Phase I trial of convection-enhanced delivery of nimustine hydrochloride (ACNU) for brainstem recurrent glioma.
brainstem
convection-enhanced delivery
nimustine hydrochloride
recurrent glioma
temozolomide
Journal
Neuro-oncology advances
ISSN: 2632-2498
Titre abrégé: Neurooncol Adv
Pays: England
ID NLM: 101755003
Informations de publication
Date de publication:
Historique:
entrez:
10
7
2020
pubmed:
10
7
2020
medline:
10
7
2020
Statut:
epublish
Résumé
Treatment options for patients suffering brainstem gliomas are quite limited as surgery is not an option against intrinsic tumors at brainstem and chemotherapy generally failed to demonstrate its efficacy. Intracerebral convection-enhanced delivery (CED) is a novel approach for administering chemotherapy to patients with brain tumors. We present the results of phase I trial of CED of nimustine hydrochloride (ACNU), designed to determine the maximum tolerable concentration of ACNU, for patients with recurrent brainstem gliomas. Sixteen patients, aged 3-81 years old, suffering from recurrent brainstem gliomas, including diffuse intrinsic pontine glioma patients as well as patients with recurrent gliomas that originated from non-brainstem sites, were enrolled in this trial between February 2011 and April 2016. The dose/concentration escalation trial included 3 dose/concentration groups (0.25, 0.5, and 0.75 mg/mL, all at 7 mL) to determine the safety and tolerability of CED of ACNU. Real-time monitoring of drug distribution was performed by mixing gadolinium-tetraazacyclododecanetetraacetic acid (Gd-DOTA) in the infusion solution. CED of ACNU was given in combination with oral or intravenous temozolomide chemotherapy. CED of ACNU demonstrated antitumor activity, as assessed by radiographic changes and prolonged overall survival. The recommended dosage was 0.75 mg/mL. Drug-associated toxicity was minimal. Intracerebral CED of ACNU under real-time monitoring of drug distribution, in combination with systemic temozolomide, was well tolerated among patients with recurrent brainstem gliomas. The safety and efficacy observed suggest the clinical benefits of this strategy against this devastating disease. Based on this phase I study, further clinical development of ACNU is warranted.
Sections du résumé
BACKGROUND
BACKGROUND
Treatment options for patients suffering brainstem gliomas are quite limited as surgery is not an option against intrinsic tumors at brainstem and chemotherapy generally failed to demonstrate its efficacy. Intracerebral convection-enhanced delivery (CED) is a novel approach for administering chemotherapy to patients with brain tumors. We present the results of phase I trial of CED of nimustine hydrochloride (ACNU), designed to determine the maximum tolerable concentration of ACNU, for patients with recurrent brainstem gliomas.
METHODS
METHODS
Sixteen patients, aged 3-81 years old, suffering from recurrent brainstem gliomas, including diffuse intrinsic pontine glioma patients as well as patients with recurrent gliomas that originated from non-brainstem sites, were enrolled in this trial between February 2011 and April 2016. The dose/concentration escalation trial included 3 dose/concentration groups (0.25, 0.5, and 0.75 mg/mL, all at 7 mL) to determine the safety and tolerability of CED of ACNU. Real-time monitoring of drug distribution was performed by mixing gadolinium-tetraazacyclododecanetetraacetic acid (Gd-DOTA) in the infusion solution. CED of ACNU was given in combination with oral or intravenous temozolomide chemotherapy.
RESULTS
RESULTS
CED of ACNU demonstrated antitumor activity, as assessed by radiographic changes and prolonged overall survival. The recommended dosage was 0.75 mg/mL. Drug-associated toxicity was minimal.
CONCLUSIONS
CONCLUSIONS
Intracerebral CED of ACNU under real-time monitoring of drug distribution, in combination with systemic temozolomide, was well tolerated among patients with recurrent brainstem gliomas. The safety and efficacy observed suggest the clinical benefits of this strategy against this devastating disease. Based on this phase I study, further clinical development of ACNU is warranted.
Identifiants
pubmed: 32642691
doi: 10.1093/noajnl/vdaa033
pii: vdaa033
pmc: PMC7212853
doi:
Types de publication
Journal Article
Langues
eng
Pagination
vdaa033Informations de copyright
© The Author(s) 2020. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.
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