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Phase II trial of modified FOLFOX6 and erlotinib in patients with metastatic or advanced adenocarcinoma of the oesophagus and gastro-oesophageal junction

BACKGROUND: There is increased recognition that cancers of the upper GI tract comprise distinct epidemiological and molecular entities. Erlotinib has shown activity in patients with adenocarcinoma of the oesophagus/gastro-oesophageal junction (GEJ), but not in distal gastric cancer. mFOLFOX6 is one...

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Autores principales: Wainberg, Z A, Lin, L-S, DiCarlo, B, Dao, K M, Patel, R, Park, D J, Wang, H-J, Elashoff, R, Ryba, N, Hecht, J R
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3171005/
https://www.ncbi.nlm.nih.gov/pubmed/21811258
http://dx.doi.org/10.1038/bjc.2011.280
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author Wainberg, Z A
Lin, L-S
DiCarlo, B
Dao, K M
Patel, R
Park, D J
Wang, H-J
Elashoff, R
Ryba, N
Hecht, J R
author_facet Wainberg, Z A
Lin, L-S
DiCarlo, B
Dao, K M
Patel, R
Park, D J
Wang, H-J
Elashoff, R
Ryba, N
Hecht, J R
author_sort Wainberg, Z A
collection PubMed
description BACKGROUND: There is increased recognition that cancers of the upper GI tract comprise distinct epidemiological and molecular entities. Erlotinib has shown activity in patients with adenocarcinoma of the oesophagus/gastro-oesophageal junction (GEJ), but not in distal gastric cancer. mFOLFOX6 is one of several active regimens used to treat adenocarcinoma of the Eso/GEJ. This study evaluates the efficacy and safety of mFOLFOX6 and erlotinib in patients with metastatic or advanced Eso/GEJ cancers. METHODS: Patients with previously untreated advanced or metastatic Eso/GEJ adenocarcinoma are treated with oxaliplatin 85 mg m(–2), 5-FU 400 mg m(–2), LV 400 mg m(–2) on day 1, 5-FU 2400 mg m(–2) over 48 h and erlotinib 150 mg PO daily. Treatment was repeated every 14 days. The primary objective was response rate (RR), secondary objectives include toxicity, progression-free survival (PFS), overall survival (OS) and to correlate clinical outcome with expression patterns and molecular alterations in the epidermal growth factor receptor-dependent pathways. RESULTS: A total of 33 patients were treated and evaluable: there were two complete responses, 15 partial responses for an objective RR of 51.5% (95% CI, 34.5–68.6%). Median PFS was 5.5 months (95% CI, 3.1–7.5 months) and median OS was 11.0 months (95% CI, 8.0–17.4 months). The most common grade 3–4 toxicities were: diarrhoea (24%), nausea/vomiting (11%), skin rash (8%) and peripheral neuropathy (8%). The frequency of alterations was KRAS mutations (8%), EGFR mutations (0%) and HER2 amplification (19%). CONCLUSION: In patients with Eso/GEJ adenocarcinoma, mFOLFOX6 and erlotinib is active, has an acceptable toxicity profile and FOLFOX±erlotinib could be considered for further development.
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spelling pubmed-31710052012-09-06 Phase II trial of modified FOLFOX6 and erlotinib in patients with metastatic or advanced adenocarcinoma of the oesophagus and gastro-oesophageal junction Wainberg, Z A Lin, L-S DiCarlo, B Dao, K M Patel, R Park, D J Wang, H-J Elashoff, R Ryba, N Hecht, J R Br J Cancer Clinical Study BACKGROUND: There is increased recognition that cancers of the upper GI tract comprise distinct epidemiological and molecular entities. Erlotinib has shown activity in patients with adenocarcinoma of the oesophagus/gastro-oesophageal junction (GEJ), but not in distal gastric cancer. mFOLFOX6 is one of several active regimens used to treat adenocarcinoma of the Eso/GEJ. This study evaluates the efficacy and safety of mFOLFOX6 and erlotinib in patients with metastatic or advanced Eso/GEJ cancers. METHODS: Patients with previously untreated advanced or metastatic Eso/GEJ adenocarcinoma are treated with oxaliplatin 85 mg m(–2), 5-FU 400 mg m(–2), LV 400 mg m(–2) on day 1, 5-FU 2400 mg m(–2) over 48 h and erlotinib 150 mg PO daily. Treatment was repeated every 14 days. The primary objective was response rate (RR), secondary objectives include toxicity, progression-free survival (PFS), overall survival (OS) and to correlate clinical outcome with expression patterns and molecular alterations in the epidermal growth factor receptor-dependent pathways. RESULTS: A total of 33 patients were treated and evaluable: there were two complete responses, 15 partial responses for an objective RR of 51.5% (95% CI, 34.5–68.6%). Median PFS was 5.5 months (95% CI, 3.1–7.5 months) and median OS was 11.0 months (95% CI, 8.0–17.4 months). The most common grade 3–4 toxicities were: diarrhoea (24%), nausea/vomiting (11%), skin rash (8%) and peripheral neuropathy (8%). The frequency of alterations was KRAS mutations (8%), EGFR mutations (0%) and HER2 amplification (19%). CONCLUSION: In patients with Eso/GEJ adenocarcinoma, mFOLFOX6 and erlotinib is active, has an acceptable toxicity profile and FOLFOX±erlotinib could be considered for further development. Nature Publishing Group 2011-09-06 2011-08-02 /pmc/articles/PMC3171005/ /pubmed/21811258 http://dx.doi.org/10.1038/bjc.2011.280 Text en Copyright © 2011 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Clinical Study
Wainberg, Z A
Lin, L-S
DiCarlo, B
Dao, K M
Patel, R
Park, D J
Wang, H-J
Elashoff, R
Ryba, N
Hecht, J R
Phase II trial of modified FOLFOX6 and erlotinib in patients with metastatic or advanced adenocarcinoma of the oesophagus and gastro-oesophageal junction
title Phase II trial of modified FOLFOX6 and erlotinib in patients with metastatic or advanced adenocarcinoma of the oesophagus and gastro-oesophageal junction
title_full Phase II trial of modified FOLFOX6 and erlotinib in patients with metastatic or advanced adenocarcinoma of the oesophagus and gastro-oesophageal junction
title_fullStr Phase II trial of modified FOLFOX6 and erlotinib in patients with metastatic or advanced adenocarcinoma of the oesophagus and gastro-oesophageal junction
title_full_unstemmed Phase II trial of modified FOLFOX6 and erlotinib in patients with metastatic or advanced adenocarcinoma of the oesophagus and gastro-oesophageal junction
title_short Phase II trial of modified FOLFOX6 and erlotinib in patients with metastatic or advanced adenocarcinoma of the oesophagus and gastro-oesophageal junction
title_sort phase ii trial of modified folfox6 and erlotinib in patients with metastatic or advanced adenocarcinoma of the oesophagus and gastro-oesophageal junction
topic Clinical Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3171005/
https://www.ncbi.nlm.nih.gov/pubmed/21811258
http://dx.doi.org/10.1038/bjc.2011.280
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