Gliomas account for almost 80% of primary malignant brain tumors, and glioblastoma is the most common subtype. Despite treatment with surgery, radiation, and chemotherapy(Temozolomide) almost all patients with glioma experience recurrence and the median survival for most patients is less than 2 years. In recurrent disease, salvage therapies have been limited and result in minimal improvement in OS. This overwhelming need for improved treatments has driven the development of novel drugs that target glioma biology, specifically anti-VEGF therapies.~Malignant gliomas are considered among the most angiogenic of cancers and are mostly fueled by vascular endothelial growth factor (VEGF) signaling via its endothelial tyrosine kinase receptor VEGF receptor 2 (VEGFR2). Levels of VEGF and its receptor are correlated with the histologic grade of gliomas, with the highest levels present in glioblastoma.Thus glioblastoma has emerged as an attractive tumor in which to conduct clinical trials of novel anti-VEGF agents, such as monoclonal antibodies and tyrosine kinase inhibitors.~Bevacizumab is a recombinant humanized monoclonal antibody that binds all VEGF isoforms, causing reduced tumor vascularization and inhibiting tumor growth. In a single-institute, phase II trial of patients with recurrent high-grade glioma, bevacizumab in combination with irinotecan demonstrated 46% 6-month PFS and 57% OR rates. Following on from the results of this study, another phase II trial was conducted to evaluate the safety and efficacy of bevacizumab alone and in combination with irinotecan, again showing promising results. On the basis this study, as well as a study by Kreisl and colleagues, FDA has approved to bevacizumab for patients with recurrent glioblastoma in 2009. Despite bevacizumab therapy, 6-month progression-free survival (PFS) for relapsed or progressive high-grade gliomas is 30.8% to 50.3%, and median overall survival (OS) is less than 42 week. Thus, recurrent high-grade gliomas remains a largely unmet medical need, which highlights the need for novel and effective therapies.~Apatinib is a small-molecule tyrosine kinase inhibitor (TKI) that highly selectively binds to and strongly inhibits vascular endothelial growth factor receptor 2 (VEGFR-2). Apatinib has been demonstrated as monotherapy prolongs OS in patients with gastric or gastroesophageal junction adenocarcinoma after two or more lines of chemotherapy with moderate, reversible, and easily managed adverse events.~The study is aimed to evaluate the efficacy and safety of Apatinib and Irinotecan in patients with recurrent high-grade glioma.
The study is aimed to evaluate the efficacy and safety of Apatinib and Irinotecan in patients with recurrent high-grade glioma.