PMID- 34250737
OWN - NLM
STAT- MEDLINE
DCOM- 20220303
LR  - 20220303
IS  - 1478-3231 (Electronic)
IS  - 1478-3223 (Linking)
VI  - 41
IP  - 12
DP  - 2021 Dec
TI  - Adverse events as potential predictive factors of activity in patients with 
      advanced hepatocellular carcinoma treated with lenvatinib.
PG  - 2997-3008
LID - 10.1111/liv.15014 [doi]
AB  - BACKGROUND AND AIM: Lenvatinib is a standard of care option in first-line therapy 
      of advanced hepatocellular carcinoma (HCC). In the present study, we aim to 
      identify, in patients with HCC treated with lenvatinib, a possible association 
      between occurrence and grading of adverse events (AEs) and outcome. METHODS: We 
      performed a retrospective analysis of 606 Japanese and Italian patients treated 
      with lenvatinib in first-line setting and investigated the possible correlation 
      between the onset of AEs, toxicity grade (G) and outcome measures such as overall 
      survival (OS) and progression-free survival (PFS). RESULTS: The appearance of 
      arterial hypertension G >/= 2 independently predicted prolonged OS [hazard ratio 
      (HR) 0.66, 95% confidence interval (CI) 0.46-0.93, P = .0188], whereas decreased 
      appetite G >/= 2 independently predicted decreased OS (HR 1.70, 95% CI 1.25-2.32, 
      P = .0007) by multivariate analysis. Appearance of hand-foot skin reaction 
      independently predicted prolonged PFS (HR 0.72, 95% CI 0.56-0.93, P = .0149), 
      whereas decreased appetite G >/= 2 predicted decreased PFS (HR 1.36, 95% CI 
      1.04-1.77, P = .0277). CONCLUSIONS: Our main findings are that the occurrence of 
      arterial hypertension G >/= 2 is a predictor of longer survival, whereas decreased 
      appetite G >/= 2 predicts for a poor prognosis. A careful management of AEs under 
      lenvatinib treatment for HCC is required, to improve patients' quality of life, 
      minimize the need for treatment discontinuation and achieve optimal outcome.
CI  - (c) 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Rapposelli, Ilario Giovanni
AU  - Rapposelli IG
AD  - Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori 
      "Dino Amadori"-IRST, Meldola, Italy.
FAU - Tada, Toshifumi
AU  - Tada T
AUID- ORCID: 0000-0002-0976-6761
AD  - Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, 
      Japan.
FAU - Shimose, Shigeo
AU  - Shimose S
AUID- ORCID: 0000-0003-2068-8386
AD  - Division of Gastroenterology, Department of Medicine, Kurume University School of 
      Medicine, Kurume, Fukuoka, Japan.
FAU - Burgio, Valentina
AU  - Burgio V
AD  - Department of Medical Oncology, San Raffaele Scientific Institute IRCCS, Milan, 
      Italy.
FAU - Kumada, Takashi
AU  - Kumada T
AUID- ORCID: 0000-0003-2211-495X
AD  - Faculty of Nursing, Gifu Kyoritsu University, Ogaki, Japan.
FAU - Iwamoto, Hideki
AU  - Iwamoto H
AD  - Division of Gastroenterology, Department of Medicine, Kurume University School of 
      Medicine, Kurume, Fukuoka, Japan.
FAU - Hiraoka, Atsushi
AU  - Hiraoka A
AUID- ORCID: 0000-0003-1989-0480
AD  - Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan.
FAU - Niizeki, Takashi
AU  - Niizeki T
AD  - Division of Gastroenterology, Department of Medicine, Kurume University School of 
      Medicine, Kurume, Fukuoka, Japan.
FAU - Atsukawa, Masanori
AU  - Atsukawa M
AUID- ORCID: 0000-0003-3374-7111
AD  - Division of Gastroenterology and Hepatology, Department of Internal Medicine, 
      Nippon Medical School, Tokyo, Japan.
FAU - Koga, Hironori
AU  - Koga H
AD  - Division of Gastroenterology, Department of Medicine, Kurume University School of 
      Medicine, Kurume, Fukuoka, Japan.
FAU - Hirooka, Masashi
AU  - Hirooka M
AD  - Department of Gastroenterology and Metabology, Ehime University Graduate School 
      of Medicine, Matsuyama, Japan.
