title: Cardiovascular toxicity profiles of vascular-disrupting agents.
abstract: BACKGROUND
  Vascular-disrupting agents (VDAs) represent a new class of chemotherapeutic agent that targets the existing vasculature in solid tumors. Preclinical and early-phase trials have demonstrated the promising therapeutic benefits of VDAs but have also uncovered a distinctive toxicity profile highlighted by cardiovascular events.
  
  
  METHODS
  We reviewed all preclinical and prospective phase I-III clinical trials published up to August 2010 in MEDLINE and the American Association of Cancer Research and American Society of Clinical Oncology meeting abstracts of small-molecule VDAs, including combretastatin A4 phosphate (CA4P), combretastatin A1 phosphate (CA1P), MPC-6827, ZD6126, AVE8062, and ASA404.
  
  
  RESULTS
  Phase I and II studies of CA1P, ASA404, MPC-6827, and CA4P all reported cardiovascular toxicities, with the most common cardiac events being National Cancer Institute Common Toxicity Criteria (version 3) grade 1-3 hypertension, tachyarrhythmias and bradyarrhythmias, atrial fibrillation, and myocardial infarction. Cardiac events were dose-limiting toxicities in phase I trials with VDA monotherapy and combination therapy.
  
  
  CONCLUSIONS
  Early-phase trials of VDAs have revealed a cardiovascular toxicity profile similar to that of their vascular-targeting counterparts, the angiogenesis inhibitors. As these agents are added to the mainstream chemotherapeutic arsenal, careful identification of baseline cardiovascular risk factors would seem to be a prudent strategy. Close collaboration with cardiology colleagues for early indicators of serious cardiac adverse events will likely minimize toxicity while optimizing the therapeutic potential of VDAs and ultimately enhancing patient outcomes.
authors: Department of Internal Medicine, University of Texas Medical School at Houston, Houston, Texas, USA.
authors: Ishwaria M
authors: IM
authors: Subbiah
authors: Daniel J
authors: DJ
authors: Lenihan
authors: Apostolia M
authors: AM
authors: Tsimberidou
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D001632:Bibenzyls / Q000009:adverse effects / Q000627:therapeutic use; D002319:Cardiovascular System / Q000187:drug effects*; D002986:Clinical Trials as Topic; D006801:Humans; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D009943:Organophosphorus Compounds / Q000009:adverse effects / Q000627:therapeutic use; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use; D012694:Serine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D044004:Xanthones / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D020533:Angiogenesis Inhibitors; D001632:Bibenzyls; C455219:N-acetylcochinol-O-phosphate; D009943:Organophosphorus Compounds; D011799:Quinazolines; D044004:Xanthones; C066668:vadimezan; D012694:Serine; C040105:combretastatin; C400245:AC 7700; C522974:verubulin