QOLP-23. PHASE II RANDOMISED PLACEBO-CONTROLLED DOUBLE-BLIND STUDY OF ACETAZOLAMIDE VERSUS PLACEBO FOR CEREBRAL OEDEMA IN RECURRENT AND/OR PROGRESSIVE HIGH-GRADE GLIOMA REQUIRING TREATMENT WITH DEXAMETHASONE

Agar, M; Nowak, A; Hovey, E; Barnes, E; Simes, J; Vardy, J; Wheeler, H; Leonard, R; Hall, M; Tim, E; Spyridopoulos, D; Sim, H-W; Lwin, Z; Dowling, A; Harrup, R; Jennens, R; Kichenadasse, G; Dunlop, T; Gzell, C; Koh, E-S

QOLP-23. PHASE II RANDOMISED PLACEBO-CONTROLLED DOUBLE-BLIND STUDY OF ACETAZOLAMIDE VERSUS PLACEBO FOR CEREBRAL OEDEMA IN RECURRENT AND/OR PROGRESSIVE HIGH-GRADE GLIOMA REQUIRING TREATMENT WITH DEXAMETHASONE

Nowak, A Hovey, E Barnes, E Simes, J Vardy, J Wheeler, H Leonard, R Hall, M Tim, E Spyridopoulos, D Sim, H-W Lwin, Z Dowling, A Harrup, R Jennens, R Kichenadasse, G Dunlop, T Gzell, C Koh, E-S

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Publisher:: Oxford University Press (OUP)
Publication Type:: Journal Article
Citation:: Neuro-Oncology, 2020, 22, (Supplement_2), pp. ii179-ii180
Issue Date:: 2020-11-09

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Field	Value	Language
dc.contributor.author	Agar, M https://orcid.org/0000-0002-6756-6119
dc.contributor.author	Nowak, A
dc.contributor.author	Hovey, E
dc.contributor.author	Barnes, E
dc.contributor.author	Simes, J
dc.contributor.author	Vardy, J
dc.contributor.author	Wheeler, H
dc.contributor.author	Leonard, R
dc.contributor.author	Hall, M
dc.contributor.author	Tim, E
dc.contributor.author	Spyridopoulos, D
dc.contributor.author	Sim, H-W
dc.contributor.author	Lwin, Z
dc.contributor.author	Dowling, A
dc.contributor.author	Harrup, R
dc.contributor.author	Jennens, R
dc.contributor.author	Kichenadasse, G
dc.contributor.author	Dunlop, T
dc.contributor.author	Gzell, C
dc.contributor.author	Koh, E-S
dc.date.accessioned	2021-04-27T05:59:14Z
dc.date.available	2021-04-27T05:59:14Z
dc.date.issued	2020-11-09
dc.identifier.citation	Neuro-Oncology, 2020, 22, (Supplement_2), pp. ii179-ii180
dc.identifier.issn	1522-8517
dc.identifier.issn	1523-5866
dc.identifier.uri	http://hdl.handle.net/10453/148429
dc.description.abstract	<jats:title>Abstract</jats:title> <jats:sec> <jats:title>INTRODUCTION</jats:title> <jats:p>Symptoms of raised intracranial pressure (ICP) in recurrent or progressive high-grade glioma (HGG) generally require corticosteroid treatment, often causing toxicity with variable effects on reversing ICP symptoms. Acetazolamide reduces ICP in other clinical settings including case series in glioma.</jats:p> </jats:sec> <jats:sec> <jats:title>AIM</jats:title> <jats:p>To explore whether addition of oral acetazolamide enables safe dexamethasone dose reduction in management of raised ICP in recurrent and/or progressive HGG.</jats:p> </jats:sec> <jats:sec> <jats:title>METHODS</jats:title> <jats:p>Participants had recurrent, progressive and/or persistent residual HGG requiring recommencement of dexamethasone, dose increase or dexamethasone dependency; prior/current bevacizumab was an exclusion. Eligible participants were randomised 1:1 to acetazolamide 250mg twice daily or placebo for 8 weeks. Standardised protocols were used for dexamethasone dose changes in both arms, with planned dose decrease from day 5 once ICP symptoms were stable. The primary endpoint was a composite of dexamethasone dose reduction and stability of performance status. Secondary endpoints included toxicity and feasibility (accrual and compliance).</jats:p> </jats:sec> <jats:sec> <jats:title>RESULTS</jats:title> <jats:p>Thirty participants of a planned sample of 84 were enrolled (mean age 58 y (32-89)) from 7 Australian sites. The mean baseline dexamethasone dose was 6.2mg (4-16mg). Mean duration on treatment was 38 days (4-57) in placebo group and 31 days (3-60) in acetazolamide group, with 9 participants (30%) completing all study treatment (6 placebo, 3 acetazolamide). Study withdrawal was due to adverse events (n=6 (1 placebo, 5 acetazolamide)) and disease progression (n=6 (3 per arm)). Four participants (13%) (2 per arm) were stable responders meeting the primary endpoint criteria (≥50% corticosteroid dose reduction from baseline by 28 days maintained for 7 days, and no deterioration in performance status). Ten participants experienced a total of 13 serious adverse events (acetazolamide arm: 5 participants (33%), 6 events, 2 related).</jats:p> </jats:sec> <jats:sec> <jats:title>DISCUSSION</jats:title> <jats:p>The addition of acetazolamide did not facilitate dexamethasone reduction. The study closed early due to poor accrual and increasing availability of bevacizumab.</jats:p> </jats:sec>
dc.language	en
dc.publisher	Oxford University Press (OUP)
dc.relation.ispartof	Neuro-Oncology
dc.relation.isbasedon	10.1093/neuonc/noaa215.748
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	1109 Neurosciences, 1112 Oncology and Carcinogenesis
dc.subject.classification	Oncology & Carcinogenesis
dc.title	QOLP-23. PHASE II RANDOMISED PLACEBO-CONTROLLED DOUBLE-BLIND STUDY OF ACETAZOLAMIDE VERSUS PLACEBO FOR CEREBRAL OEDEMA IN RECURRENT AND/OR PROGRESSIVE HIGH-GRADE GLIOMA REQUIRING TREATMENT WITH DEXAMETHASONE
dc.type	Journal Article
utslib.citation.volume	22
utslib.for	1109 Neurosciences
utslib.for	1112 Oncology and Carcinogenesis
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Health
pubs.organisational-group	/University of Technology Sydney/Faculty of Health/IMPACCT
utslib.copyright.status	closed_access	*
dc.date.updated	2021-04-27T05:59:12Z
pubs.issue	Supplement_2
pubs.publication-status	Published
pubs.volume	22
utslib.citation.issue	Supplement_2

