Table 2.

Examples of other promising Antiangiogenic agents in EOC.

	Mechanism of action	Current evidence
VEGF-mediated
Aflibercept (VEGF-Trap)	Soluble receptor which binds VEGF-A and-B as well as placenta-derived growth factor (PlGF) 1 and 2	Preliminary results reported by a Phase II trial conducted in recurrent setting showed similar results than bevacizumab, with a remarkable less incidence of bowel perforation (1%) [18]
		A phase III trial is ongoing
Cediranib	Small molecule that inhibits the tyrosine kinase domain of the VEFG receptor (VEGFR)	Two phase II trials in relapsing EOC demonstrated a response rate of nearly 20%, increasing up to 30% if disease stabilization is considered [19, 20]
	Other members of this family are sorafenib and sunitinib	ICON 6, a phase III trial in recurrent platinum-sensitive patients, is now testing this agent in combination with carboplatin and paclitaxel
Sorafenib	Multitargeted TKI that inhibits raf kinase, VEGFR-2, VEGFR-3, Flt-3, c-kit, and platelet-derived growth factor receptor (PDGFR)	Phase I trial reported that 50% of patients showed stable disease [21]. Early data from a subsequent phase II study testing the combination of sorafenib with gemcitabine in recurrent EOC confirmed encouraging activity, with an overall response rate of 33% [22]
		Several other phase II trials employing sorafenib either in front-line, maintenance phase, or recurrent settings, alone or in combination with standard chemotherapy or biologics (e.g., bevacizumab) are underway
		A randomized phase III trial is currently evaluating Sorafenib as a maintenance therapy after first-line treatment in EOC
Pazopanib	Oral tyrosine kinase inhibitor that targets VEGFR, PDGFR, and c-kit	Preliminary results of a phase II trial conducted in recurrent EOC defined by CA-125 elevation showed a biochemical response of 47%, with stable disease observed in other 27% [23]
		A phase III trial is currently evaluating pazopanib as a maintenance therapy after first-line treatment in EOC
Non VEGF-mediated
Vascular disrupting agents (VDAs)	Represent a new approach to deprive tumor from its blood supply, by causing the collapse of the established tumor vasculature. Their main targets are the endothelial cells	Preclinical data indicate that these drugs can improve tumor response to chemotherapy [24], radiation, and other Antiangiogenic therapies
	Examples include tubulin destabilizers and flavanoids, among others	Zweifel and coworkers presented recently the final results of a phase II trial employing Fosbretabulin (a tubulin binder) along with carboplatin and paclitaxel in platinum-resistant EOC, revealing a response rate of 32% [25]