Improving the Brain Delivery of Chemotherapeutic Drugs in Childhood Brain Tumors
The central nervous system (CNS) may be considered as a sanctuary site, protected from systemic chemotherapy by the meninges, the cerebrospinal fluid (CSF) and the blood-brain barrier (BBB). Consequently, parenchymal and CSF exposure of most antineoplastic agents following intravenous (IV) administr...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-06-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/11/6/824 |
| _version_ | 1797708310079602688 |
|---|---|
| author | Silvia Triarico Palma Maurizi Stefano Mastrangelo Giorgio Attinà Michele Antonio Capozza Antonio Ruggiero |
| author_facet | Silvia Triarico Palma Maurizi Stefano Mastrangelo Giorgio Attinà Michele Antonio Capozza Antonio Ruggiero |
| author_sort | Silvia Triarico |
| collection | DOAJ |
| description | The central nervous system (CNS) may be considered as a sanctuary site, protected from systemic chemotherapy by the meninges, the cerebrospinal fluid (CSF) and the blood-brain barrier (BBB). Consequently, parenchymal and CSF exposure of most antineoplastic agents following intravenous (IV) administration is lower than systemic exposure. In this review, we describe the different strategies developed to improve delivery of antineoplastic agents into the brain in primary and metastatic CNS tumors. We observed that several methods, such as BBB disruption (BBBD), intra-arterial (IA) and intracavitary chemotherapy, are not routinely used because of their invasiveness and potentially serious adverse effects. Conversely, intrathecal (IT) chemotherapy has been safely and widely practiced in the treatment of pediatric primary and metastatic tumors, replacing the neurotoxic cranial irradiation for the treatment of childhood lymphoma and acute lymphoblastic leukemia (ALL). IT chemotherapy may be achieved through lumbar puncture (LP) or across the Ommaya intraventricular reservoir, which are both described in this review. Additionally, we overviewed pharmacokinetics and toxic aspects of the main IT antineoplastic drugs employed for primary or metastatic childhood CNS tumors (such as methotrexate, cytosine arabinoside, hydrocortisone), with a concise focus on new and less used IT antineoplastic agents. |
| first_indexed | 2024-03-12T06:19:31Z |
| format | Article |
| id | doaj.art-30013705dc56437e899c89bd58146dab |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T06:19:31Z |
| publishDate | 2019-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-30013705dc56437e899c89bd58146dab2023-09-03T02:17:15ZengMDPI AGCancers2072-66942019-06-0111682410.3390/cancers11060824cancers11060824Improving the Brain Delivery of Chemotherapeutic Drugs in Childhood Brain TumorsSilvia Triarico0Palma Maurizi1Stefano Mastrangelo2Giorgio Attinà3Michele Antonio Capozza4Antonio Ruggiero5Pediatric Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Sacro Cuore, 00168 Rome, ItalyPediatric Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Sacro Cuore, 00168 Rome, ItalyPediatric Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Sacro Cuore, 00168 Rome, ItalyPediatric Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Sacro Cuore, 00168 Rome, ItalyPediatric Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Sacro Cuore, 00168 Rome, ItalyPediatric Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Sacro Cuore, 00168 Rome, ItalyThe central nervous system (CNS) may be considered as a sanctuary site, protected from systemic chemotherapy by the meninges, the cerebrospinal fluid (CSF) and the blood-brain barrier (BBB). Consequently, parenchymal and CSF exposure of most antineoplastic agents following intravenous (IV) administration is lower than systemic exposure. In this review, we describe the different strategies developed to improve delivery of antineoplastic agents into the brain in primary and metastatic CNS tumors. We observed that several methods, such as BBB disruption (BBBD), intra-arterial (IA) and intracavitary chemotherapy, are not routinely used because of their invasiveness and potentially serious adverse effects. Conversely, intrathecal (IT) chemotherapy has been safely and widely practiced in the treatment of pediatric primary and metastatic tumors, replacing the neurotoxic cranial irradiation for the treatment of childhood lymphoma and acute lymphoblastic leukemia (ALL). IT chemotherapy may be achieved through lumbar puncture (LP) or across the Ommaya intraventricular reservoir, which are both described in this review. Additionally, we overviewed pharmacokinetics and toxic aspects of the main IT antineoplastic drugs employed for primary or metastatic childhood CNS tumors (such as methotrexate, cytosine arabinoside, hydrocortisone), with a concise focus on new and less used IT antineoplastic agents.https://www.mdpi.com/2072-6694/11/6/824cerebrospinal fluid (CSF)blood-brain barrier (BBB)intrathecal (IT) chemotherapylumbar puncture (LP)Ommaya reservoirpersonalized medicine |
| spellingShingle | Silvia Triarico Palma Maurizi Stefano Mastrangelo Giorgio Attinà Michele Antonio Capozza Antonio Ruggiero Improving the Brain Delivery of Chemotherapeutic Drugs in Childhood Brain Tumors Cancers cerebrospinal fluid (CSF) blood-brain barrier (BBB) intrathecal (IT) chemotherapy lumbar puncture (LP) Ommaya reservoir personalized medicine |
| title | Improving the Brain Delivery of Chemotherapeutic Drugs in Childhood Brain Tumors |
| title_full | Improving the Brain Delivery of Chemotherapeutic Drugs in Childhood Brain Tumors |
| title_fullStr | Improving the Brain Delivery of Chemotherapeutic Drugs in Childhood Brain Tumors |
| title_full_unstemmed | Improving the Brain Delivery of Chemotherapeutic Drugs in Childhood Brain Tumors |
| title_short | Improving the Brain Delivery of Chemotherapeutic Drugs in Childhood Brain Tumors |
| title_sort | improving the brain delivery of chemotherapeutic drugs in childhood brain tumors |
| topic | cerebrospinal fluid (CSF) blood-brain barrier (BBB) intrathecal (IT) chemotherapy lumbar puncture (LP) Ommaya reservoir personalized medicine |
| url | https://www.mdpi.com/2072-6694/11/6/824 |
| work_keys_str_mv | AT silviatriarico improvingthebraindeliveryofchemotherapeuticdrugsinchildhoodbraintumors AT palmamaurizi improvingthebraindeliveryofchemotherapeuticdrugsinchildhoodbraintumors AT stefanomastrangelo improvingthebraindeliveryofchemotherapeuticdrugsinchildhoodbraintumors AT giorgioattina improvingthebraindeliveryofchemotherapeuticdrugsinchildhoodbraintumors AT micheleantoniocapozza improvingthebraindeliveryofchemotherapeuticdrugsinchildhoodbraintumors AT antonioruggiero improvingthebraindeliveryofchemotherapeuticdrugsinchildhoodbraintumors |