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DIPG-82. CLINICAL EXPERIENCE OF CONVECTION ENHANCED DELIVERY (CED) OF CARBOPLATIN AND SODIUM VALPROATE INTO THE PONS FOR THE TREATMENT OF DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG) IN CHILDREN AND YOUNG ADULTS AFTER RADIOTHERAPY

PURPOSE: Effective treatment of diffuse intrinsic pontine glioma (DIPG) remains a formidable challenge due to inadequate penetration of the blood-brain barrier (BBB) by systemically administered chemotherapies. The BBB can be overcome by directly infusing drugs into pons using method of convection-e...

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Autores principales: Szychot, Elwira, Walker, David, Collins, Peter, Hyare, Harpreet, Shankar, Ananth, Bienemann, Alison, Hollingworth, Milo, Gill, Steven
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7715416/
http://dx.doi.org/10.1093/neuonc/noaa222.123
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author Szychot, Elwira
Walker, David
Collins, Peter
Hyare, Harpreet
Shankar, Ananth
Bienemann, Alison
Hollingworth, Milo
Gill, Steven
author_facet Szychot, Elwira
Walker, David
Collins, Peter
Hyare, Harpreet
Shankar, Ananth
Bienemann, Alison
Hollingworth, Milo
Gill, Steven
author_sort Szychot, Elwira
collection PubMed
description PURPOSE: Effective treatment of diffuse intrinsic pontine glioma (DIPG) remains a formidable challenge due to inadequate penetration of the blood-brain barrier (BBB) by systemically administered chemotherapies. The BBB can be overcome by directly infusing drugs into pons using method of convection-enhanced delivery (CED). We describe our clinical experience and what we have learned about the safety and feasibility of treating DIPG with intermittent CED of carboplatin and sodium valproate to the pons through the Renishaw Drug Delivery System (RDDS). METHODS: Retrospective review (2017–2020) of children with DIPG, who following radiotherapy, received compassionate treatment commencing 3.3–10 months post diagnosis (median 4.9 months). They received up to 7 cycles of 3–6 weekly pontine infusions of carboplatin (0.12-0.18mg/ml) and sodium valproate (14.4- 28.8mg/ml). RESULTS: 13 children 3–19 years (mean 6.9 years) were treated. There were no surgical complications. With the exception of infusion channels blocking in one device there were no adverse device effects. Two patients developed persistent 6(th) nerve palsies, which led to drug concentration reduction in the combination therapy. Subsequently infusion/ drug related toxicities were transient. Tumour was controlled in pons in 11/13 patients. Median progression free survival (PFS) was 13.0 months, while median overall survival (OS) was 15.3 months. CONCLUSIONS: Use of the RDDS was safe and well tolerated in all 13 patients. Treatment improved control of pontine disease resulting in longer PFS and OS than reported for conventional therapy and merits further evaluation in a clinical trial.
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spelling pubmed-77154162020-12-09 DIPG-82. CLINICAL EXPERIENCE OF CONVECTION ENHANCED DELIVERY (CED) OF CARBOPLATIN AND SODIUM VALPROATE INTO THE PONS FOR THE TREATMENT OF DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG) IN CHILDREN AND YOUNG ADULTS AFTER RADIOTHERAPY Szychot, Elwira Walker, David Collins, Peter Hyare, Harpreet Shankar, Ananth Bienemann, Alison Hollingworth, Milo Gill, Steven Neuro Oncol Diffuse Midline Glioma/DIPG PURPOSE: Effective treatment of diffuse intrinsic pontine glioma (DIPG) remains a formidable challenge due to inadequate penetration of the blood-brain barrier (BBB) by systemically administered chemotherapies. The BBB can be overcome by directly infusing drugs into pons using method of convection-enhanced delivery (CED). We describe our clinical experience and what we have learned about the safety and feasibility of treating DIPG with intermittent CED of carboplatin and sodium valproate to the pons through the Renishaw Drug Delivery System (RDDS). METHODS: Retrospective review (2017–2020) of children with DIPG, who following radiotherapy, received compassionate treatment commencing 3.3–10 months post diagnosis (median 4.9 months). They received up to 7 cycles of 3–6 weekly pontine infusions of carboplatin (0.12-0.18mg/ml) and sodium valproate (14.4- 28.8mg/ml). RESULTS: 13 children 3–19 years (mean 6.9 years) were treated. There were no surgical complications. With the exception of infusion channels blocking in one device there were no adverse device effects. Two patients developed persistent 6(th) nerve palsies, which led to drug concentration reduction in the combination therapy. Subsequently infusion/ drug related toxicities were transient. Tumour was controlled in pons in 11/13 patients. Median progression free survival (PFS) was 13.0 months, while median overall survival (OS) was 15.3 months. CONCLUSIONS: Use of the RDDS was safe and well tolerated in all 13 patients. Treatment improved control of pontine disease resulting in longer PFS and OS than reported for conventional therapy and merits further evaluation in a clinical trial. Oxford University Press 2020-12-04 /pmc/articles/PMC7715416/ http://dx.doi.org/10.1093/neuonc/noaa222.123 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Diffuse Midline Glioma/DIPG
Szychot, Elwira
Walker, David
Collins, Peter
Hyare, Harpreet
Shankar, Ananth
Bienemann, Alison
Hollingworth, Milo
Gill, Steven
DIPG-82. CLINICAL EXPERIENCE OF CONVECTION ENHANCED DELIVERY (CED) OF CARBOPLATIN AND SODIUM VALPROATE INTO THE PONS FOR THE TREATMENT OF DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG) IN CHILDREN AND YOUNG ADULTS AFTER RADIOTHERAPY
title DIPG-82. CLINICAL EXPERIENCE OF CONVECTION ENHANCED DELIVERY (CED) OF CARBOPLATIN AND SODIUM VALPROATE INTO THE PONS FOR THE TREATMENT OF DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG) IN CHILDREN AND YOUNG ADULTS AFTER RADIOTHERAPY
title_full DIPG-82. CLINICAL EXPERIENCE OF CONVECTION ENHANCED DELIVERY (CED) OF CARBOPLATIN AND SODIUM VALPROATE INTO THE PONS FOR THE TREATMENT OF DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG) IN CHILDREN AND YOUNG ADULTS AFTER RADIOTHERAPY
title_fullStr DIPG-82. CLINICAL EXPERIENCE OF CONVECTION ENHANCED DELIVERY (CED) OF CARBOPLATIN AND SODIUM VALPROATE INTO THE PONS FOR THE TREATMENT OF DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG) IN CHILDREN AND YOUNG ADULTS AFTER RADIOTHERAPY
title_full_unstemmed DIPG-82. CLINICAL EXPERIENCE OF CONVECTION ENHANCED DELIVERY (CED) OF CARBOPLATIN AND SODIUM VALPROATE INTO THE PONS FOR THE TREATMENT OF DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG) IN CHILDREN AND YOUNG ADULTS AFTER RADIOTHERAPY
title_short DIPG-82. CLINICAL EXPERIENCE OF CONVECTION ENHANCED DELIVERY (CED) OF CARBOPLATIN AND SODIUM VALPROATE INTO THE PONS FOR THE TREATMENT OF DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG) IN CHILDREN AND YOUNG ADULTS AFTER RADIOTHERAPY
title_sort dipg-82. clinical experience of convection enhanced delivery (ced) of carboplatin and sodium valproate into the pons for the treatment of diffuse intrinsic pontine glioma (dipg) in children and young adults after radiotherapy
topic Diffuse Midline Glioma/DIPG
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7715416/
http://dx.doi.org/10.1093/neuonc/noaa222.123
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