Abstract:

Abstract INTRODUCTION Symptoms of raised intracranial pressure (ICP) in recurrent or progressive high-grade glioma (HGG) generally require corticosteroid treatment, often causing toxicity with variable effects on reversing ICP symptoms. Acetazolamide reduces ICP in other clinical settings including case series in glioma. AIM To explore whether addition of oral acetazolamide enables safe dexamethasone dose reduction in management of raised ICP in recurrent and/or progressive HGG. METHODS Participants had recurrent, progressive and/or persistent residual HGG requiring recommencement of dexamethasone, dose increase or dexamethasone dependency; prior/current bevacizumab was an exclusion. Eligible participants were randomised 1:1 to acetazolamide 250mg twice daily or placebo for 8 weeks. Standardised protocols were used for dexamethasone dose changes in both arms, with planned dose decrease from day 5 once ICP symptoms were stable. The primary endpoint was a composite of dexamethasone dose reduction and stability of performance status. Secondary endpoints included toxicity and feasibility (accrual and compliance). RESULTS Thirty participants of a planned sample of 84 were enrolled (mean age 58 y (32-89)) from 7 Australian sites. The mean baseline dexamethasone dose was 6.2mg (4-16mg). Mean duration on treatment was 38 days (4-57) in placebo group and 31 days (3-60) in acetazolamide group, with 9 participants (30%) completing all study treatment (6 placebo, 3 acetazolamide). Study withdrawal was due to adverse events (n=6 (1 placebo, 5 acetazolamide)) and disease progression (n=6 (3 per arm)). Four participants (13%) (2 per arm) were stable responders meeting the primary endpoint criteria (≥50% corticosteroid dose reduction from baseline by 28 days maintained for 7 days, and no deterioration in performance status). Ten participants experienced a total of 13 serious adverse events (acetazolamide arm: 5 participants (33%), 6 events, 2 related). DISCUSSION The addition of acetazolamide did not facilitate dexamethasone reduction. The study closed early due to poor accrual and increasing availability of bevacizumab.

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http://hdl.handle.net/10453/148429