Antiangiogenic Therapy for Glioma

Table 2

Summary of the available treatments and the relative clinical phase and results.

Drug	Target	Clinical phase	Results
Endostatin (Endostar)	Interfere with the proangiogenic action of growth factors	Phase III 2005	Significant and clinical improvement in response rate, median time to tumor progression, and clinical benefit rate in combination with chemotherapy [67].
Bevacizumab (Avastin)	Monoclonal antibody anti-VEGF	Approved in 2004	In May 2009, the FDA approved Avastin as a single agent for the treatment of recurrent GBM based on the demonstration of objective response rates in two single-arm trials: AVF3708g and NCI 06-C-0064E.
Cilengitide	Selective inhibitor of αv integrins	Orphan drug by European medicines agency in 2008	Phase II trial in conjunction with chemotherapy and radiation: EMD 121974 in 2010 phase II trial in recurrent glioblastomas. The efficacy of the cilengitide alone is modest, but it is adequately delivered to the tumor [68]. In a phase II study, the addition of cilengitide to standard chemoradiotherapy demonstrated promising activity in GBM [69].
Etaracizumab (Abegrin)	Humanized monoclonal antibody direct against the human αvβ3 integrin	Phase II/phase I	Well tolerated with no evidence of immunogenicity [70]. Does not improve the effect of dacarbazine in a phase II trial of metastatic melanoma [71].
Volociximab	Chimeric monoclonal antibody that binds to and inhibits αvβ1 integrin	Phase II	Despite insufficient clinical activity in the refractory patient population to continue the study, weekly volociximab was well tolerated. A better understanding of the mechanism of action of volociximab will inform future development efforts [72].
Marimastat	Broad-spectrum matrix metalloproteinase inhibitor	Phase III	Treatment with marimastat in SCLC and GBM patients does not improve survival [73, 74].
Sorafenib	Small molecular inhibitor of several tyrosine protein kinases (VEGFR and PDGFR) and Raf kinases	Approved in 2007 for liver and kidney cancer	Phase I and II trials for brain tumors. Sorafenib can be safely administered [75, 76].
Cediranib	Potent inhibitor of VEGFR	Phase I, Phase II	Modest single-agent activity [77, 78]. Cediranib monotherapy yielded encouraging responses in recurrent glioblastoma in a phase II study [79].
Sunitinib	Multi-target receptor tyrosine kinase inhibitor	Approved for renal cell carcinoma and for imatinib-resistant gastrointestinal stromal tumor	Single-agent sunitinib exhibited insufficient activity in patients with recurrent glioblastoma in a phase II study [80].
Imatinib	Specific inhibitor of receptor tyrosine kinase	Approved in 2011 for ten different cancer types	In brain tumors, it did not show clinically meaningful antitumor activity in phase II and phase III trials [81–83].