Vascular disrupting agents: a delicate balance between efficacy and side effects

Curr Opin Oncol. 2012 May;24(3):305-15. doi: 10.1097/CCO.0b013e32835249de.


Purpose of review: Targeting the tumor vasculature is an attractive approach for cancer therapy. Vascular disrupting agents (VDAs) are compounds that directly target tumor blood vessels and create central tumor necrosis. The current review aims to summarize the clinical development (i.e. safety and efficacy) of this class of compounds.

Recent findings: VDAs have demonstrated signs of clinical activity in different tumor types [e.g. anaplastic thyroid carcinoma (ATC), nonsmall cell lung carcinoma (NSCLC), ovarian cancer, sarcoma]. However, the lack of predictive biomarkers to identify patients with a high probability of response to VDAs, places this class of compounds at a high risk of failure. This has recently been exemplified by several negative phase II/III trials in NSCLC, ATC, and castration-refractory metastatic prostate cancer.

Summary: VDAs represent a unique class of anticancer compounds. Their clinical development is hampered by cardiovascular, neurological toxicities as single agent and by hematological toxicity in combination with chemotherapy. Molecular predictors of their efficacy are crucial for further development. As single agent, only few objective responses have been observed in a variety of solid tumors. However, VDAs have failed to demonstrate a survival advantage in several phase II/III trials especially in combination with chemotherapy.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / therapeutic use*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Clinical Trials as Topic
  • Female
  • Humans
  • Male
  • Neovascularization, Pathologic / drug therapy
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / pathology
  • Sarcoma / drug therapy*
  • Sarcoma / pathology
  • Thyroid Carcinoma, Anaplastic
  • Thyroid Neoplasms / drug therapy*
  • Thyroid Neoplasms / pathology
  • Treatment Outcome


  • Angiogenesis Inhibitors
  • Antineoplastic Agents