論文

査読有り 国際誌
2018年6月

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.

The lancet. Gastroenterology & hepatology
  • 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
  • 全て表示

3
6
開始ページ
424
終了ページ
432
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/S2468-1253(18)30078-5

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/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: 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.

リンク情報
DOI
https://doi.org/10.1016/S2468-1253(18)30078-5
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29631810
ID情報
  • DOI : 10.1016/S2468-1253(18)30078-5
  • PubMed ID : 29631810

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