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An open-label feasibility study of nintedanib combined with docetaxel in Japanese patients with locally advanced or metastatic lung adenocarcinoma after failure of first-line chemotherapy

PURPOSE: This open-label feasibility study assessed the tolerability of nintedanib 200 mg in combination with docetaxel 75 mg/m(2) as a starting dose in Japanese patients with a body surface area (BSA) < 1.5 m(2) and locally advanced or metastatic lung adenocarcinoma. METHODS: Eligible patients r...

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Autores principales: Yamamoto, Noboru, Kenmotsu, Hirotsugu, Goto, Koichi, Takeda, Koji, Kato, Terufumi, Takeda, Masayuki, Horinouchi, Hidehito, Saito, Isao, Sarashina, Akiko, Tanaka, Tetsuya, Morsli, Nassim, Nakagawa, Kazuhiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6132853/
https://www.ncbi.nlm.nih.gov/pubmed/30073583
http://dx.doi.org/10.1007/s00280-018-3649-x
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author Yamamoto, Noboru
Kenmotsu, Hirotsugu
Goto, Koichi
Takeda, Koji
Kato, Terufumi
Takeda, Masayuki
Horinouchi, Hidehito
Saito, Isao
Sarashina, Akiko
Tanaka, Tetsuya
Morsli, Nassim
Nakagawa, Kazuhiko
author_facet Yamamoto, Noboru
Kenmotsu, Hirotsugu
Goto, Koichi
Takeda, Koji
Kato, Terufumi
Takeda, Masayuki
Horinouchi, Hidehito
Saito, Isao
Sarashina, Akiko
Tanaka, Tetsuya
Morsli, Nassim
Nakagawa, Kazuhiko
author_sort Yamamoto, Noboru
collection PubMed
description PURPOSE: This open-label feasibility study assessed the tolerability of nintedanib 200 mg in combination with docetaxel 75 mg/m(2) as a starting dose in Japanese patients with a body surface area (BSA) < 1.5 m(2) and locally advanced or metastatic lung adenocarcinoma. METHODS: Eligible patients received docetaxel 75 mg/m(2) every 21 days and nintedanib administered at 200 mg twice daily (bid), starting on day 2 of each cycle. Treatment was continued until disease progression or undue toxicity. The primary endpoint was the number of patients experiencing dose-limiting toxicities (DLTs) in cycle 1 (days 1–21). RESULTS: Of 10 treated patients, 2 patients (20%) experienced DLTs during cycle 1. These DLTs were grade 3 liver enzyme elevations [alanine aminotransferase (2 patients) and aspartate aminotransferase (2 patients)], and grade 2 hyperbilirubinemia (1 patient). Nine patients met the predefined criteria for nintedanib 200 mg bid plus docetaxel 75 mg/m(2) to be considered a tolerable starting dose. All patients experienced ≥ 1 adverse event (AE) during the treatment period (all drug-related), but no patients experienced AEs that led to discontinuation of nintedanib. Of the five serious AEs reported during treatment, none were drug-related. There was no apparent effect of nintedanib on the pharmacokinetics of docetaxel. The objective response and disease control rates were 40 and 70%, respectively. CONCLUSION: Nintedanib 200 mg bid plus docetaxel 75 mg/m(2) is a tolerable starting dose in Japanese patients with a BSA < 1.5 m(2) with locally advanced or metastatic lung adenocarcinoma. CLINICALTRIALS.GOV NUMBER: NCT02300298.
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spelling pubmed-61328532018-09-13 An open-label feasibility study of nintedanib combined with docetaxel in Japanese patients with locally advanced or metastatic lung adenocarcinoma after failure of first-line chemotherapy Yamamoto, Noboru Kenmotsu, Hirotsugu Goto, Koichi Takeda, Koji Kato, Terufumi Takeda, Masayuki Horinouchi, Hidehito Saito, Isao Sarashina, Akiko Tanaka, Tetsuya Morsli, Nassim Nakagawa, Kazuhiko Cancer Chemother Pharmacol Original Article PURPOSE: This open-label feasibility study assessed the tolerability of nintedanib 200 mg in combination with docetaxel 75 mg/m(2) as a starting dose in Japanese patients with a body surface area (BSA) < 1.5 m(2) and locally advanced or metastatic lung adenocarcinoma. METHODS: Eligible patients received docetaxel 75 mg/m(2) every 21 days and nintedanib administered at 200 mg twice daily (bid), starting on day 2 of each cycle. Treatment was continued until disease progression or undue toxicity. The primary endpoint was the number of patients experiencing dose-limiting toxicities (DLTs) in cycle 1 (days 1–21). RESULTS: Of 10 treated patients, 2 patients (20%) experienced DLTs during cycle 1. These DLTs were grade 3 liver enzyme elevations [alanine aminotransferase (2 patients) and aspartate aminotransferase (2 patients)], and grade 2 hyperbilirubinemia (1 patient). Nine patients met the predefined criteria for nintedanib 200 mg bid plus docetaxel 75 mg/m(2) to be considered a tolerable starting dose. All patients experienced ≥ 1 adverse event (AE) during the treatment period (all drug-related), but no patients experienced AEs that led to discontinuation of nintedanib. Of the five serious AEs reported during treatment, none were drug-related. There was no apparent effect of nintedanib on the pharmacokinetics of docetaxel. The objective response and disease control rates were 40 and 70%, respectively. CONCLUSION: Nintedanib 200 mg bid plus docetaxel 75 mg/m(2) is a tolerable starting dose in Japanese patients with a BSA < 1.5 m(2) with locally advanced or metastatic lung adenocarcinoma. CLINICALTRIALS.GOV NUMBER: NCT02300298. Springer Berlin Heidelberg 2018-08-03 2018 /pmc/articles/PMC6132853/ /pubmed/30073583 http://dx.doi.org/10.1007/s00280-018-3649-x Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Article
Yamamoto, Noboru
Kenmotsu, Hirotsugu
Goto, Koichi
Takeda, Koji
Kato, Terufumi
Takeda, Masayuki
Horinouchi, Hidehito
Saito, Isao
Sarashina, Akiko
Tanaka, Tetsuya
Morsli, Nassim
Nakagawa, Kazuhiko
An open-label feasibility study of nintedanib combined with docetaxel in Japanese patients with locally advanced or metastatic lung adenocarcinoma after failure of first-line chemotherapy
title An open-label feasibility study of nintedanib combined with docetaxel in Japanese patients with locally advanced or metastatic lung adenocarcinoma after failure of first-line chemotherapy
title_full An open-label feasibility study of nintedanib combined with docetaxel in Japanese patients with locally advanced or metastatic lung adenocarcinoma after failure of first-line chemotherapy
title_fullStr An open-label feasibility study of nintedanib combined with docetaxel in Japanese patients with locally advanced or metastatic lung adenocarcinoma after failure of first-line chemotherapy
title_full_unstemmed An open-label feasibility study of nintedanib combined with docetaxel in Japanese patients with locally advanced or metastatic lung adenocarcinoma after failure of first-line chemotherapy
title_short An open-label feasibility study of nintedanib combined with docetaxel in Japanese patients with locally advanced or metastatic lung adenocarcinoma after failure of first-line chemotherapy
title_sort open-label feasibility study of nintedanib combined with docetaxel in japanese patients with locally advanced or metastatic lung adenocarcinoma after failure of first-line chemotherapy
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6132853/
https://www.ncbi.nlm.nih.gov/pubmed/30073583
http://dx.doi.org/10.1007/s00280-018-3649-x
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