AUTHOR=Pace Andrea , Lombardi Giuseppe , Villani Veronica , Benincasa Dario , Abbruzzese Claudia , Cestonaro Ilaria , Corrà Martina , Padovan Marta , Cerretti Giulia , Caccese Mario , Silvani Antonio , Gaviani Paola , Giannarelli Diana , Ciliberto Gennaro , Paggi Marco G. 

TITLE=Efficacy and safety of chlorpromazine as an adjuvant therapy for glioblastoma in patients with unmethylated MGMT gene promoter: RACTAC, a phase II multicenter trial

JOURNAL=Frontiers in Oncology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1320710

DOI=10.3389/fonc.2023.1320710

ISSN=2234-943X

ABSTRACT=<sec><title>Introduction</title><p>Drug repurposing is a promising strategy to develop new treatments for glioblastoma. In this phase II clinical trial, we evaluated the addition of chlorpromazine to temozolomide in the adjuvant phase of the standard first-line therapeutic protocol in patients with unmethylated <italic>MGMT</italic> gene promoter.</p></sec><sec><title>Methods</title><p>This was a multicenter phase II single-arm clinical trial. The experimental procedure involved the combination of CPZ with standard treatment with TMZ in the adjuvant phase of the Stupp protocol in newly-diagnosed GBM patients carrying an unmethylated <italic>MGMT</italic> gene promoter. Progression-free survival was the primary endpoint. Secondary endpoints were overall survival and toxicity.</p></sec><sec><title>Results</title><p>Forty-one patients were evaluated. Twenty patients (48.7%) completed 6 cycles of treatment with TMZ+CPZ. At 6 months, 27 patients (65.8%) were without progression, achieving the primary endpoint. Median PFS was 8.0 months (95% CI: 7.0-9.0). Median OS was 15.0 months (95% CI: 13.1-16.9). Adverse events led to reduction or interruption of CPZ dosage in 4 patients (9.7%).</p></sec><sec><title>Discussion</title><p>The addition of CPZ to standard TMZ in the first-line treatment of GBM patients with unmethylated <italic>MGMT</italic> gene promoter was safe and led to a longer PFS than expected in this population of patients. These findings provide proof-of-concept for the potential of adding CPZ to standard TMZ treatment in GBM patients with unmethylated <italic>MGMT</italic> gene promoter.</p></sec><sec><title>Clinical trial registration</title><p><uri xlink:href="https://clinicaltrials.gov/study/NCT04224441" xmlns:xlink="http://www.w3.org/1999/xlink">https://clinicaltrials.gov/study/NCT04224441</uri>, identifier NCT04224441.</p></sec>