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Lenvatinib, a molecule with versatile application: from preclinical evidence to future development in anti-cancer treatment

Authors Capozzi M, De Divitiis C, Ottaiano A, von Arx C, Scala S, Tatangelo F, Delrio P, Tafuto S

Received 26 September 2018

Accepted for publication 28 February 2019

Published 1 May 2019 Volume 2019:11 Pages 3847—3860

DOI https://doi.org/10.2147/CMAR.S188316

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 3

Editor who approved publication: Dr Beicheng Sun


Monica Capozzi,1 Chiara De Divitiis,2 Alessandro Ottaiano,3 Claudia von Arx,4 Stefania Scala,5 Fabiana Tatangelo,6 Paolo Delrio,1 Salvatore Tafuto1

1Department of Abdominal Oncology, Istituto Nazionale Tumori, IRCCS - Fondazione “G. Pascale”, Napoli, Italia; 2UOSD Oncology- AOU “San Giovanni di Dio e Ruggi D’Aragona”, Salerno, Italia; 3SSD Innovative Therapies for Abdominal Metastases - Department of Abdominal Oncology, Istituto Nazionale Tumori, IRCCS - Fondazione “G. Pascale”, Napoli, Italia; 4Department of Surgery and Cancer, Imperial College London, London, UK; 5Molecular Immunology and Immunoregulation, Istituto Nazionale Tumori, IRCCS - Fondazione “G. Pascale”, Napoli, Italia; 6Department of Pathology, Istituto Nazionale Tumori, IRCCS - Fondazione “G. Pascale”, Napoli, Italia

Abstract: Lenvatinib is an emerging multi-kinase inhibitor with a preferential anti-angiogenic activity, which has shown efficacy in the treatment of renal cell carcinoma, differentiated thyroid cancer and hepatocellular carcinoma. It inhibits vascular endothelial growth factor receptor family (VEGFR1–3), fibroblast growth factor receptor family (FGFR1–4), platelet-derived growth factor receptor–alpha (PDGFRα), tyrosine-kinase receptor (KIT) and rearranged during transfection receptor (RET). In this review we have evaluated the development from bench to bedside of lenvatinib. PubMed, MEDLINE and clinicaltrials.gov are the sources of data. Furthermore, the preclinical in vitro and in vivo data, as well as efficacy and toxicity results of lenvatinib in the clinic, are presented and discussed. Treatment with lenvatinib causes side effects (hypertension, proteinuria, fatigue and diarrhea), which are predominantly related to the inhibition of angiogenesis. For these reasons, the identification of biomarkers of efficacy and resistance to lenvatinib is a key challenge in order to select responsive patients. This review provides an overview on lenvatinib’s clinical use, perspectives and indications for future development.

Keywords: angiogenesis, kinase inhibitors, microvessel density, tumors

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