THER-04. THE USE OF AN ADENOSINE A2 AGONIST TO IMPROVE THE PREVENTION AND TREATMENT OF BRAIN METASTASES

As systemic therapies for cancer become increasingly effective, there is generally a rise in the incidence of brain metastases as a site of first recurrence. This occurs because most antineoplastic agents do not reach the brain in therapeutic concentrations. Many approaches have been studied to improve drug distribution to the central nervous system (CNS) such as intra-arterial administration, osmotic blood-brain barrier (BBB) disruption, focused ultrasound, convection-enhanced delivery, development of CNS penetrant pro-drugs, and the use of vasoactive peptides to transiently disrupt the BBB. However, none of these has improved the prevention or treatment of CNS metastases. Regadenoson is an adenosine A2 agonist that is FDA approved for use in cardiac stress tests. In animals, it has been shown to transiently increase BBB permeability allowing high molecular weight dextran and chemotherapy to enter brain in higher concentrations. A clinical study designed to determine if regadenoson will perform similarly in humans has been CTEP approved and will soon be accruing patients through the Adult Brain Tumor Consortium. If the results are encouraging, future studies will focus on administering regadenoson concurrently with systemically administered chemotherapy in an effort to reduce the incidence of CNS metastases and to improve CNS drug delivery in patients with known brain metastases. This presentation will focus on the available pre-clinical and clinical data supporting this approach and the potential advantages and risks associated with transient BBB disruption in this setting.