Dodecafluoropentane Emulsion as a Radiosensitizer in Glioblastoma Multiforme

Area of Science:

• Oncology
• Radiotherapy
• Pharmacology

Background:

• Glioblastoma multiforme (GBM) is a highly aggressive brain tumor characterized by significant hypoxia, contributing to its resistance to standard treatments like radiotherapy.
• Novel therapeutic strategies are needed to overcome treatment resistance and improve outcomes for GBM patients.

Purpose of the Study:

• To evaluate the safety and efficacy of dodecafluoropentane emulsion (DDFPe), a novel oxygen therapeutic, as an adjunct to chemoradiation in patients with GBM.
• To assess the impact of DDFPe on tumor hypoxia using TOLD MRI.

Main Methods:

• A multicenter, phase Ib/II dose-escalation study involving eleven GBM patients treated with DDFPe (0.05, 0.10, or 0.17 mL/kg) intravenously, supplemental oxygen, radiotherapy (2 Gy/fraction), and temozolomide (TMZ).
• Tumor response was monitored via serial MRI scans, and adverse events were recorded.
• Tissue oxygenation level-dependent (TOLD) contrast MRI was employed to measure changes in tumor hypoxia.

Main Results:

• DDFPe was generally well-tolerated when combined with radiotherapy and TMZ.
• Two patients experienced delayed grade 3 radiation necrosis at higher DDFPe doses, leading to the selection of 0.1 mL/kg for further evaluation.
• Median overall survival was 19.4 months and median progression-free survival was 9.6 months, comparing favorably to historical data.
• A statistically significant reduction in tumor T1 was observed in patients evaluable by TOLD MRI, indicating decreased hypoxia.

Conclusions:

• DDFPe is a generally safe radiosensitizer for GBM treatment and may offer a survival benefit.
• This study provides the first clinical evidence of hypoxia reversal in GBM using DDFPe and TOLD MRI.
• The recommended dose for phase II studies is 0.1 mL/kg of DDFPe.