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

in Biomolecules by Juliette Latulippe, Laurent-Olivier Roy, Fernand Gobeil, David Fortin

TLDR

  • A study tested new chemotherapy agents for intravenous and intra-arterial administration in a rat model of glioblastoma.
  • Topotecan and a new formulation of carboplatin showed promising results, demonstrating increased survival rates compared to standard treatments.
  • The study's findings support further research into the use of IA chemotherapy as a potential treatment option for glioblastoma.

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.

Overview

  • The study aimed to identify new chemotherapy agents for intra-arterial (IA) treatment of glioblastoma (GBM), bypassing the blood-brain barrier (BBB), to improve patient outcomes.
  • The study used the F98-Fischer glioma-bearing rat model to test topotecan, cytarabine, and new formulations of carboplatin and paclitaxel by IA administration.
  • The primary objective was to identify potential candidate drugs that could demonstrate improved survival rates compared to standard treatments.

Comparative Analysis & Findings

  • The topotecan IA group showed increased survival compared to the IV group (29.0 vs. 23.5), indicating the potential benefit of IA treatment.
  • The IV cytarabine group survived longer than the IA group (26.5 vs. 22.5), suggesting a potential advantage of IV treatment in certain cases.
  • The new formulation of carboplatin showed a significant increase in survival compared to previous studies with the conventional form (37.5 vs. 26.0 and 30.0), indicating its potential as a treatment option.

Implications and Future Directions

  • The study's findings suggest that topotecan and the new formulation of carboplatin warrant their transition for consideration in clinical trials to assess their efficacy in treating GBM.
  • Further research is needed to overcome the limitations of the study, such as the use of a rat model and the need for a larger sample size.
  • Exploring alternative treatment combinations and dosing regimens could help optimize the efficacy of IA chemotherapy in treating GBM.
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