title: Vascular disrupting agent for neovascular age related macular degeneration: a pilot study of the safety and efficacy of intravenous combretastatin A-4 phosphate.
abstract: BACKGROUND
  This study was designed to assess the safety, tolerability, and efficacy of intravenous infusion of CA4P in patients with neovascular age-related macular degeneration (AMD).
  
  
  METHODS
  Prospective, interventional, dose-escalation clinical trial. Eight patients with neovascular AMD refractory to at least 2 sessions of photodynamic therapy received CA4P at a dose of 27 or 36 mg/m2 as weekly intravenous infusion for 4 consecutive weeks. Safety was monitored by vital signs, ocular and physical examinations, electrocardiogram, routine laboratory tests, and collection of adverse events. Efficacy was assessed using retinal fluorescein angiography, optical coherence tomography, and best corrected visual acuity (BCVA).
  
  
  RESULTS
  The most common adverse events were elevated blood pressure (46.7%), QTc prolongation (23.3%), elevated temperature (13.3%), and headache (10%), followed by nausea and eye injection (6.7%). There were no adverse events that were considered severe in intensity and none resulted in discontinuation of treatment. There was reduction of the excess foveal thickness by 24.15% at end of treatment period and by 43.75% at end of the two-month follow-up (p = 0.674 and 0.161, respectively). BCVA remained stable throughout the treatment and follow-up periods.
  
  
  CONCLUSIONS
  The safety profile of intravenous CA4P was consistent with that reported in oncology trials of CA4P and with the class effects of vascular disruptive agents; however, the frequency of adverse events was different. There are evidences to suggest potential efficacy of CA4P in neovascular AMD. However, the level of systemic safety and efficacy indicates that systemic CA4P may not be suitable as an alternative monotherapy to current standard-of-care therapy.
authors: Wilmer Eye Institute, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA.
authors: Mohamed A
authors: MA
authors: Ibrahim
authors: Diana V
authors: DV
authors: Do
authors: Yasir J
authors: YJ
authors: Sepah
authors: Syed M
authors: SM
authors: Shah
authors: Elizabeth
authors: E
authors: Van Anden
authors: Gulnar
authors: G
authors: Hafiz
authors: J Kevin
authors: JK
authors: Donahue
authors: Richard
authors: R
authors: Rivers
authors: Jai
authors: J
authors: Balkissoon
authors: James T
authors: JT
authors: Handa
authors: Peter A
authors: PA
authors: Campochiaro
authors: Quan Dong
authors: QD
authors: Nguyen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D005260:Female; D005334:Fever / Q000139:chemically induced; D006261:Headache / Q000139:chemically induced; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D007262:Infusions, Intravenous; D008133:Long QT Syndrome / Q000139:chemically induced; D008268:Macular Degeneration / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D013267:Stilbenes / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D013267:Stilbenes; C058728:fosbretabulin