title: Comparison of hyperthermia and adrenaline to enhance the intratumoral accumulation of cisplatin in a murine model of peritoneal carcinomatosis.
abstract: BACKGROUND
  The best method to deliver intraperitoneal chemotherapy (IPC) for peritoneal carcinomatosis from ovarian cancer is not well defined. The aim of this study was to assess the ability of hyperthermia and adrenaline to enhance the intratumoral accumulation of cisplatin in a rat model of peritoneal carcinomatosis.
  
  
  METHODS
  Four groups of 5 BDIX rats with ovarian peritoneal carcinomatosis underwent IPC with 30 mg/l of cisplatin according to the following conditions: normothermia at 37° for 1 or 2 hours, hyperthermia at 42°C for 1 hour or normothermia at 37°C for 2 hours with 2 mg/l adrenaline. Tissue platinum content was measured by atomic absorption spectroscopy. The effect of hyperthermia, adrenaline and the duration of exposure to the drug was measured in vivo (tissue concentration of platinum in tumor, abdominal and extra abdominal tissues) and in vitro (cytotoxicity on human ovarian cancer cells).
  
  
  RESULTS
  In vitro, hyperthermia and longer exposure enhanced the accumulation and the cytotoxic effect of cisplatin on cancer cells. In vivo, only the 2 hours treatment with adrenaline resulted in increased platinum concentrations. The rats treated with adrenaline showed significantly lower concentrations of cisplatin in extra peritoneal tissues than those treated with hyperthermia.
  
  
  CONCLUSIONS
  Adrenaline is more effective than hyperthermia in order to enhance the intratumoral concentration of cisplatin in rats with peritoneal carcinomatosis from ovarian origin. It may also decrease the systemic absorption of the drug.
authors.affiliation: INSERM 866, Equipe Avenir, Dijon, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Facy
authors.forename: François
authors.initials: F
authors.lastname: Radais
authors.forename: Sylvain
authors.initials: S
authors.lastname: Ladoire
authors.forename: Delphine
authors.initials: D
authors.lastname: Delroeux
authors.forename: Hervé
authors.initials: H
authors.lastname: Tixier
authors.forename: François
authors.initials: F
authors.lastname: Ghiringhelli
authors.forename: Patrick
authors.initials: P
authors.lastname: Rat
authors.forename: Bruno
authors.initials: B
authors.lastname: Chauffert
authors.forename: Pablo
authors.initials: P
authors.lastname: Ortega-Deballon
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000378:metabolism* / Q000494:pharmacology; D004195:Disease Models, Animal; D004837:Epinephrine / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D010051:Ovarian Neoplasms / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000378:metabolism* / Q000556:secondary; D051381:Rats; D011919:Rats, Inbred Strains; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin; D004837:Epinephrine