title: Vascular and pharmacokinetic effects of EndoTAG-1 in patients with advanced cancer and liver metastasis.
abstract: BACKGROUND
  EndoTAG-1 (ET), a novel formulation of cationic liposomes carrying embedded paclitaxel (Taxol), shows antitumoral activity, targeting tumor endothelial cells in solid tumors. Patients with advanced metastatic cancer were evaluated investigating effects on pharmacokinetics and tumor vasculature using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and contrast-enhanced ultrasound (CEUS).
  
  
  METHODS
  The pharmacokinetic (PK) profile of ET (22 mg/m(2) i.v.) was evaluated after single and repeated doses. DCE-MRI and CEUS explored hepatic metastases before, during and after the 4-week treatment cycle. Angiogenic biomarkers were assessed. Tumor response was evaluated by modified RECIST.
  
  
  RESULTS
  The PK profile demonstrated slight accumulation of paclitaxel after repeated doses. DCE-MRI parameters K(trans) and/or iAUC(60) showed a trend to decrease. Changes of blood flow-dependent parameters of DCE-MRI and CEUS were well correlated. Angiogenic biomarkers revealed no clear trend. ET was generally well tolerated; common toxic effects were fatigue and hypersensitivity reactions. Nine (9 of 18) patients had stable disease after the first treatment cycle. Four patients without disease progression continued treatment.
  
  
  CONCLUSIONS
  This study including multiple pretreated patients with different metastatic cancer revealed individually distinctive hemodynamic alterations by DCE-MRI. The PK profiles of ET were similar as observed previously.
authors.affiliation: Magnetic Resonance Development and Application Center, Department of Radiology, University Medical Center Freiburg, Freiburg, Germany. ulrike.fasol@uniklinik-freiburg.de
authors.forename: U
authors.initials: U
authors.lastname: Fasol
authors.forename: A
authors.initials: A
authors.lastname: Frost
authors.forename: M
authors.initials: M
authors.lastname: Büchert
authors.forename: J
authors.initials: J
authors.lastname: Arends
authors.forename: U
authors.initials: U
authors.lastname: Fiedler
authors.forename: D
authors.initials: D
authors.lastname: Scharr
authors.forename: J
authors.initials: J
authors.lastname: Scheuenpflug
authors.forename: K
authors.initials: K
authors.lastname: Mross
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000804:Angiotensin II / Q000097:blood; D019540:Area Under Curve; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology*; D003287:Contrast Media; D019332:Endothelin-1 / Q000097:blood; D005260:Female; D006801:Humans; D007378:Interleukins / Q000097:blood; D008081:Liposomes; D008113:Liver Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000556:secondary*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000097:blood / Q000188:drug therapy / Q000473:pathology*; D014463:Ultrasonography; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D020533:Angiogenesis Inhibitors; D003287:Contrast Media; D019332:Endothelin-1; D007378:Interleukins; D008081:Liposomes; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000804:Angiotensin II; D017239:Paclitaxel