title: An evidence-based review of the incidence of CNS bleeding with anti-VEGF therapy in non-small cell lung cancer patients with brain metastases.
abstract: BACKGROUND
  Vascular endothelial growth factor (VEGF) is a key mediator of angiogenesis. Solid tumors, including non-small cell lung cancer (NSCLC), are dependent on angiogenesis for growth and metastasis. Anti-VEGF therapy has demonstrated clinical benefits in the first-line treatment of NSCLC. Central nervous system (CNS) metastases are a common occurrence among patients with lung cancer and confer significant morbidity and mortality. The risk of CNS hemorrhage in NSCLC patients receiving anti-VEGF therapy is still relatively unexplored because patients with CNS metastases have generally been excluded from trials of anti-VEGF therapy due to a perceived increased risk of cerebral hemorrhage. Recently, large prospective, randomized trials, open-label studies and observational cohort studies in NSCLC have provided data on the incidence of CNS hemorrhage in large patient populations, reflective of community practice.
  
  
  METHODS
  We conducted a literature review for the available data on the incidence of CNS hemorrhage in NSCLC patients with brain metastases receiving anti-VEGF therapy.
  
  
  RESULTS
  There is no significantly increased risk of CNS hemorrhage in patients with NSCLC and emerging (previously untreated) or pretreated CNS metastases receiving anti-VEGF therapy.
  
  
  CONCLUSIONS
  We conclude that clinical trial data indicate that anti-VEGF therapy can be considered for NSCLC patients with emerging or pretreated CNS metastases.
authors.affiliation: Hematology/Oncology Division, Oregon Health Sciences University, Portland, OR 97239, USA. sandlera@ohsu.edu
authors.forename: Alan
authors.initials: A
authors.lastname: Sandler
authors.forename: Vera
authors.initials: V
authors.lastname: Hirsh
authors.forename: Martin
authors.initials: M
authors.lastname: Reck
authors.forename: Joachim
authors.initials: J
authors.lastname: von Pawel
authors.forename: Wallace
authors.initials: W
authors.lastname: Akerley
authors.forename: David H
authors.initials: DH
authors.lastname: Johnson
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000150:complications* / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D015994:Incidence; D020300:Intracranial Hemorrhages / Q000453:epidemiology* / Q000209:etiology*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D042461:Vascular Endothelial Growth Factor A