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FOLFIRI(®) and Bevacizumab in first-line treatment for colorectal cancer patients: safety, efficacy and genetic polymorphisms

BACKGROUND: Over 50% of colorectal cancer (CRC) patients develop metastases. The aim of this study was to evaluate efficacy and tolerance of first-line FOLFIRI® + bevacizumab (B) treatment for metastatic CRC, and to assess genetic polymorphisms as potential markers. METHODS: Adult patients with hist...

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Autores principales: Bécouarn, Yves, Cany, Laurent, Pulido, Marina, Beyssac, Richard, Texereau, Patrick, Le Morvan, Valérie, Béchade, Dominique, Brunet, René, Aitouferoukh, Sofiane, Lalet, Caroline, Mathoulin-Pélissier, Simone, Fonck, Marianne, Robert, Jacques
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4022139/
https://www.ncbi.nlm.nih.gov/pubmed/24758527
http://dx.doi.org/10.1186/1756-0500-7-260
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author Bécouarn, Yves
Cany, Laurent
Pulido, Marina
Beyssac, Richard
Texereau, Patrick
Le Morvan, Valérie
Béchade, Dominique
Brunet, René
Aitouferoukh, Sofiane
Lalet, Caroline
Mathoulin-Pélissier, Simone
Fonck, Marianne
Robert, Jacques
author_facet Bécouarn, Yves
Cany, Laurent
Pulido, Marina
Beyssac, Richard
Texereau, Patrick
Le Morvan, Valérie
Béchade, Dominique
Brunet, René
Aitouferoukh, Sofiane
Lalet, Caroline
Mathoulin-Pélissier, Simone
Fonck, Marianne
Robert, Jacques
author_sort Bécouarn, Yves
collection PubMed
description BACKGROUND: Over 50% of colorectal cancer (CRC) patients develop metastases. The aim of this study was to evaluate efficacy and tolerance of first-line FOLFIRI® + bevacizumab (B) treatment for metastatic CRC, and to assess genetic polymorphisms as potential markers. METHODS: Adult patients with histologically-proven, non-resectable metastatic CRC and ECOG ≤ 2 were included. 14-day cycles consisted of bevacizumab (5 mg/kg), irinotecan (180 mg/m(2)), bolus FU (400 mg/m(2)) and leucovorin (400 mg/m(2)), followed by 46-hour FU infusions (2400 mg/m(2)). Primary endpoint was response rate according to RECIST criteria. Secondary endpoints were overall (OS) and progression-free (PFS) survivals, response duration, and toxicity. Associations between clinical data, UGT1A1, thymidylate synthase, VEGFA polymorphisms and PFS, OS and toxicity were analyzed. RESULTS: Sixty-two patients were enrolled (median age 68y). 59/62 patients were eligible and evaluable for response at 6 months: 28 showed partial response (47.5%; 95% CI; 34.3-60.9), 20 stable disease (33.9%) and 11 progression (18.6%). Grade 3/4 toxicities were as follows: neutropenia 16.1%; diarrhea 11.3%; nausea-vomiting 1.6%. Median response duration was 9.5 months (range 2.7-20); median PFS 10.3 months (range 8.8-11.7); and median OS 25.7 months (range 20.2-29.7). 11/59 initially unresectable patients were resectable after treatment. VEGFA polymorphism (rs25648) was associated with better OS (HR: 3.61; 95% CI: 1.57-8.30). CONCLUSIONS: FOLFIRI® + bevacizumab is active with good response rate, long median OS, and a good safety profile. A VEGFA polymorphism might have a prognostic value in this malignancy. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00467142 (registration date: April 25, 2007)
