Phase II study of bevacizumab and temsirolimus combination therapy for recurrent glioblastoma multiforme

Bevacizumab combined with chemotherapy has recently shown promising efficacy in recurrent high-grade glioma. Phosphatase and tensin homolog (PTEN) mutation in glioblastoma multiforme (GBM) patients causes abnormally high activity of the pathways of Phosphatidylinositide 3-kinases (PI3K), Protein Kinase B (AKT), and the mammalian target of rapamycin (mTOR) and is associated with unfavorable prognosis. Temsirolimus, an mTOR inhibitor, has been well-tolerated in monotherapy, but with limited effects. The combination of temsirolimus and antibodies to vascular endothelial factor (VEGF) has not yet been investigated, but with the hypothesis that temsirolimus might provide complimentary therapeutic benefit in combination with bevacizumab, we included patients with progressive GBM after bevacizumab in an open phase II study.