Introduction: High-grade malignant brain tumors are the most common and most aggressive adult brain tumors with median overall survival durations of only 9-12 months for glioblastoma multiforme (GBM), and 3-4 years for anaplastic astrocytoma (AA). All patients experience a recurrence after first-line therapy, so improvements in both first-line and salvage therapy are critical to enhancing quality-of-life and prolonging survival. Carboplatin is an intravenous alkylating agent that is thought to work by interacting with DNA to inhibit DNA repair. Bevacizumab is an antiangiogenic monoclonal antibody targeting vascular endothelial growth factor. The aim of combining these two drugs is to harness the potential synergy of their antiangiogenic and cytotoxic properties. This phase I clinical research trial was designed to test the hypothesis that the combined administration of bevacizumab and carboplatin can be safely used by direct intracranial super-selective intra-arterial cerebral infusion (SIACI) to increase delivery to the brain and ultimately enhance survival of patients with primary GBM. We have previously shown that SIACI bevacizumab alone is safe in a phase I trial. By achieving the aims of this study we will determine the toxicity profile of SIACI bevacizumab and carboplatin.
Methods: Subjects with high-grade glioma were treated with mannitol followed by a single SIACI of bevacizumab and carboplatin. Bevacizumab was given at a fixed dose of 15 mg/kg. Carboplatin was given at a fixed dose of 150 mg/m2.
Results: Four patients have been treated. No treatment-induced adverse events pertaining to seizures, wound healing, bleeding, or blood counts were observed in this initial group within the first month of treatment. Patients continued to receive intravenous bevacizumab and carboplatin.
Conclusions: A combined infusion of bevacizumab and carboplatin can be safely tolerated through intra-arterial delivery at least up to a dose of 15 mg/kg of bevacizumab with 150 mg/m2 of carboplatin.
Patient Care: It will provide another alternative, safe treatment approach for patients with GBM. It will lead to subsequent phase II trials to observe the efficacy of intra-arterial bevacizumab and carboplatin as well as open the door for investigating other possible therapeutic combinations.
Learning Objectives: Intra-arterial infusion is a safe approach to deliver bevacizumab and carboplatin in GBM