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Temozolomide and Bevacizumab Induction before Chemoradiotherapy in Patients with Bulky Glioblastoma and/or with Severe Neurological Impairment

Background.New approaches are needed for patients newly diagnosed with bulky glioblastoma (GB) and/or with severe neurological impairment that cannot benefit from first line temozolomide (TMZ)-based chemoradiotherapy. Bevacizumab (BEV), an antiangiogenic anti-VEGF-R monoclonal antibody, has a rapid...

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Autores principales: Darmon, Ilan, Morisse, Mony Chenda, Coutte, Alexandre, Blonski, Marie, Le Rhun, Emilie, Taillandier, Luc, Roufai, Diana Bello, Desenclos, Christine, Trudel, Stéphanie, Faivre, Jean-Christophe, Blanchard, Nicolas, Chauffert, Bruno, Boone, Mathieu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5479247/
https://www.ncbi.nlm.nih.gov/pubmed/28638456
http://dx.doi.org/10.7150/jca.18339
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author Darmon, Ilan
Morisse, Mony Chenda
Coutte, Alexandre
Blonski, Marie
Le Rhun, Emilie
Taillandier, Luc
Roufai, Diana Bello
Desenclos, Christine
Trudel, Stéphanie
Faivre, Jean-Christophe
Blanchard, Nicolas
Chauffert, Bruno
Boone, Mathieu
author_facet Darmon, Ilan
Morisse, Mony Chenda
Coutte, Alexandre
Blonski, Marie
Le Rhun, Emilie
Taillandier, Luc
Roufai, Diana Bello
Desenclos, Christine
Trudel, Stéphanie
Faivre, Jean-Christophe
Blanchard, Nicolas
Chauffert, Bruno
Boone, Mathieu
author_sort Darmon, Ilan
collection PubMed
description Background.New approaches are needed for patients newly diagnosed with bulky glioblastoma (GB) and/or with severe neurological impairment that cannot benefit from first line temozolomide (TMZ)-based chemoradiotherapy. Bevacizumab (BEV), an antiangiogenic anti-VEGF-R monoclonal antibody, has a rapid impact on tumor-related brain edema in recurrent GB. The present study reports the feasibility and efficacy of an induction treatment with TMZ and BEV to alleviate the initial neurological impairment and/or to reduce the tumor volume before a delayed chemoradiotherapy. Methods.We retrospectively analyzed tumor and target volumes and clinical neurological status in 39 patients with bulky GB and/or with severe neurological impairment after an induction treatment combining TMZ and BEV. Neurological and radiological responses were assessed according to RANO criteria. Calculating gross tumor and clinical target volumes (GTV and CTV) was done at diagnosis and before radiotherapy. Progression-free survival (PFS) and overall survival (OS) were determined by Kaplan Meier methods. Safety was reported according to NCTCAE. Results. A cohort of 39 patients was analyzed between December 2010 and April 2014. Upfront standard TMZ-based chemoradiotherapy was recused due either to tumor volume or impairment of neurological status and/or performance status. After TMZ/BEV induction (median time of 3 months), 6 (15%) patients achieved a partial response (PR), and 17 (44%) had a stable disease. 24 patients (62%) received a radical-intent chemoradiotherapy. TMZ-BEV induced median reduction of the clinical target volume (CTV) was 25.9% [-84.4%; - 4.8%]. The median PFS and OS were 8.4 months [95% CI: (6.6 - 9.9)] and 11.0 months [95% CI: (9.3 - 13.7)], respectively in the whole cohort and 10.8 [95% CI: (9.3 - 12.9)] and 15.0 [95% CI: (13.2 - 17.8)] for irradiated patients. Induction treatment led to corticosteroid dose reduction or cessation in 21 patients (54%). KPS improvement was observed in 38% of patients. Toxicity was mild with only 7/39 (18%) grade III-IV toxicity, including 1 digestive bleeding and 1 epistaxis. Conclusion.TMZ-BEV induction led to CTV reduction allowing for optimal chemoradiotherapy in a majority (62%) of patients for which radiotherapy was initially recused. A clinical benefit was obtained with improved KPS and a decrease in steroid dose.
