Background and Purpose Although bevacizumab (BV) has been approved as second-line

Background and Purpose Although bevacizumab (BV) has been approved as second-line therapy for recurrent glioblastoma (GB) the efficacy and safety of BV for patients with newly diagnosed GB remain unclear. 3.33 95 CI 2.73-4.06 p<0.00001) and 12 months (OR 2.10 95 CI 1.74-2.54 p<0.00001). There were no significant differences in median overall survival between the BV and ST groups (OR 1.01 95 0.83 P = 0.95). The BV group had higher survival rates at 6 months (OR 1.41 95 CI 1.09 P Carfilzomib = 0.01) and 12 months (OR 1.23 95 CI 1.02 P = 0.03) but a low survival rate at the 36-month follow-up (OR 0.57 95 CI 0.32 P = 0.04). For the incidence of adverse events three adverse outcomes were found to be significantly different between BV and ST groups including hypertension (8.37% vs. 1.62% p<0.000001) proteinuria (7.65% vs. 0% p<0.001) and fatigue (14.54% vs. 9.01% p = 0.05). Conclusions/Significance Our Carfilzomib study indicates that combination of BV with ST for newly diagnosed GB did not improve the median overall survival but result in longer median PFS maintaining the quality of life and functional status. However the long-term use of BV is associated with a higher incidence of adverse events and mortality. Study Registration This research was registered at PROSPERO. (Registration Number: CRD42016038247). Introduction Glioblastoma (GB) the most common primary malignant brain tumor in adults has a dismal prognosis with a median survival of 14 to 16 months [1]. Even with the best available standard therapies (surgical resection followed by radiotherapy and temozolomide) the prognosis of patients with GB remains low [2 3 When GB recurs the median overall survival is typically 3 to 9 months and available therapies have a limited impact on outcome [4]. Therefore development of new therapies is essential to improve the overall survival and prognosis of patients with newly diagnosed GB. During the past decade a large number of Carfilzomib targeted therapeutic agents have been developed and evaluated. GB is highly vascular and typically overexpresses vascular endothelial growth factor (VEGF) which promotes tumor angiogenesis contributing to tumor growth and progression [5-7]. Several clinical trials have suggested that VEGF could be a therapeutic target [8 9 The U.S. Food and Drug Administration (FDA) approved bevacizumab (BV) a humanized monoclonal antibody to VEGF for second-line treatment of recurrent GB [10 11 Despite its prolongation of progression-free survival (PFS) in patients with recurrent GB the impact of BV on overall survival remains undefined. Several clinical trials have reported that treatment with combinations of BV and other chemotherapeutic agents results in stable responses and a prolonged 6-month PFS rate in patients with recurrent high-grade Carfilzomib glioma but do not significantly prolong overall survival (OS) compared with previous trials [12-16]. Furthermore most of the complications caused by the toxicity of the combined chemotherapy led to discontinuation of treatment for patients with GB [17]. In 2009 2009 Zhang et al. conducted a meta-analysis to assess the efficacy and safety of BV alone compared with BV and irinotecan for recurrent GB [18]. The results indicated that the combination of BV and irinotecan may increase the rate of discontinuation and that there was no obvious improvement in overall survival in patients with recurrent GB. Furthermore this research included only nonrandomized control trials or small-sample retrospective studies. The data from low-quality research results in significant heterogeneity. From 2009 onward several randomized controlled trials (RCTs) were conducted to assess the effectiveness of BV for newly diagnosed GB [19-26]. Therefore it became necessary to Carfilzomib conduct a meta-analysis to assess the clinical efficacy of BV compared with standard therapy (ST) or other chemotherapies for newly diagnosed GB and Carfilzomib to evaluate the safety and adverse effects of these combinations. Materials and Methods There is no necessary for ethic approval in this meta-analysis which mainly based on the published studies. This Hsh155 study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement [27]. Literature Search and Study Selection Two reviewers (GY.L and MZ.H) performed the literature searching on the BV for patients with newly diagnosed GB to identify relevant articles published between January 1966 and August 2016. Electronic search used “bevacizumab” “avastin” “chemotherapy” “glioblastoma” “newly diagnosed glioblastoma” “GB” in Mesh and free terms. We searched PubMed EMBASE and the Cochrane Library to identify relevant studies. Manual searches.