CTNI-12. PHASE II MULTICENTRIC ITALIAN TRIAL ON REPOSITIONING OF THE ANTIPSYCHOTIC DRUG CHLORPROMAZINE AND ITS COMBINATION WITH TEMOZOLOMIDE IN MGMT UNMETHYLATED GLIOBLASTOMA PATIENTS: THE RACTAC TRIAL

Abstract The poor prognosis of patients affected by glioblastoma (GBM) prompts the search for new and more effective therapies, particularly GBMs with unmethylated MGMT. In this regard, drug repurposing, can represent a safe inexpensive way to bring novel pharmacological approaches from bench bedside. Chlorpromazine, medication in use since six decades therapy psychiatric disorders, shows vitro features that make it eligible repositioning GBM therapy. our experimentation on cell lines, chlorpromazine inhibited viability an apoptosis-independent way, induced polyploidy, reduced cloning efficiency as well neurosphere formation downregulated expression stemness genes. Notably, we found synergized temozolomide, reducing strongly cooperated inducing death all lines assayed. With these assumptions, started multicentric Phase II clinical trial newly diagnosed MGMT adding temozolomide adjuvant phase standard first-line therapeutic protocol. experimental procedure involves combination CPZ treatment TMZ Stupp is administered orally at dose 50 mg/day – GG 1-28 every cycle TMZ. At present, 53 out 60 planned have been enrolled, without relevant toxicity.