. Author manuscript; available in PMC: 2023 Jul 21.

Published in final edited form as: Nat Rev Neurol. 2022 Mar 11;18(4):221–236. doi: 10.1038/s41582-022-00621-0

Table 2 |.

Clinical trials in high-grade glioma: local delivery of chemotherapeutic agents

Study	Treatment	Study type	Patient cohort	Results	Adverse events (number of patients)
*Convection-enhanced delivery*
Saito et al. (2020)⁵⁷	Single dose of ACNU via convection-enhanced delivery	Phase I, dose-e scalation	Diffuse intrinsic pontine glioma or recurrent brainstem glioblastoma (n = 16)	Decrease in tumour volume in four of six patients at highest dose	Transient worsening of neurological deficits (11)
*Implanted and injected modalities*
Westphal et al. (2003)⁶⁰	Implanted biodegradable carmustine or placebo wafers after surgery, followed by radiotherapy	Phase III	Primary high-grade glioma or metastasis (n = 240)	Median OS (glioblastoma only), 13.5 months in carmustine group vs 11.4 months in controls; median PFS (glioblastoma only), 5.9 months in both groups	Increased occurrence of intracranial hypertension and cerebrospinal fluid leaks
De Bonis et al. (2012)⁶²	Carmustine wafers in resection cavity + temozolomide and radiotherapy vs temozolomide + radiotherapy only	Retrospective analysis	Primary or recurrent glioblastoma (n = 165)	Median OS (primary glioblastoma), 14 months in carmustine group vs 11 months in controls; median OS (recurrent glioblastoma), 8 months vs 9 months	Increased adverse events in patients who received eight wafers
Yang et al. (2018)⁶⁴	ACNU into resection cavity via Ommaya reservoir with transient BBB disruption vs standard chemoradiotherapy only	Phase II	Primary glioblastoma (n = 71)	Median OS, 18.5 months in ACNU group vs 16.0 months in controls; median PFS, 8.8 vs 7.0 months	No increase in adverse events
*Intra-arterial delivery*
Boockvar et al. (2011)⁶⁸	Single dose of intra-a rterial bevacizumab with osmotic BBB disruption	Phase I	Recurrent glioblastoma (n = 30)	Radiographic reduction in tumour size in most patients, most pronounced in patients who had not previously received bevacizumab (reduction in tumour enhancement on MRI, 34.7% vs 15.2% in previously treated group)	Seizures (2), peroperative rupture of right anterior cerebral artery causing subarachnoid haemorrhage and left hemiparesis (1)
Chakraborty et al. (2016)⁷¹	Single dose of intra-a rterial cetuximab with osmotic BBB disruption	Phase I	Recurrent glioblastoma (n = 15)	Well tolerated to 250 mg/m²	Anaphylaxis (1), seizure (1), cerebral oedema with seizure (1)
Fortin et al. (2014)⁷²	Repeated intracarotid carboplatin injection every 4 weeks	Phase II	Recurrent glioblastoma (n = 51)	3 complete responses, 22 partial responses, 14 with stable disease	Transient carotid spasms (3)

ACNU, nimustine hydrochloride; BBB, blood–brain barrier; OS, overall survival; PFS, progression-free survival.