Antiangiogenic Drugs in the Treatment of Advanced Epithelial Ovarian Cancer

Epithelial ovarian cancer (EOC) accounts for approximately 80-90% of all ovarian cancers, and 75% of the patients are diagnosed with advanced disease (stage III and IV). Front-line systemic chemotherapy improves survival in women with advanced EOC; however, tumor recurrence occurs in almost all advanced EOC patients at a median of 15 months from diagnosis, and 5-year survival is estimated at 10 to 30%. Additionally, around 20% of patients do not respond to standard front-line therapy. Tumoral angiogenesis plays an important role in the pathogenesis of EOC, and its inhibition might improve survival in patients with advanced EOC. High-grade EOC is characterized by overexpression of vascular endothelial growth factor (VEGF), which drives dysfunctional tumor-associated angiogenesis, contributing to high interstitial pressure and increased vascular permeability. Diverse anti-angiogenic drugs are under investigation, and direct targeting of this pathway can be achieved by sequestration of VEGF protein using monoclonal antibodies (bevacizumab) or engineered binding site molecules (aflibercept), blockade of the VEGF receptor-2 with monoclonal antibodies or inhibition of receptor associated tyrosine kinase with low molecular weight inhibitors (cediranib, pazopanib, sorafenib or BIBF-1120).