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DDEL-14. SAFETY OF INTERVENTRICULAR METHOTREXATE ADMINISTRATION FOLLOWING RADIATION IN PEDIATRIC PATIENTS WITH MALIGNANT BRAIN TUMORS

BACKGROUND: Methotrexate has been used for intrathecal administration in leukemia as well as embryonal CNS tumors in children. Concerns about neurologic side effects including leukoencephalopathy, demyelination, and seizures have limited the use of methotrexate following exposure to focal radiation....

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Autores principales: Rosales, Kristofer, Maher, Ossama, Fader, Maggie, Gallegos, Natalie, Niazi, Toba, Ragheb, John, Khatib, Ziad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7715178/
http://dx.doi.org/10.1093/neuonc/noaa222.049
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author Rosales, Kristofer
Maher, Ossama
Fader, Maggie
Gallegos, Natalie
Niazi, Toba
Ragheb, John
Khatib, Ziad
author_facet Rosales, Kristofer
Maher, Ossama
Fader, Maggie
Gallegos, Natalie
Niazi, Toba
Ragheb, John
Khatib, Ziad
author_sort Rosales, Kristofer
collection PubMed
description BACKGROUND: Methotrexate has been used for intrathecal administration in leukemia as well as embryonal CNS tumors in children. Concerns about neurologic side effects including leukoencephalopathy, demyelination, and seizures have limited the use of methotrexate following exposure to focal radiation. OBJECTIVE: To evaluate and determine safety of Intraventricular administration of Methotrexate in pediatric patients with recurrent malignant brain tumors along with systemic Topotecan and Cyclophosphamide after exposure to prior radiation therapy. DESIGN/METHOD: Patients with recurrent cerebellar embryonal tumors after standard treatment that included radiation were enrolled on this IRB approved phase 2 study. An Ommaya reservoir was inserted in the lateral ventricle and used to administer 4 daily doses of methotrexate (2 mg/dose) along with (Topotecan [0.75mg/m2/day] and Cyclophosphamide [250 mg/m2/day]). A neurological evaluation was performed at baseline and daily during the intraventricular administration of the Methotrexate, this evaluation was repeated prior to each subsequent cycle and at completion of the protocol. RESULTS: Three patients (age range 3–20) received 2–3 cycles of intra-Ommaya Methotrexate and Topotecan/Cyclophosphamide. No MRI demyelination or white matter changes were seen after completion of the intraventricular Methotrexate therapy. None of the patients enrolled on this trial had adverse effects related to the therapy regimen received. Clinical neurological status was unchanged during the entire course of the treatment and upon completion of the scheduled therapy. CONCLUSION: Intraventricular administration of daily low dose Methotrexate is well tolerated in children with recurrent embryonal CNS tumors who had prior exposure to radiation.
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spelling pubmed-77151782020-12-09 DDEL-14. SAFETY OF INTERVENTRICULAR METHOTREXATE ADMINISTRATION FOLLOWING RADIATION IN PEDIATRIC PATIENTS WITH MALIGNANT BRAIN TUMORS Rosales, Kristofer Maher, Ossama Fader, Maggie Gallegos, Natalie Niazi, Toba Ragheb, John Khatib, Ziad Neuro Oncol Drug Delivery/Pharmacokinetics BACKGROUND: Methotrexate has been used for intrathecal administration in leukemia as well as embryonal CNS tumors in children. Concerns about neurologic side effects including leukoencephalopathy, demyelination, and seizures have limited the use of methotrexate following exposure to focal radiation. OBJECTIVE: To evaluate and determine safety of Intraventricular administration of Methotrexate in pediatric patients with recurrent malignant brain tumors along with systemic Topotecan and Cyclophosphamide after exposure to prior radiation therapy. DESIGN/METHOD: Patients with recurrent cerebellar embryonal tumors after standard treatment that included radiation were enrolled on this IRB approved phase 2 study. An Ommaya reservoir was inserted in the lateral ventricle and used to administer 4 daily doses of methotrexate (2 mg/dose) along with (Topotecan [0.75mg/m2/day] and Cyclophosphamide [250 mg/m2/day]). A neurological evaluation was performed at baseline and daily during the intraventricular administration of the Methotrexate, this evaluation was repeated prior to each subsequent cycle and at completion of the protocol. RESULTS: Three patients (age range 3–20) received 2–3 cycles of intra-Ommaya Methotrexate and Topotecan/Cyclophosphamide. No MRI demyelination or white matter changes were seen after completion of the intraventricular Methotrexate therapy. None of the patients enrolled on this trial had adverse effects related to the therapy regimen received. Clinical neurological status was unchanged during the entire course of the treatment and upon completion of the scheduled therapy. CONCLUSION: Intraventricular administration of daily low dose Methotrexate is well tolerated in children with recurrent embryonal CNS tumors who had prior exposure to radiation. Oxford University Press 2020-12-04 /pmc/articles/PMC7715178/ http://dx.doi.org/10.1093/neuonc/noaa222.049 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 Drug Delivery/Pharmacokinetics
Rosales, Kristofer
Maher, Ossama
Fader, Maggie
Gallegos, Natalie
Niazi, Toba
Ragheb, John
Khatib, Ziad
DDEL-14. SAFETY OF INTERVENTRICULAR METHOTREXATE ADMINISTRATION FOLLOWING RADIATION IN PEDIATRIC PATIENTS WITH MALIGNANT BRAIN TUMORS
title DDEL-14. SAFETY OF INTERVENTRICULAR METHOTREXATE ADMINISTRATION FOLLOWING RADIATION IN PEDIATRIC PATIENTS WITH MALIGNANT BRAIN TUMORS
title_full DDEL-14. SAFETY OF INTERVENTRICULAR METHOTREXATE ADMINISTRATION FOLLOWING RADIATION IN PEDIATRIC PATIENTS WITH MALIGNANT BRAIN TUMORS
title_fullStr DDEL-14. SAFETY OF INTERVENTRICULAR METHOTREXATE ADMINISTRATION FOLLOWING RADIATION IN PEDIATRIC PATIENTS WITH MALIGNANT BRAIN TUMORS
title_full_unstemmed DDEL-14. SAFETY OF INTERVENTRICULAR METHOTREXATE ADMINISTRATION FOLLOWING RADIATION IN PEDIATRIC PATIENTS WITH MALIGNANT BRAIN TUMORS
title_short DDEL-14. SAFETY OF INTERVENTRICULAR METHOTREXATE ADMINISTRATION FOLLOWING RADIATION IN PEDIATRIC PATIENTS WITH MALIGNANT BRAIN TUMORS
title_sort ddel-14. safety of interventricular methotrexate administration following radiation in pediatric patients with malignant brain tumors
topic Drug Delivery/Pharmacokinetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7715178/
http://dx.doi.org/10.1093/neuonc/noaa222.049
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