title: Pharmacokinetic evaluation of vadimezan (ASA404, 5,6-dimethylxanthenone-4-acetic acid, DMXAA).
abstract: BACKGROUND
  Understanding the pharmacokinetics (PK) and pharmacodynamics of a drug is important to optimizing its use. Vadimezan is a tumor vascular-disrupting agent that acutely disrupts blood flow within tumors and induces innate tumor immunity. It has enhanced the activity of anticancer treatments in preclinical models and early phase trials, although one Phase III trial result was negative and another is yet to be reported.
  
  
  METHODS
  Areas covered in this review are the preclinical and human PK and the inter-relationship among PK, toxicity and efficacy of vadimezan as a single agent and in combination with other therapies. These data are derived from a literature search on Medline and also from conference proceedings, abstracts and trial reports available up to June 2011.
  
  
  CONCLUSIONS
  The disappointing results of one Phase III trial, despite the promising randomized Phase II trial data, highlight the challenges in translational research, especially in selecting the optimal development strategy. This paper discusses how different scheduling of vadimezan could significantly enhance the anticancer efficacy of this drug in combination with other therapies, especially those that do not require concurrent corticosteroid administration.
authors.affiliation: Waikato Hospital, Oncology Dept, Private Bag 3200, Pembroke St, Hamilton 3240, New Zealand. michael.jameson@waikatodhb.health.nz
authors.forename: Michael B
authors.initials: MB
authors.lastname: Jameson
authors.forename: Michelle
authors.initials: M
authors.lastname: Head
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics* / Q000494:pharmacology*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic; D044004:Xanthones / Q000493:pharmacokinetics* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D044004:Xanthones; C066668:vadimezan