Clinical development of nintedanib for advanced non-small-cell lung cancer

Masayuki Takeda,1 Isamu Okamoto,2 Kazuhiko Nakagawa1 1Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka, 2Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan Abstract: Angiogenesis is an essential process in t...

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Autores principales:	Takeda M, Okamoto I, Nakagawa K
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/808145f91b5440898b5eefb2a5159d90
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spelling	oai:doaj.org-article:808145f91b5440898b5eefb2a5159d902021-12-02T11:57:17ZClinical development of nintedanib for advanced non-small-cell lung cancer1178-203Xhttps://doaj.org/article/808145f91b5440898b5eefb2a5159d902015-11-01T00:00:00Zhttps://www.dovepress.com/clinical-development-of-nintedanib-for-advanced-non-small-cell-lung-ca-peer-reviewed-article-TCRMhttps://doaj.org/toc/1178-203XMasayuki Takeda,1 Isamu Okamoto,2 Kazuhiko Nakagawa1 1Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka, 2Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan Abstract: Angiogenesis is an essential process in the development, growth, and metastasis of malignant tumors including lung cancer. Several angiogenesis inhibitors have been developed as potential therapies for non-small-cell lung cancer (NSCLC). Nintedanib is a small-molecule tyrosine kinase inhibitor that targets receptors for vascular endothelial growth factor, platelet-derived growth factor, and fibroblast growth factor as well as RET (rearranged during transfection) and Flt3. When administered as monotherapy, nintedanib was well tolerated at doses up to 250 mg or 200 mg twice daily in European and Japanese patients, respectively, with liver toxicity featuring prominently among dose-limiting toxicities in both populations. A recent Phase III trial demonstrated that treatment with the combination of nintedanib and docetaxel resulted in a significant and clinically meaningful improvement in both progression-free survival and overall survival compared with docetaxel alone in predefined NSCLC patients with adenocarcinoma tumor histology. Although the incidence of elevated alanine aminotransferase or aspartate aminotransferase as well as of diarrhea was higher in patients treated with nintedanib plus docetaxel, most of these adverse events were manageable with supportive treatment or dose reduction. The results of completed and ongoing clinical trials of nintedanib monotherapy and combination therapy for the treatment of NSCLC are summarized in this study. Keywords: nintedanib, non-small-cell lung cancer, dose-limiting toxicity, hepatotoxicityTakeda MOkamoto INakagawa KDove Medical PressarticleTherapeutics. PharmacologyRM1-950ENTherapeutics and Clinical Risk Management, Vol 2015, Iss default, Pp 1701-1706 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Therapeutics. Pharmacology RM1-950
spellingShingle	Therapeutics. Pharmacology RM1-950 Takeda M Okamoto I Nakagawa K Clinical development of nintedanib for advanced non-small-cell lung cancer
description	Masayuki Takeda,1 Isamu Okamoto,2 Kazuhiko Nakagawa1 1Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka, 2Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan Abstract: Angiogenesis is an essential process in the development, growth, and metastasis of malignant tumors including lung cancer. Several angiogenesis inhibitors have been developed as potential therapies for non-small-cell lung cancer (NSCLC). Nintedanib is a small-molecule tyrosine kinase inhibitor that targets receptors for vascular endothelial growth factor, platelet-derived growth factor, and fibroblast growth factor as well as RET (rearranged during transfection) and Flt3. When administered as monotherapy, nintedanib was well tolerated at doses up to 250 mg or 200 mg twice daily in European and Japanese patients, respectively, with liver toxicity featuring prominently among dose-limiting toxicities in both populations. A recent Phase III trial demonstrated that treatment with the combination of nintedanib and docetaxel resulted in a significant and clinically meaningful improvement in both progression-free survival and overall survival compared with docetaxel alone in predefined NSCLC patients with adenocarcinoma tumor histology. Although the incidence of elevated alanine aminotransferase or aspartate aminotransferase as well as of diarrhea was higher in patients treated with nintedanib plus docetaxel, most of these adverse events were manageable with supportive treatment or dose reduction. The results of completed and ongoing clinical trials of nintedanib monotherapy and combination therapy for the treatment of NSCLC are summarized in this study. Keywords: nintedanib, non-small-cell lung cancer, dose-limiting toxicity, hepatotoxicity
format	article
author	Takeda M Okamoto I Nakagawa K
author_facet	Takeda M Okamoto I Nakagawa K
author_sort	Takeda M
title	Clinical development of nintedanib for advanced non-small-cell lung cancer
title_short	Clinical development of nintedanib for advanced non-small-cell lung cancer
title_full	Clinical development of nintedanib for advanced non-small-cell lung cancer
title_fullStr	Clinical development of nintedanib for advanced non-small-cell lung cancer
title_full_unstemmed	Clinical development of nintedanib for advanced non-small-cell lung cancer
title_sort	clinical development of nintedanib for advanced non-small-cell lung cancer
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/808145f91b5440898b5eefb2a5159d90
work_keys_str_mv	AT takedam clinicaldevelopmentofnintedanibforadvancednonsmallcelllungcancer AT okamotoi clinicaldevelopmentofnintedanibforadvancednonsmallcelllungcancer AT nakagawak clinicaldevelopmentofnintedanibforadvancednonsmallcelllungcancer
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Clinical development of nintedanib for advanced non-small-cell lung cancer

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