Objectives Symptoms of raised intracranial pressure (ICP) in recurrent high-grade glioma (HGG) generally require corticosteroid treatment, often causing toxicity with variable effects on ICP symptoms. Acetazolamide reduces ICP when used in other clinical non-cancer settings. The aim of the study was to explore whether the addition of oral acetazolamide enables safe dexamethasone dose reduction in management of raised ICP in recurrent HGG.
Methods Participants had recurrent HGG with any of dexamethasone recommencement, dose increase or dependency; prior/current bevacizumab was an exclusion. Eligible participants were randomised 1:1 to acetazolamide or placebo for 8 weeks. Standardised protocols were used for dexamethasone dosing, with planned dose decrease from day 5 once ICP symptoms were stable. The primary endpoint was a composite of dexamethasone dose reduction and stable Karnofsky Performance Status Secondary endpoints included toxicity and feasibility.
Results Thirty participants (15 per group) were enrolled (mean age 58 years) from seven Australian sites. The mean baseline dexamethasone dose was 6.2 mg. Mean duration on study treatment was 38 days (placebo group) and 31 days (acetazolamide group) with nine participants (30%) completing all study treatments (six placebo, three acetazolamide). Study withdrawal was due to adverse events (n=6; one placebo, five acetazolamide) and disease progression (n=6 (three per arm)). Four participants (13%) (two per arm) were stable responders. Ten participants experienced a total of 13 serious adverse events (acetazolamide arm: five participants (33%), six events, two related).
Conclusions The study closed early due to poor accrual and increasing availability of bevacizumab. The addition of acetazolamide did not facilitate dexamethasone reduction.
Trial registration number ACTRN12615001072505.
- supportive care
- quality of life
Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information.
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Contributors MA, EHB, ES-K wrote the main manuscript text. AN, EJH, JS, JLV, HRW, H-WS, ZL, AD, RH, RJ, GK, TD, CG and E-SK collected data. EHB prepared all tables and figures. All authors reviewed the manuscript. ESK is responsible for the overall content as guarantor, had full access to the data and controlled the decision to publish.
Funding Cancer Australia Priority-Driven Collaborative Cancer Research Scheme (APP1098932); Perpetual Foundation (FR2014_0337).
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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