Phase I/II study of bevacizumab with BKM120, an oral PI3K inhibitor, in patients with refractory solid tumors (phase I) and relapsed/refractory glioblastoma (phase II).

Background: Current bevacizumab-based regimens have failed to improve survival in patients with recurrent glioblastoma. To improve treatment efficacy, we evaluated bevacizumab + BKM120, an oral pan-class I PI3K inhibitor, in this patient population.

Methods: A brief phase I study established the optimal BKM120 dose to administer with standard-dose bevacizumab.

Glioblastoma cells incorporate into tumor vasculature and contribute to vascular radioresistance.

Glioblastoma multiforme (GBM) remains the most devastating neoplasm of the central nervous system and has a dismal prognosis. Ionizing radiation represents an effective therapy for GBM, but radiotherapy remains only palliative because of radioresistance. In this study, we demonstrate that glioma cells participate in tumor vascularization and contribute to vascular radioresistance.