[Anti-angiogenic therapy for malignant glioma]

Glioblastoma(GBM)is the most malignant and frequent primary brain tumor. The current standard of care consists of maximum safe resection and radiotherapy with concomitant and subsequent temozolomide(TMZ)treatment. With this treatment plan, the prognosis of patients with GBM remains dismal, with a 5-year survival rate of<10%; thus development of effective, novel therapies is needed. Bevacizumab(Bev, Avastin®)is a humanized monoclonal antibody against vascular endothelial growth factor(VEGF), one of the major potent angiogenic factors for the growth of human cancers, including GBM. Bev has been shown to effectively shrink enhancing lesions of recurrent GBM and decrease symptom burden and brain edema. These positive results led to its approval for malignant glioma treatment in June 2013 in Japan. Two double-blind, placebo-controlled, randomized phase III studies of Bev in newly diagnosed GBM were conducted to verify its efficacy as a first-line therapy used in combination with TMZ. The results, which were reported at the American Society for Clinical Oncology(ASCO)meeting in June 2013, failed to show an increase in overall survival, despite prolongation in progression-free survival. These results led to many unsolved issues regarding the use of Bev for the treatment of GBM. We discuss these problems in this paper and highlight our institutional experience with Bev monotherapy for recurrent high-grade gliomas.