Overview of anti-angiogenic agents in development for ovarian cancer

Objective. To review the rationale for targeting the vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF) pathways for anti-angiogenic therapy in patients with ovarian cancer and to summarize the currently available data with agents that block these pathways. Methods. Relevant papers and studies were identified by searches conducted on Medline using the terms angiogenesis, ovarian cancer, VEGF, PDGF, FGF, receptor, kinase, and inhibitor alone or in combination as well as by searches by drug name and by review of abstracts presented at recent oncology meetings. Results. The VEGF pathway is considered to be the key driver of angiogenesis, but the PDGF and FGF pathways also play important roles and may contribute to resistance to VEGF-specific blockade. Each pathway may also promote tumorigenesis; tumor cell overexpression of these growth factors and their receptors have been detected in ovarian tumor specimens, suggesting that autocrine loops may lead to tumor growth and progression. Selective inhibitors of the VEGF pathway (e.g., bevacizumab and VEGF Trap) as well as VEGF/PDGF pathway inhibitors (e.g., sorafenib and sunitinib) and VEGF/PDGF/FGF pathway inhibitors (e.g., cediranib, pazopanib, and BIBF 1120) have shown single-agent activity in women with ovarian cancer in phase II trials. Response rates of up to 21% have been reported with several agents in patients with recurrent ovarian cancer. Phase III trials with many anti-angiogenic agents in the treatment of ovarian cancer are currently ongoing. Conclusions. Anti-angiogenic agents may provide an improvement in the treatment of patients with recurrent ovarian cancer and may be useful when incorporated into first-line platinum/taxane therapy. It remains to be determined whether multitargeted agents will offer greater clinical benefit than specific VEGF pathway inhibitors. (C) 2010 Elsevier Inc. All rights reserved.