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ID 116246
著者
Kagiwada, Harumi National Institute of Advanced Industrial Science and Technology
Kitazawa, Masashi SOCIUM
Fukui, Kazuhiko National Institute of Advanced Industrial Science and Technology|SOCIUM
Horimoto, Katsuhisa National Institute of Advanced Industrial Science and Technology|SOCIUM
キーワード
hepatocellular carcinoma
lenvatinib
sorafenib
hepatic reserve function
FGFR
資料タイプ
学術雑誌論文
抄録
The efficacy and safety of lenvatinib (LEN) as a second/third-line treatment for unresectable hepatocellular carcinoma (HCC) after sorafenib (SOR) therapy remains unknown. We evaluated the outcomes of second/third-line LEN treatment, investigated the sensitivity of a SOR-resistant HCC cell line (PLC/PRF5-R2) to LEN, and assessed their signal transduction pathways by protein array analysis. We retrospectively enrolled 57 patients with unresectable HCC. Fifty-three radiologically evaluated patients comprised 34 molecular-targeted agent (MTA)-naive (first-line), nine intolerant to SOR (second-line), and 10 resistant to regorafenib (third-line). The objective response rates (ORRs) were 61.8% in first-line, 33.3% in second-line, and 20.0% in third-line groups. The overall survival (OS) in the first-line was significantly longer than that in the third-line group (p < 0.05). Patients with better liver functional reserves (child score, ALBI grade) exhibited higher ORR and longer OS. The IC50 of LEN against PLC/PRF5-R2 was significantly higher than that against PLC/PRF5. LEN significantly inhibited more LEN-related signal transduction pathways in PLC/PRF5 than in PLC/PRF5-R2 cells. This suggests that LEN is active and safe as a second/third-line treatment for unresectable HCC. LEN seems more effective for patients with HCC with better hepatic reserve functions or before MTA-resistance is acquired because of the partial cross-resistance to SOR.
掲載誌名
Oncotarget
ISSN
19492553
出版者
Impact Journals
11
26
開始ページ
2531
終了ページ
2542
発行日
2020-06-30
権利情報
This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0)(https://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
病院
医学系