title: Treatment of experimental pancreatic cancer by doxorubicin-, mitoxantrone-, and irinotecan-drug eluting beads.
abstract: OBJECTIVE
  Peritoneal carcinomatosis is a common cause of death in pancreatic cancer patients. In this metastatic stage of the disease, few patients show a sustained response to therapy. In the palliative situation, targeted and compartment restricted delivery of drugs offers the opportunity to focus drugs directly to the tumor site, which is a prerequisite for avoiding toxic side effects. Here, we demonstrate the therapeutic efficiency of biocompatible polyvinyl-alcohol hydrogel drug eluting beads (DEBs) containing doxorubicin, mitoxantrone and irinotecan in vitro and in vivo in a syngenic model of experimental pancreatic cancer.
  
  
  METHODS
  Panc02 murine pancreatic carcinoma cells were exposed to doxorubicin, mitoxantrone and irinotecan DEBs and free compounds. The effect on cell proliferation and apoptosis induction was compared. Using this cell line, peritoneal carcinomatosis was induced in C57 black6 mice. Mortality, tumor load and therapy-associated weight loss were compared after treatment of tumor-bearing mice with DEBs or free compounds.
  
  
  RESULTS
  In vitro treatment with DEBs decreases tumor cell proliferation and induces apoptosis. The effect is less pronounced than with corresponding doses of the free drug. Repeated applications of the free drugs in vivo, however, induce significantly higher lethality and weight loss than corresponding doses of DEBs. No relevant differences in antitumoral activity were observed. Using computer tomography and HE-histology after subcutaneous and intraperitoneal injection of radiopaque beads no systemic spread of the beads could be found.
  
  
  CONCLUSIONS
  DEBs show the advantage of delivering potent cytotoxic activity to the intraperitoneal tumor manifestation while maintaining a low systemic toxicity.
authors: Surgical Clinic, University Medicine Mannheim, Mannheim, Germany.
authors: Vugar
authors: V
authors: Yagublu
authors: Natavan
authors: N
authors: Caliskan
authors: Andrew L
authors: AL
authors: Lewis
authors: Ralf
authors: R
authors: Jesenofsky
authors: Lala
authors: L
authors: Gasimova
authors: J-Matthias
authors: JM
authors: Löhr
authors: Michael
authors: M
authors: Keese
mesh_terms: D000818:Animals; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D005260:Female; D000077146:Irinotecan; D051379:Mice; D008810:Mice, Inbred C57BL; D008863:Microspheres; D008942:Mitoxantrone / Q000008:administration & dosage*; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D059004:Topoisomerase I Inhibitors / Q000008:administration & dosage
chemical_list: D059004:Topoisomerase I Inhibitors; D000077146:Irinotecan; D004317:Doxorubicin; D008942:Mitoxantrone; D002166:Camptothecin