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spelling pubmed-40221392014-05-16 FOLFIRI(®) and Bevacizumab in first-line treatment for colorectal cancer patients: safety, efficacy and genetic polymorphisms Bécouarn, Yves Cany, Laurent Pulido, Marina Beyssac, Richard Texereau, Patrick Le Morvan, Valérie Béchade, Dominique Brunet, René Aitouferoukh, Sofiane Lalet, Caroline Mathoulin-Pélissier, Simone Fonck, Marianne Robert, Jacques BMC Res Notes Research Article BACKGROUND: Over 50% of colorectal cancer (CRC) patients develop metastases. The aim of this study was to evaluate efficacy and tolerance of first-line FOLFIRI® + bevacizumab (B) treatment for metastatic CRC, and to assess genetic polymorphisms as potential markers. METHODS: Adult patients with histologically-proven, non-resectable metastatic CRC and ECOG ≤ 2 were included. 14-day cycles consisted of bevacizumab (5 mg/kg), irinotecan (180 mg/m(2)), bolus FU (400 mg/m(2)) and leucovorin (400 mg/m(2)), followed by 46-hour FU infusions (2400 mg/m(2)). Primary endpoint was response rate according to RECIST criteria. Secondary endpoints were overall (OS) and progression-free (PFS) survivals, response duration, and toxicity. Associations between clinical data, UGT1A1, thymidylate synthase, VEGFA polymorphisms and PFS, OS and toxicity were analyzed. RESULTS: Sixty-two patients were enrolled (median age 68y). 59/62 patients were eligible and evaluable for response at 6 months: 28 showed partial response (47.5%; 95% CI; 34.3-60.9), 20 stable disease (33.9%) and 11 progression (18.6%). Grade 3/4 toxicities were as follows: neutropenia 16.1%; diarrhea 11.3%; nausea-vomiting 1.6%. Median response duration was 9.5 months (range 2.7-20); median PFS 10.3 months (range 8.8-11.7); and median OS 25.7 months (range 20.2-29.7). 11/59 initially unresectable patients were resectable after treatment. VEGFA polymorphism (rs25648) was associated with better OS (HR: 3.61; 95% CI: 1.57-8.30). CONCLUSIONS: FOLFIRI® + bevacizumab is active with good response rate, long median OS, and a good safety profile. A VEGFA polymorphism might have a prognostic value in this malignancy. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00467142 (registration date: April 25, 2007) BioMed Central 2014-04-23 /pmc/articles/PMC4022139/ /pubmed/24758527 http://dx.doi.org/10.1186/1756-0500-7-260 Text en Copyright © 2014 Bécouarn et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Bécouarn, Yves
Cany, Laurent
Pulido, Marina
Beyssac, Richard
Texereau, Patrick
Le Morvan, Valérie
Béchade, Dominique
Brunet, René
Aitouferoukh, Sofiane
Lalet, Caroline
Mathoulin-Pélissier, Simone
Fonck, Marianne
Robert, Jacques
FOLFIRI(®) and Bevacizumab in first-line treatment for colorectal cancer patients: safety, efficacy and genetic polymorphisms
title FOLFIRI(®) and Bevacizumab in first-line treatment for colorectal cancer patients: safety, efficacy and genetic polymorphisms
title_full FOLFIRI(®) and Bevacizumab in first-line treatment for colorectal cancer patients: safety, efficacy and genetic polymorphisms
title_fullStr FOLFIRI(®) and Bevacizumab in first-line treatment for colorectal cancer patients: safety, efficacy and genetic polymorphisms
title_full_unstemmed FOLFIRI(®) and Bevacizumab in first-line treatment for colorectal cancer patients: safety, efficacy and genetic polymorphisms
title_short FOLFIRI(®) and Bevacizumab in first-line treatment for colorectal cancer patients: safety, efficacy and genetic polymorphisms
title_sort folfiri(®) and bevacizumab in first-line treatment for colorectal cancer patients: safety, efficacy and genetic polymorphisms
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4022139/
https://www.ncbi.nlm.nih.gov/pubmed/24758527
http://dx.doi.org/10.1186/1756-0500-7-260
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