Antiangiogenic therapy for high-grade glioma

摘要: Background The most common primary brain tumours in adults are gliomas. Gliomas span a spectrum from low to high-grade and graded pathologically on scale of one four according the World Health Organization (WHO) classification. High-grade glioma (HGG) carries poor prognosis. Grade IV is known as glioblastoma (GBM) median survival treated patients about 15 months. GBMs rich blood vessels (i.e. highly vascular) protein vascular endothelial growth factor (VEGF), which promotes new vessel formation (the process angiogenesis). Antiangiogenic agents inhibit promote regression existing vessels. Several antiangiogenic have been investigated clinical trials newly diagnosed recurrent HGG, showing promising preliminary results. This review was undertaken report benefits harms associated with use treatment HGGs. Objectives To evaluate efficacy toxicity therapy glioma. intervention can be used two broad groups patients: those first diagnosis part 'adjuvant' therapy, or progressive disease. Comparisons will include following. • Treatment versus placebo. • (such chemotherapy chemoradiotherapy) added same without addition therapy. Search methods Searches were conducted identify published unpublished Randomised Controlled Trials (RCTs) starting 2000; following databases searched: Cochrane Central Register (CENTRAL), Issue 3, 2014; MEDLINE April 2014 EMBASE 2014. Proceedings relevant oncology conferences since 2000 handsearched. Selection criteria RCTs evaluating control HGG. Data collection analysis Review authors screened search results reviewed abstracts potentially articles before retrieving full text eligible articles. Main results After comprehensive literature search, seven RCTs identified (total 2987 participants). Significant design heterogeneity noted included studies, especially response assessment criteria used. All studies restricted GBMs, no evaluated other HGGs. Four available only abstract form. We reserved an overall quality evidence until final study publications received. The three that judged risk bias. participants this systematic did not show improvement OS (pooled hazard ratio (HR) 0.94, 95% confidence interval (CI) 0.86 1.02; P value 0.16). However, pooled analysis PFS six (2847 participants) showed (HR 0.74, CI 0.68 0.81; < 0.00001). Bevacizumab more likely yield favourable Pooled HR for bevacizumab (three 1712 significant at 0.66 (95% 0.59 0.74; 0.00001), reflected lower reported compared analysis. Nevertheless, finding 0.92, 0.83 0.12). Similar therapies solid tumours, adverse events related class hypertension proteinuria, wound healing potential thromboembolic events, although generally, occurrence grade 3 kind (< 14.1%), consistent findings tumours. Authors' conclusions In GBM, does improve survival, despite improved progression-free survival. Thus time, insufficient support GBM basis effects survival. Bevacizumab may confer benefit GBM; however favour using insufficient. Although appears prolong impact life remains unclear. Adequately powered, randomised, placebo-controlled (or HGG) needed. Not addressed here whether subsets these useful histologies.