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spelling pubmed-54792472017-06-21 Temozolomide and Bevacizumab Induction before Chemoradiotherapy in Patients with Bulky Glioblastoma and/or with Severe Neurological Impairment Darmon, Ilan Morisse, Mony Chenda Coutte, Alexandre Blonski, Marie Le Rhun, Emilie Taillandier, Luc Roufai, Diana Bello Desenclos, Christine Trudel, Stéphanie Faivre, Jean-Christophe Blanchard, Nicolas Chauffert, Bruno Boone, Mathieu J Cancer Research Paper Background.New approaches are needed for patients newly diagnosed with bulky glioblastoma (GB) and/or with severe neurological impairment that cannot benefit from first line temozolomide (TMZ)-based chemoradiotherapy. Bevacizumab (BEV), an antiangiogenic anti-VEGF-R monoclonal antibody, has a rapid impact on tumor-related brain edema in recurrent GB. The present study reports the feasibility and efficacy of an induction treatment with TMZ and BEV to alleviate the initial neurological impairment and/or to reduce the tumor volume before a delayed chemoradiotherapy. Methods.We retrospectively analyzed tumor and target volumes and clinical neurological status in 39 patients with bulky GB and/or with severe neurological impairment after an induction treatment combining TMZ and BEV. Neurological and radiological responses were assessed according to RANO criteria. Calculating gross tumor and clinical target volumes (GTV and CTV) was done at diagnosis and before radiotherapy. Progression-free survival (PFS) and overall survival (OS) were determined by Kaplan Meier methods. Safety was reported according to NCTCAE. Results. A cohort of 39 patients was analyzed between December 2010 and April 2014. Upfront standard TMZ-based chemoradiotherapy was recused due either to tumor volume or impairment of neurological status and/or performance status. After TMZ/BEV induction (median time of 3 months), 6 (15%) patients achieved a partial response (PR), and 17 (44%) had a stable disease. 24 patients (62%) received a radical-intent chemoradiotherapy. TMZ-BEV induced median reduction of the clinical target volume (CTV) was 25.9% [-84.4%; - 4.8%]. The median PFS and OS were 8.4 months [95% CI: (6.6 - 9.9)] and 11.0 months [95% CI: (9.3 - 13.7)], respectively in the whole cohort and 10.8 [95% CI: (9.3 - 12.9)] and 15.0 [95% CI: (13.2 - 17.8)] for irradiated patients. Induction treatment led to corticosteroid dose reduction or cessation in 21 patients (54%). KPS improvement was observed in 38% of patients. Toxicity was mild with only 7/39 (18%) grade III-IV toxicity, including 1 digestive bleeding and 1 epistaxis. Conclusion.TMZ-BEV induction led to CTV reduction allowing for optimal chemoradiotherapy in a majority (62%) of patients for which radiotherapy was initially recused. A clinical benefit was obtained with improved KPS and a decrease in steroid dose. Ivyspring International Publisher 2017-05-12 /pmc/articles/PMC5479247/ /pubmed/28638456 http://dx.doi.org/10.7150/jca.18339 Text en © Ivyspring International Publisher This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Darmon, Ilan
Morisse, Mony Chenda
Coutte, Alexandre
Blonski, Marie
Le Rhun, Emilie
Taillandier, Luc
Roufai, Diana Bello
Desenclos, Christine
Trudel, Stéphanie
Faivre, Jean-Christophe
Blanchard, Nicolas
Chauffert, Bruno
Boone, Mathieu
Temozolomide and Bevacizumab Induction before Chemoradiotherapy in Patients with Bulky Glioblastoma and/or with Severe Neurological Impairment
title Temozolomide and Bevacizumab Induction before Chemoradiotherapy in Patients with Bulky Glioblastoma and/or with Severe Neurological Impairment
title_full Temozolomide and Bevacizumab Induction before Chemoradiotherapy in Patients with Bulky Glioblastoma and/or with Severe Neurological Impairment
title_fullStr Temozolomide and Bevacizumab Induction before Chemoradiotherapy in Patients with Bulky Glioblastoma and/or with Severe Neurological Impairment
title_full_unstemmed Temozolomide and Bevacizumab Induction before Chemoradiotherapy in Patients with Bulky Glioblastoma and/or with Severe Neurological Impairment
title_short Temozolomide and Bevacizumab Induction before Chemoradiotherapy in Patients with Bulky Glioblastoma and/or with Severe Neurological Impairment
title_sort temozolomide and bevacizumab induction before chemoradiotherapy in patients with bulky glioblastoma and/or with severe neurological impairment
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5479247/
https://www.ncbi.nlm.nih.gov/pubmed/28638456
http://dx.doi.org/10.7150/jca.18339
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