Abstract | BACKGROUND: 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/m2 on days 1 and 8 and fluorouracil 330 mg/m2 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: FUNDING: Japanese Ministry of Health, Labour and Welfare.
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Authors | Masatoshi Kudo, Kazuomi Ueshima, Osamu Yokosuka, Sadahisa Ogasawara, Shuntaro Obi, Namiki Izumi, Hiroshi Aikata, Hiroaki Nagano, Etsuro Hatano, Yutaka Sasaki, Keisuke Hino, Takashi Kumada, Kazuhide Yamamoto, Yasuharu Imai, Shouta Iwadou, Chikara Ogawa, Takuji Okusaka, Fumihiko Kanai, Kohei Akazawa, Ken-Ichi Yoshimura, Philip Johnson, Yasuaki Arai, SILIUS study group |
Journal | The lancet. Gastroenterology & hepatology
(Lancet Gastroenterol Hepatol)
Vol. 3
Issue 6
Pg. 424-432
(06 2018)
ISSN: 2468-1253 [Electronic] Netherlands |
PMID | 29631810
(Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2018 Elsevier Ltd. All rights reserved. |
Chemical References |
- Sorafenib
- Cisplatin
- Fluorouracil
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Topics |
- Aged
- Antineoplastic Combined Chemotherapy Protocols
(adverse effects, therapeutic use)
- Carcinoma, Hepatocellular
(drug therapy, mortality)
- Cisplatin
(administration & dosage, adverse effects)
- Disease Progression
- Disease-Free Survival
- Female
- Fluorouracil
(administration & dosage, adverse effects)
- Hepatic Artery
- Humans
- Infusions, Intra-Arterial
- Intention to Treat Analysis
- Liver Neoplasms
(drug therapy, mortality)
- Male
- Middle Aged
- Sorafenib
(administration & dosage, adverse effects)
- Survival Analysis
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