Angiogenesis inhibition for glioblastoma at the edge: beyond AVAGlio and RTOG 0825.

摘要: The standard of care for patients with newly diagnosed glioblastoma was redefined in 2005 when the EORTC NCIC trial showed superiority concomitant and maintenance temozolomide (TMZ) radiotherapy over alone. Since then, numerous efforts have been made to build on this new regimen, mostly testing hypotheses that prolonged administration TMZ or inhibition angiogenesis will provide a survival benefit. most promising anti-angiogenesis agent, bevacizumab, is monoclonal antibody targets vascular endothelial growth factor (VEGF). Bevacizumab produced encouraging response rates progression-free data at 6-month landmark analyses. Other VEGF-targeting agents, such as cediranib VEGF trap, shown less convincing results their safety, tolerability, efficacy. Bevacizumab's conditional approval by FDA 2009 recurrent linked future demonstrations its efficacy prospective trials patients. Two were performed, largely parallel—one RTOG (RTOG-0825) United States, one Roche (AVAGlio), Europe.1 Rather mature from both presented 2013 American Society Clinical Oncology meeting Chicago.2,3 uniform picture: Progression-free significantly prolonged, quality life preserved AVAGlio trial, but not RTOG-0825. Overall improved, safety tolerability acceptable. subgroup analyses available so far do identify specific subgroups who particularly benefitted comparison suggests no major effect cross-over progression. As it stands, overall support routine use bevacizumab upfront treatment setting. This does exclude possibility molecular reveal beneficial glioblastoma. Another important question whether should remain disease because provides benefits. Answers other questions are also pending. Are we sure gain reflects true impact activity just altered imaging? If there modification biology, some tumors become more invasive malignant? Is maintaining early course worth paying price rapid clinical deterioration later on, possibly based induced refractoriness all further lines treatment? Answering latter deriving strategies prevent resistance escape appear be roads success adding inhibitors current paradigms