A multi-institutional phase I study of acetazolamide with temozolomide in adults with newly diagnosed MGMT-methylated malignant glioma.

ABSTRACT:

Background

A significant unmet need exists for the treatment of glioblastoma, IDH-wildtype (GBM). Preclinical work shows that acetazolamide sensitizes GBM to temozolomide (TMZ) by overcoming TMZ resistance due to BCL-3-dependent upregulation of carbonic anhydrase. Acetazolamide is Food and Drug Administration-approved for the treatment of altitude sickness. Drug repurposing enables the application of drugs to diseases beyond initial indications. This multi-institutional, open-label, phase I trial examined a combination of acetazolamide and TMZ in patients with MGMT promoter-methylated high-grade glioma.

Methods

A total of 24 patients (GBM, IDH-wildtype = 22; Grade 4 astrocytoma, IDH-mutant = 1; Grade 3 astrocytoma, IDH-mutant = 1) were accr

SUBMITTER: Driscoll RK 

PROVIDER: S-EPMC10901541 | biostudies-literature | 2024 Jan-Dec

REPOSITORIES: biostudies-literature