FAU - Torimura, Takuji
AU  - Torimura T
AUID- ORCID: 0000-0002-4863-4278
AD  - Division of Gastroenterology, Department of Medicine, Kurume University School of 
      Medicine, Kurume, Fukuoka, Japan.
FAU - Iavarone, Massimo
AU  - Iavarone M
AD  - Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale 
      Maggiore Policlinico di Milano, Milan, Italy.
FAU - Tortora, Raffaella
AU  - Tortora R
AD  - Liver Unit, Cardarelli Hospital, Naples, Italy.
FAU - Campani, Claudia
AU  - Campani C
AD  - Department of Experimental and Clinical Biomedical Sciences "Mario Serio", 
      University of Florence, Florence, Italy.
FAU - Lonardi, Sara
AU  - Lonardi S
AD  - Early Phase Clinical Trial Unit, Department of Oncology, Veneto Institute of 
      Oncology IOV-IRCCS, Padua, Italy.
AD  - Medical Oncology Unit 1, Department of Oncology, Veneto Institute of Oncology 
      IOV-IRCCS, Padua, Italy.
FAU - Tamburini, Emiliano
AU  - Tamburini E
AD  - Department of Medical Oncology, Card. G. Panico Hospital of Tricase, Tricase, 
      Italy.
FAU - Piscaglia, Fabio
AU  - Piscaglia F
AUID- ORCID: 0000-0001-8264-1845
AD  - Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, Azienda 
      Ospedaliero Universitaria di Bologna, Italy.
FAU - Masi, Gianluca
AU  - Masi G
AD  - Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
FAU - Cabibbo, Giuseppe
AU  - Cabibbo G
AUID- ORCID: 0000-0002-0946-3859
AD  - Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical 
      Specialties, PROMISE, Gastroenterology & Hepatology Unit, University of Palermo, 
      Palermo, Italy.
FAU - Giuseppe Foschi, Francesco
AU  - Giuseppe Foschi F
AD  - Department of Internal Medicine, Faenza Hospital, AUSL Romagna, Faenza, Italy.
FAU - Silletta, Marianna
AU  - Silletta M
AD  - Medical Oncology Unit, University Campus Bio-Medico, Rome, Italy.
FAU - Tsuji, Kunihiko
AU  - Tsuji K
AD  - Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan.
FAU - Ishikawa, Toru
AU  - Ishikawa T
AD  - Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan.
FAU - Takaguchi, Koichi
AU  - Takaguchi K
AD  - Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan.
FAU - Kariyama, Kazuya
AU  - Kariyama K
AD  - Department of Gastroenterology, Okayama City Hospital, Okayama, Japan.
FAU - Itobayashi, Ei
AU  - Itobayashi E
AD  - Department of Gastroenterology, Asahi General Hospital, Asahi, Japan.
FAU - Tajiri, Kazuto
AU  - Tajiri K
AUID- ORCID: 0000-0002-2373-8601
AD  - Department of Gastroenterology, Toyama University Hospital, Toyama, Japan.
FAU - Shimada, Noritomo
AU  - Shimada N
AD  - Division of Gastroenterology and Hepatology, Otakanomori Hospital, Kashiwa, 
      Japan.
FAU - Shibata, Hiroshi
AU  - Shibata H
AD  - Department of Gastroenterology, Tokushima Prefectural Central Hospital, 
      Tokushima, Japan.
FAU - Ochi, Hironori
AU  - Ochi H
AD  - Hepato-biliary Center, Matsuyama Red Cross Hospital, Matsuyama, Japan.
FAU - Yasuda, Satoshi
AU  - Yasuda S
AUID- ORCID: 0000-0002-2266-2414
AD  - Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, 
      Japan.
FAU - Toyoda, Hidenori
AU  - Toyoda H
AUID- ORCID: 0000-0002-1652-6168
AD  - Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, 
      Japan.
FAU - Fukunishi, Shinya
AU  - Fukunishi S
AD  - Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Japan.
FAU - Ohama, Hideko
AU  - Ohama H
AD  - Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Japan.
FAU - Kawata, Kazuhito
AU  - Kawata K
AUID- ORCID: 0000-0002-4986-8578
AD  - Hepatology Division, Department of Internal Medicine, Hamamatsu University School 
      of Medicine, Hamamatsu, Japan.
FAU - Tani, Joji
AU  - Tani J
AD  - Department of Gastroenterology and Neurology, Kagawa University School of 
      Medicine, Kagawa, Japan.
FAU - Nakamura, Shinichiro
AU  - Nakamura S
AD  - Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, 
      Japan.
