Frontiers in Oncology (Dec 2023)

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

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

DOI
https://doi.org/10.3389/fonc.2023.1320710
Journal volume & issue
Vol. 13

Abstract

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IntroductionDrug 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 MGMT gene promoter.MethodsThis 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 MGMT gene promoter. Progression-free survival was the primary endpoint. Secondary endpoints were overall survival and toxicity.ResultsForty-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%).DiscussionThe addition of CPZ to standard TMZ in the first-line treatment of GBM patients with unmethylated MGMT 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 MGMT gene promoter.Clinical trial registrationhttps://clinicaltrials.gov/study/NCT04224441, identifier NCT04224441.

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