Optimization of Intra-Arterial Administration of Chemotherapeutic Agents for Glioblastoma in the F98-Fischer Glioma-Bearing Rat Model.

Abstract

Glioblastoma (GBM) is a difficult disease to treat for different reasons, with the blood-brain barrier (BBB) preventing therapeutic drugs from reaching the tumor being one major hurdle. The median overall survival is only 14.6 months after the standard first line of treatment. At relapse, there is no recognized standard second-line treatment. Our team uses intra-arterial (IA) chemotherapy as a means to bypass the BBB, hence achieving an overall median survival of 25 months. However, most patients eventually fail the treatment and progress. This is why we wish to expand our portfolio of options in terms of chemotherapy agents available for IA administration. In this study, we tested topotecan, cytarabine, and new formulations of carboplatin and paclitaxel by IA administration in the F98-Fischer glioma-bearing rat model as a screening tool for identifying potential candidate drugs. The topotecan IA group showed increased survival compared to the intravenous (IV) group (29.0 vs. 23.5), whereas the IV cytarabine group survived longer than the IA group (26.5 vs. 22.5). The new formulation of carboplatin showed a significant increase in survival compared to two previous studies with the conventional form (37.5 vs. 26.0 and 30.0). As for paclitaxel, it was too neurotoxic for IA administration. Topotecan and the new formulation of carboplatin demonstrated significant results, warranting their transition for consideration in clinical trials.