FAU - Nouso, Kazuhiro
AU  - Nouso K
AUID- ORCID: 0000-0002-2018-0008
AD  - Department of Gastroenterology, Okayama City Hospital, Okayama, Japan.
FAU - Tsutsui, Akemi
AU  - Tsutsui A
AD  - Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan.
FAU - Nagano, Takuya
AU  - Nagano T
AD  - Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan.
FAU - Tanaka, Takaaki
AU  - Tanaka T
AD  - Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan.
FAU - Itokawa, Norio
AU  - Itokawa N
AD  - Division of Gastroenterology and Hepatology, Department of Internal Medicine, 
      Nippon Medical School, Tokyo, Japan.
FAU - Okubo, Tomomi
AU  - Okubo T
AD  - Division of Gastroenterology and Hepatology, Department of Internal Medicine, 
      Nippon Medical School, Tokyo, Japan.
FAU - Arai, Taeang
AU  - Arai T
AD  - Division of Gastroenterology and Hepatology, Department of Internal Medicine, 
      Nippon Medical School, Tokyo, Japan.
FAU - Imai, Michitaka
AU  - Imai M
AD  - Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan.
FAU - Joko, Kouji
AU  - Joko K
AUID- ORCID: 0000-0001-8111-3266
AD  - Hepato-biliary Center, Matsuyama Red Cross Hospital, Matsuyama, Japan.
FAU - Koizumi, Yohei
AU  - Koizumi Y
AD  - Department of Gastroenterology and Metabology, Ehime University Graduate School 
      of Medicine, Matsuyama, Japan.
FAU - Hiasa, Yoichi
AU  - Hiasa Y
AUID- ORCID: 0000-0003-4117-339X
AD  - Department of Gastroenterology and Metabology, Ehime University Graduate School 
      of Medicine, Matsuyama, Japan.
FAU - Rimini, Margherita
AU  - Rimini M
AD  - Division of Oncology, Department of Oncology and Hematology, University Hospital 
      of Modena, Modena, Italy.
FAU - Ratti, Francesca
AU  - Ratti F
AD  - Hepatobiliary Surgery Division, IRCCS San Raffaele Scientific Institute, Milan, 
      Italy.
FAU - Aldrighetti, Luca
AU  - Aldrighetti L
AD  - Hepatobiliary Surgery Division, IRCCS San Raffaele Scientific Institute, Milan, 
      Italy.
FAU - Cascinu, Stefano
AU  - Cascinu S
AD  - Department of Medical Oncology, San Raffaele Scientific Institute IRCCS, Milan, 
      Italy.
AD  - Vita-Salute San Raffaele University, Milan, Italy.
FAU - Casadei-Gardini, Andrea
AU  - Casadei-Gardini A
AUID- ORCID: 0000-0001-7415-5898
AD  - Department of Medical Oncology, San Raffaele Scientific Institute IRCCS, Milan, 
      Italy.
AD  - Vita-Salute San Raffaele University, Milan, Italy.
LA  - eng
PT  - Journal Article
DEP - 20210722
PL  - United States
TA  - Liver Int
JT  - Liver international : official journal of the International Association for the 
      Study of the Liver
JID - 101160857
RN  - 0 (Phenylurea Compounds)
RN  - 0 (Quinolines)
RN  - EE083865G2 (lenvatinib)
SB  - IM
MH  - *Carcinoma, Hepatocellular
MH  - Humans
MH  - *Liver Neoplasms
MH  - Phenylurea Compounds/adverse effects
MH  - Quality of Life
MH  - *Quinolines/adverse effects
MH  - Retrospective Studies
OTO - NOTNLM
OT  - adverse events
OT  - hepatocellular carcinoma
OT  - lenvatinib
OT  - predictive factors
EDAT- 2021/07/13 06:00
MHDA- 2022/03/04 06:00
CRDT- 2021/07/12 06:20
PHST- 2021/07/02 00:00 [revised]
PHST- 2021/05/25 00:00 [received]
PHST- 2021/07/08 00:00 [accepted]
PHST- 2021/07/13 06:00 [pubmed]
PHST- 2022/03/04 06:00 [medline]
PHST- 2021/07/12 06:20 [entrez]
AID - 10.1111/liv.15014 [doi]
PST - ppublish
SO  - Liver Int. 2021 Dec;41(12):2997-3008. doi: 10.1111/liv.15014. Epub 2021 Jul 22.