title: Is the toxicity of anti-angiogenic drugs predictive of outcome? A review of hypertension and proteinuria as biomarkers of response to anti-angiogenic therapy.
abstract: BACKGROUND
  The prototypic anti-angiogenic agents, VEGF inhibitors, are increasingly used in clinical practice to treat a variety of tumours. Although generally well tolerated, their toxicities can be significant or occasionally life threatening. The ability to identify those patients whose disease will respond to VEGF inhibitors would minimise exposure to ineffective drugs for some patients. To date, there are no validated predictive or prognostic biomarkers for anti-angiogenic drugs. Toxicities such as hypertension and proteinuria are related to the effect of VEGF inhibition on the vasculature. This has led to the investigation of these toxicities as potential biomarkers of clinical outcome in patients treated with these agents.
  
  
  METHODS
  Putative mechanisms for the development of hypertension and proteinuria, and their potential role as clinically useful biomarkers in relation to anti-angiogenic drugs are discussed in this article. PUBMED, EMBASE and abstracts presented at the American Society of Clinical Oncology until July 2011 were searched to identify relevant English language articles. Studies of anti-angiogenic therapies testing the relationship of either hypertension or proteinuria with outcome were included.
  
  
  CONCLUSIONS
  The evidence in support of the hypothesis that hypertension and proteinuria are biomarkers of response to anti-angiogenic drugs is inconclusive. Current evidence suggests that hypertension is a pharmacodynamic effect of anti-angiogenic agents. Future studies should aim to measure and report toxicities in a standardised manner to facilitate comparisons between studies.
authors.affiliation: The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, UK. laura.horsley@manchester.ac.uk
authors.forename: Laura
authors.initials: L
authors.lastname: Horsley
authors.forename: Kalena
authors.initials: K
authors.lastname: Marti
authors.forename: Gordon C
authors.initials: GC
authors.lastname: Jayson
mesh_terms: D059250:Administration, Metronomic; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D023381:Endpoint Determination; D019317:Evidence-Based Medicine; D006801:Humans; D006973:Hypertension / Q000139:chemically induced*; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism; D018579:Patient Selection; D011507:Proteinuria / Q000139:chemically induced*; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D015415:Biomarkers; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A