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Drug | Target | Clinical phase | Results |
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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]. |
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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. |
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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]. |
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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]. |
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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]. |
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Marimastat | Broad-spectrum matrix metalloproteinase inhibitor | Phase III | Treatment with marimastat in SCLC and GBM patients does not improve survival [73, 74]. |
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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]. |
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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]. |
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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]. |
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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]. |
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