respectively. There were no unexpected toxicities. Conclusion TACE plus sorafenib significantly improved PFS over TACE alone in patients with unresectable HCC. Adverse events were consistent with those of previous TACE combination trials.

引用

页码：1492 / 1501

页数：10

共 33 条

[1] Clinical Decision Making and Research in Hepatocellular Carcinoma: Pivotal Role of Imaging Techniques [J].

Bruix, Jordi ;

Reig, Maria ;

Rimola, Jordi ;

Forner, Alejandro ;

Burrel, Marta ;

Vilana, Ramon ;

Ayuso, Carmen .

HEPATOLOGY, 2011, 54 (06) :2238-2244

[2] Management of Hepatocellular Carcinoma: An Update [J].

Bruix, Jordi ;

Sherman, Morris .

HEPATOLOGY, 2011, 53 (03) :1020-1022

[3] The combination of sorafenib with transarterial chemoembolisation for hepatocellular carcinoma [J].

Cabrera, R. ;

Pannu, D. S. ;

Caridi, J. ;

Firpi, R. J. ;

Soldevila-Pico, C. ;

Morelli, G. ;

Clark, V. ;

Suman, A. ;

George, T. J., Jr. ;

Nelson, D. R. .

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2011, 34 (02) :205-213

[4] Angiogenesis in cancer and other diseases [J].

Carmeliet, P ;

Jain, RK .

NATURE, 2000, 407 (6801) :249-257

[5] Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial [J].

Cheng, Ann-Lii ;

Kang, Yoon-Koo ;

Chen, Zhendong ;

Tsao, Chao-Jung ;

Qin, Shukui ;

Kim, Jun Suk ;

Luo, Rongcheng ;

Feng, Jifeng ;

Ye, Shenglong ;

Yang, Tsai-Sheng ;

Xu, Jianming ;

Sun, Yan ;

Liang, Houjie ;

Liu, Jiwei ;

Wang, Jiejun ;

Tak, Won Young ;

Pan, Hongming ;

Burock, Karin ;

Zou, Jessie ;

Voliotis, Dimitris ;

Guan, Zhongzhen .

LANCET ONCOLOGY, 2009, 10 (01) :25-34

[6] Gatekeeping strategies for clinical trials that do not require all primary effects to be significant [J].

Dmitrienko, A ;

Offen, WW ;

Westfall, PH .

STATISTICS IN MEDICINE, 2003, 22 (15) :2387-2400

[7]

European Assoc Study Liver, 2018, J HEPATOL, V69, P182, DOI 10.1016/j.jhep.2018.03.019

[8] Hepatocellular carcinoma [J].

Forner, Alejandro ;

Reig, Maria ;

Bruix, Jordi .

LANCET, 2018, 391 (10127) :1301-1314

[9] AASLD guidelines for the treatment of hepatocellular carcinoma [J].

Heimbach, Julie K. ;

Kulik, Laura M. ;

Finn, Richard S. ;

Sirlin, Claude B. ;

Abecassis, Michael M. ;

Roberts, Lewis R. ;

Zhu, Andrew X. ;

Murad, M. Hassan ;

Marrero, Jorge A. .

HEPATOLOGY, 2018, 67 (01) :358-380

[10] Hepatic Function during Repeated TACE Procedures and Prognosis after Introducing Sorafenib in Patients with Unresectable Hepatocellular Carcinoma: Multicenter Analysis [J].

Hiraoka, Atsushi ;

Kumada, Takashi ;

Kudo, Masatoshi ;

Hirooka, Masashi ;

Koizumi, Yohei ;

Hiasa, Yoichi ;

Tajiri, Kazuto ;

Toyoda, Hidenori ;

Tada, Toshifumi ;

Ochi, Hironori ;

Joko, Koji ;

Shimada, Noritomo ;

Deguchi, Akihiro ;

Ishikawa, Toru ;

Imai, Michitaka ;

Tsuji, Kunihiko ;

Michitaka, Kojiro .

DIGESTIVE DISEASES, 2017, 35 (06) :602-610

← 1 2 3 4 →