Benefit and risk of antiangiogenic drugs
47 slide(s) – 00:26:23– English –2010-09-27
Many pathways lead to angiogenesis in malignant gliomas. Up to date, the best known pathway that has been specifically targeted with drugs in the clinic is the VEGF pathway, which is over-expressed in up to 60%of glioblastomas and associated with a poor prognosis. Phase II trials from US groups have shown that bevacizumab, a monoclonal antibody to VEGF, alone or associated with irinotecan, is able to yield 35-60% of PR and CR, with PF6 of 43-50%. The impact on overall survival still remains to be defined. The greatest clinical benefit consists in a reduction of steroid requirement in up to 60% of patients. Most common adverse events are thromboembolic complications, hypertension, fatigue and rebound vasogenic oedema. Bleeding complications are relatively rare. Several phase III studies are ongoing to find the best regimen of combination (Vp-16, nitrosureas, molecular agents), timing and mode of evaluation of response. Two phase III trials in newly diagnosed GBMs are ongoing. Several other molecules, impacting different molecular targets implicated, in the development of new blood vessels are under investigation (cilengitide, sunitinib, sorafenib, cediranib, etc).