title: Vascular disrupting agents:  a delicate balance between efficacy and side effects.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Service d'Innovations Thérapeutiques Précoces, Département de Médecine, Institut Gustave Roussy, Villejuif, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Hollebecque
authors.forename: Christophe
authors.initials: C
authors.lastname: Massard
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D008297:Male; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology; D065646:Thyroid Carcinoma, Anaplastic; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents