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Phase I study of afatinib combined with nintedanib in patients with advanced solid tumours
BACKGROUND: This Phase I study evaluated continuous- and intermittent-dosing (every other week) of afatinib plus nintedanib in patients with advanced solid tumours. METHODS: In the dose-escalation phase (n=45), maximum tolerated doses (MTDs) were determined for continuous/intermittent afatinib 10, 2...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4815889/ https://www.ncbi.nlm.nih.gov/pubmed/26512876 http://dx.doi.org/10.1038/bjc.2015.374 |
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author | Bahleda, Rastislav Hollebecque, Antoine Varga, Andrea Gazzah, Anas Massard, Christophe Deutsch, Eric Amellal, Nadia Farace, Françoise Ould-Kaci, Mahmoud Roux, Flavien Marzin, Kristell Soria, Jean-Charles |
author_facet | Bahleda, Rastislav Hollebecque, Antoine Varga, Andrea Gazzah, Anas Massard, Christophe Deutsch, Eric Amellal, Nadia Farace, Françoise Ould-Kaci, Mahmoud Roux, Flavien Marzin, Kristell Soria, Jean-Charles |
author_sort | Bahleda, Rastislav |
collection | PubMed |
description | BACKGROUND: This Phase I study evaluated continuous- and intermittent-dosing (every other week) of afatinib plus nintedanib in patients with advanced solid tumours. METHODS: In the dose-escalation phase (n=45), maximum tolerated doses (MTDs) were determined for continuous/intermittent afatinib 10, 20, 30 or 40 mg once daily plus continuous nintedanib 150 or 200 mg twice daily. Secondary objectives included safety and efficacy. Clinical activity of continuous afatinib plus nintedanib at the MTD was further evaluated in an expansion phase (n=25). RESULTS: The most frequent dose-limiting toxicities were diarrhoea (11%) and transaminase elevations (7%). Maximum tolerated doses were afatinib 30 mg continuously plus nintedanib 150 mg, and afatinib 40 mg intermittently plus nintedanib 150 mg. Treatment-related adverse events (mostly Grade ⩽3) included diarrhoea (98%), asthenia (64%), nausea (62%) and vomiting (60%). In the dose-escalation phase, two patients had partial responses (PRs) and 27 (60%) had stable disease (SD). In the expansion phase, one complete response and three PRs were observed (all non-small cell lung cancer), with SD in 13 (52%) patients. No pharmacokinetic interactions were observed. CONCLUSIONS: MTDs of continuous or intermittent afatinib plus nintedanib demonstrated a manageable safety profile with proactive management of diarrhoea. Antitumour activity was observed in patients with solid tumours. |
format | Online Article Text |
id | pubmed-4815889 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-48158892016-04-13 Phase I study of afatinib combined with nintedanib in patients with advanced solid tumours Bahleda, Rastislav Hollebecque, Antoine Varga, Andrea Gazzah, Anas Massard, Christophe Deutsch, Eric Amellal, Nadia Farace, Françoise Ould-Kaci, Mahmoud Roux, Flavien Marzin, Kristell Soria, Jean-Charles Br J Cancer Clinical Study BACKGROUND: This Phase I study evaluated continuous- and intermittent-dosing (every other week) of afatinib plus nintedanib in patients with advanced solid tumours. METHODS: In the dose-escalation phase (n=45), maximum tolerated doses (MTDs) were determined for continuous/intermittent afatinib 10, 20, 30 or 40 mg once daily plus continuous nintedanib 150 or 200 mg twice daily. Secondary objectives included safety and efficacy. Clinical activity of continuous afatinib plus nintedanib at the MTD was further evaluated in an expansion phase (n=25). RESULTS: The most frequent dose-limiting toxicities were diarrhoea (11%) and transaminase elevations (7%). Maximum tolerated doses were afatinib 30 mg continuously plus nintedanib 150 mg, and afatinib 40 mg intermittently plus nintedanib 150 mg. Treatment-related adverse events (mostly Grade ⩽3) included diarrhoea (98%), asthenia (64%), nausea (62%) and vomiting (60%). In the dose-escalation phase, two patients had partial responses (PRs) and 27 (60%) had stable disease (SD). In the expansion phase, one complete response and three PRs were observed (all non-small cell lung cancer), with SD in 13 (52%) patients. No pharmacokinetic interactions were observed. CONCLUSIONS: MTDs of continuous or intermittent afatinib plus nintedanib demonstrated a manageable safety profile with proactive management of diarrhoea. Antitumour activity was observed in patients with solid tumours. Nature Publishing Group 2015-11-17 2015-10-29 /pmc/articles/PMC4815889/ /pubmed/26512876 http://dx.doi.org/10.1038/bjc.2015.374 Text en Copyright © 2015 Cancer Research UK http://creativecommons.org/licenses/by/4.0/ This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Clinical Study Bahleda, Rastislav Hollebecque, Antoine Varga, Andrea Gazzah, Anas Massard, Christophe Deutsch, Eric Amellal, Nadia Farace, Françoise Ould-Kaci, Mahmoud Roux, Flavien Marzin, Kristell Soria, Jean-Charles Phase I study of afatinib combined with nintedanib in patients with advanced solid tumours |
title | Phase I study of afatinib combined with nintedanib in patients with advanced solid tumours |
title_full | Phase I study of afatinib combined with nintedanib in patients with advanced solid tumours |
title_fullStr | Phase I study of afatinib combined with nintedanib in patients with advanced solid tumours |
title_full_unstemmed | Phase I study of afatinib combined with nintedanib in patients with advanced solid tumours |
title_short | Phase I study of afatinib combined with nintedanib in patients with advanced solid tumours |
title_sort | phase i study of afatinib combined with nintedanib in patients with advanced solid tumours |
topic | Clinical Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4815889/ https://www.ncbi.nlm.nih.gov/pubmed/26512876 http://dx.doi.org/10.1038/bjc.2015.374 |
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