In recent years, angiogenesis inhibitors targeted VEGF signal pathways have become a focus for the management of recurrent GBM, and bevacizumab has been approved for use as single agent in these patients[37, 38]. the main outcomes of interest between bevacizumab and additional angiogenesis inhibitors. All analyses were performed using Comprehensive Meta Analysis software (Version 2.0). Results A total of 842 individuals were included for analysis: 343 individuals were treated with bevacizumab, 386 with additional angiogenesis inhibitors and 81 with thalidomide. The pooled ORR, 6-weeks PFS, and 1-yr OS for recurrent GBM individuals receiving angiogenesis inhibitors was 20.1%, 19.5% and 29.3%, respectively. The use of solitary agent bevacizumab in recurrent GBM significantly improved ORR and 6-weeks PFS when compared to additional angiogenesis inhibitors [relative risk (RR) 2.93, 95% CI 1.38C6.21; = 0.025; and RR 2.36 95% CI 1.46C3.82; = 0.07). when compared to thalidomide, bevacizumab treatment in recurrent GBM significantly improved ORR (RR 6.8, 95%CI: 2.64C17.6, p 0.001), but not for 6-weeks PFS (= 0.07) and 1-yr OS (= 0.31). As for grade 3/4 toxicities, the common toxicity was hypertension with pooled incidence of 12.1%, while high-grade thromboembolic events (2.2%), hemorrhage (5.1%) and GI perforation (2.8%) associated with angiogenesis inhibitors were relatively low. Conclusions In comparison with additional angiogenesis inhibitors and thalidomide, the use of solitary agent bevacizumab as salvage treatment for recurrent GBM individuals improve ORR and 6-weeks PFS, but not for 1-yr OS. Intro Glioblastoma multiforme (GBM) is the most common malignant main mind tumor in adults, with an average incidence rate of more than 3/100,000 individuals each year [1, 2]. The current standard of care is definitely maximal safe medical resection followed by adjuvant concomitant chemoradiotherapy and subsequent consolidation chemotherapy, generally with temozolomide [3, 4]. Despite BM212 this multimodality treatment approach, nearly all individuals encounter disease progression. And the prognosis of recurrent GBM remains dismal, having a median survival of only 14 to 16 weeks, with 5-yr overall survival rate less than 10% [5C7]. For individuals with recurrent GBM, salvage chemotherapeutic or biological agents are the most common approach for second-line treatment as most of these individuals will not be candidates for new surgery treatment or re-irradiation. Earlier study offers found that GBM is definitely a highly vascularized tumor in which micro-vascular proliferation is typically observed [8C10], Rabbit Polyclonal to PPGB (Cleaved-Arg326) and vascular endothelial growth factor (VEGF) has been identified as a prominent mediator of tumor angiogenesis [11, 12]. Therefore, angiogenesis inhibitors focusing on the VEGF transmission pathway obtain a focus of significant medical interest. Bevacizumab, a humanized antibody to VEGF, received BM212 accelerated US Food and Drug Administration (FDA) authorization in May 2009 for use as a single agent in individuals with GBM who have progressive disease following front-line therapy consisting of medical resection, radiotherapy, and temozolomide[4, 13, 14]. In an attempt to improve treatment results, several novel angiogenesis inhibitors have been investigated in prospective clinical tests. However, to our best knowledge, no systematic review focusing on the effectiveness and toxicities associated with angiogenesis inhibitors only in recurrent GBM has been performed, and whether bevacizumab is definitely more efficient than additional angiogenesis inhibitors and thalidomide remains BM212 unfamiliar. Therefore, we perform a systematic review and meta-analysis of published BM212 data to compared treatment results with solitary agent bevacizumab versus additional angiogenesis inhibitors and thalidomide for recurrent GBM individuals. Method and Materials Search strategy and selection of tests We Performed this meta-analysis adheres to the Preferred Reporting Items for Systematic Evaluations and Meta-Analyses (PRISMA) statements[15] (S1 table). To identify studies for inclusion in our systematic evaluate and meta-analysis, we did a broad search of four databases, including Embase, Medline, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Evaluations, from your date of BM212 inception of every database to July 2015. The complete search strategy used has been offered (S1 Text). No language restrictions were applied. To be eligible for inclusion in our systematic evaluate and meta-analysis, study populations (referred to hereafter as cohorts) experienced to meet all the following criteria: 1) individuals with recurrent glioblastoma refractory to earlier treatments; 2) treatment with angiogenesis inhibitors alone; 3) reported results of interest (ie, objective response rate, 6-weeks PFS and 1-yr OS; and 4) from an original prospective study (ie, randomized controlled trial and non-randomized medical trial). Data extraction Two investigators screened the titles and abstracts of potentially relevant studies. We retrieved the full.