title: Intraperitoneal use of doxorubicin drug-eluting beads in sheep: a pilot safety study.
abstract: BACKGROUND
  Intraperitoneal carcinmatosis and intra-abdominal tumour cell dissemination may occur with several tumour entities. At this final stage of the tumour disease, systemic chemotherapy remains only palliative and may be accompanied by severe side-effects. Alternatively, compartment-based therapy by intraperitoneal (i.p.) instillation of doxorubicin drug-eluting beads (dox-DEB) has been proposed. Here we investigated the safety, pharmacokinetics and side-effects of i.p. dox-DEB in a large animal trial.
  
  
  METHODS
  Ten black-headed meat-sheep received i.p. polyvinyl-alcohol-encapsulated doxorubicin. The plasma concentration of doxorubicin, blood count and laboratory findings were recorded and histological examination of the organs was performed.
  
  
  RESULTS
  After i.p. instillation, elevated serum levels of doxorubicin were obtained. After this initial phase, serum levels remained constant. Upon autopsy, no signs of systemic toxicity were detected. Beads remained within the peritoneal cavity and were not systemically distributed. However, we found significant local toxicity in five sheep, three of which died due to severe peritonitis.
  
  
  CONCLUSIONS
  Doxorubicin can be successfully targeted to the peritoneal cavity by bead encapsulation. Local toxic effects must be controlled in order to facilitate clinical utility.
authors.affiliation: Clinic for Vascular and Endovascular Surgery, University Hospital Frankfurt, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Binder
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Lewis
authors.forename: Ralf
authors.initials: R
authors.lastname: Jesenofsky
authors.forename: Michael
authors.initials: M
authors.lastname: Neumaier
authors.forename: Evelyn
authors.initials: E
authors.lastname: Jäger
authors.forename: Philipp
authors.initials: P
authors.lastname: Ströbel
authors.forename: J-Matthias
authors.initials: JM
authors.lastname: Löhr
authors.forename: Michael
authors.initials: M
authors.lastname: Keese
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D002277:Carcinoma / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D008863:Microspheres; D010534:Peritoneal Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D010865:Pilot Projects; D012756:Sheep
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin