Abstract
AVRO is an adjunctive four-drug regimen designed to increase the effectiveness of current standard treatment of glioblastoma (GB). AVRO is a repurposed drug regimen consisting of the antinausea drug aprepitant, the antidepressant vortioxetine, the emphysema treatment drug roflumilast, and the antipsychotic drug olanzapine. All four are EMA/FDA approved for nononcology indications, all four have strong research evidence showing inhibition of GB growth, and all four carry a low side effect risk. The goal of adding AVRO is to further retard GB growth, improving survival. Aprepitant is an antinausea drug that blocks NK-1 signaling, with a database of 59 studies showing growth inhibition in 22 different cancers, 12 of which were specific to GB. Fully 30 studies demonstrated that the SSRI class of antidepressants inhibited GB growth; accordingly, we chose one such agent, vortioxetine, to add to AVRO. Elevation of intracellular cAMP slowed GB growth in 21 independent studies. Accordingly, we added the emphysema treatment drug roflumilast, which inhibits cAMP degradation. Among the 27 currently marketed D2-blocking antipsychotic drugs, 24 have preclinical evidence of GB growth inhibition in a combined 84 independent study database. One of these 24 drugs is olanzapine, added to AVRO. Given the short median survival of GB as of mid-2025, the clinician and researcher community will benefit from wider awareness of the anti-GB effects of these four nononcology drugs.