Sorafenib plus low-dose cisplatin and fluorouracil hepatic arterial infusion chemotherapy versus sorafenib alone in patients with advanced hepatocellular carcinoma (SILIUS): a randomised, open label, phase 3 trial

被引：272

作者：

Kudo, Masatoshi ^{[1
]}

Ueshima, Kazuomi ^{[1
]}

Yokosuka, Osamu ^{[2
]}

Ogasawara, Sadahisa ^{[2
]}

Obi, Shuntaro ^{[3
]}

Izumi, Namiki ^{[4
]}

Aikata, Hiroshi ^{[5
]}

Nagano, Hiroaki ^{[6
]}

Hatano, Etsuro ^{[7
]}

Sasaki, Yutaka ^{[8
]}

Hino, Keisuke ^{[9
]}

Kumada, Takashi ^{[10
]}

Yamamoto, Kazuhide ^{[11
]}

Imai, Yasuharu ^{[12
]}

Iwadou, Shouta ^{[13
]}

Ogawa, Chikara ^{[14
]}

Okusaka, Takuji ^{[15
]}

Kanai, Fumihiko ^{[2
]}

Akazawa, Kohei ^{[16
]}

Yoshimura, Ken-ichi ^{[17
]}

Johnson, Philip ^{[18
]}

Arai, Yasuaki ^{[15
]}

机构：

[1] Kindai Univ, Fac Med, Osaka, Japan

[2] Chiba Univ, Grad Sch Med, Chiba, Japan

[3] Kyoundo Hosp, Tokyo, Japan

[4] Japanese Red Cross Musashino Hosp, Musashino, Tokyo, Japan

[5] Hiroshima Univ Hosp, Hiroshima, Japan

[6] Osaka Univ, Grad Sch Med, Osaka, Japan

[7] Kyoto Univ, Grad Sch Med, Kyoto, Japan

[8] Kumamoto Univ, Grad Sch Med Sci, Kumamoto, Japan

[9] Kawasaki Med Sch, Kurashiki, Okayama, Japan

[10] Ogaki Municipal Hosp, Ogaki, Japan

[11] Okayama Univ, Sch Med, Okayama, Japan

[12] Ikeda Municipal Hosp, Ikeda, Osaka, Japan

[13] Hiroshima City Hosp, Hiroshima, Japan

[14] Takamatsu Red Cross Hosp, Takamatsu, Kagawa, Japan

[15] Natl Canc Ctr, Tokyo, Japan

[16] Niigata Univ, Niigata, Japan

[17] Kanazawa Univ, Kanazawa, Ishikawa, Japan

[18] Univ Liverpool, Liverpool, Merseyside, England

来源：

LANCET GASTROENTEROLOGY & HEPATOLOGY | 2018年 / 3卷 / 06期

关键词：

FINE-POWDER FORMULATION; 5-FLUOROURACIL; THERAPY;

D O I：

10.1016/S2468-1253(18)30078-5

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Background Hepatic arterial infusion chemotherapy plus sorafenib in phase 2 trials has shown favourable tumour control and a manageable safety profile in patients with advanced, unresectable hepatocellular carcinoma. However, no randomised phase 3 trial has tested the combination of sorafenib with continuous arterial infusion chemotherapy. We aimed to compare continuous hepatic arterial infusion chemotherapy plus sorafenib with sorafenib alone in patients with advanced, unresectable hepatocellular carcinoma. Methods We did an open-label, randomised, phase 3 trial (SILIUS) at 31 sites in Japan. Eligible patients were aged 20 years or older, with advanced hepatocellular carcinoma not suitable for resection, local ablation, or transarterial chemoembolisation; Eastern Cooperative Oncology Group (ECOG) performance status 0-1; Child-Pugh score 7 or lower; and adequate bone marrow, liver, and renal function. Patients were randomly assigned (1: 1) via an interactive web response system with a computer-generated sequence to receive 400 mg sorafenib orally twice daily or 400 mg sorafenib orally twice daily plus hepatic arterial infusion chemotherapy (cisplatin 20 mg/m(2) on days 1 and 8 and fluorouracil 330 mg/m(2) continuously on days 1-5 and 8-12 of every 28-day cycle via an implanted catheter system). The primary endpoint was overall survival. The primary efficacy analysis comprised all randomised patients (the intention-to-treat population), and the safety analysis comprised all randomised patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01214343. Findings Between Nov 4, 2010, and June 10, 2014, 206 patients were randomly assigned (103 to the sorafenib group, 103 to the sorafenib plus hepatic arterial infusion chemotherapy group). One patient in the sorafenib plus hepatic arterial infusion chemotherapy group withdrew after randomisation. Median overall survival was similar in the sorafenib plus hepatic arterial infusion chemotherapy (n=102) and sorafenib monotherapy (n=103) groups (11.8 months [95% CI 9.1-14.5] vs 11.5 months [8.2-14.8]; hazard ratio 1.009 [95% CI 0.743-1.371]; p=0.955). Grade 3-4 adverse events that were more frequent in the sorafenib plus hepatic arterial infusion chemotherapy group than in the sorafenib monotherapy group included anaemia (15 [17%] of 88 vs six [6%] of 102), neutropenia (15 [17%] vs one [1%]), thrombocytopenia (30 [34%] vs 12 [12%]), and anorexia (12 [14%] vs six [6%]). Interpretation Addition of hepatic arterial infusion chemotherapy to sorafenib did not significantly improve overall survival in patients with advanced hepatocellular carcinoma. Funding Japanese Ministry of Health, Labour and Welfare. Copyright (c) Elsevier Ltd. All rights reserved.

引用

页码：424 / 432

页数：9

共 27 条

[1] Doxorubicin Plus Sorafenib vs Doxorubicin Alone in Patients With Advanced Hepatocellular Carcinoma A Randomized Trial [J].