title: Rationale for heating oxaliplatin for the intraperitoneal treatment of peritoneal carcinomatosis: a study of the effect of heat on intraperitoneal oxaliplatin using a murine model.
abstract: OBJECTIVE
  To study the effect of heat on the absorption of intraperitoneal (IP) oxaliplatin using a murine model.
  
  
  BACKGROUND
  Because of its efficiency in the systemic treatment of colorectal cancer, oxaliplatin is currently used in hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis. However, its properties when administered by the IP route have not been well characterized by preclinical studies.
  
  
  METHODS
  Under general anesthesia, 35 Sprague-Dawley rats were submitted to 3 different doses of IP oxaliplatin (460, 920, and 1840 mg/m(2)) at 3 different perfusion temperatures (37, 40, and 43°C) during 25 minutes. At the end of perfusion, samples in different compartments (peritoneum, portal blood, and systemic blood) were harvested and the concentrations of oxaliplatin were measured by high performance liquid chromatography.
  
  
  RESULTS
  As the dose of IP oxaliplatin was increased, higher concentrations were observed in every compartment. When the temperature of IP oxaliplatin was increased, it resulted in an increase of its peritoneal concentration (linear regression 0.38; 95% CI: 0.28-0.47) and in a decrease of its systemic blood (linear regression -1, 02; 95% CI: -1.45 to -0.60) and portal blood (linear regression -1.08; 95% CI: -1.70 to -0.47) concentrations.
  
  
  CONCLUSIONS
  Proportionally to the dose administered, IP oxaliplatin leads to high concentration of drug in peritoneal tissues. Furthermore, heat enhances peritoneal tissue concentration of Oxaliplatin while reducing its systemic absorption. This last effect may possibly lead to decreased systemic toxicity. These observations support the use of oxaliplatin for HIPEC.
authors.affiliation: Maisonneuve-Rosemont Research Center, Maisonneuve-Rosemont Hospital, University of Montreal, Montreal QC, Canada.
authors.forename: Nelson
authors.initials: N
authors.lastname: Piché
authors.forename: François A
authors.initials: FA
authors.lastname: Leblond
authors.forename: Lucas
authors.initials: L
authors.lastname: Sidéris
authors.forename: Vincent
authors.initials: V
authors.lastname: Pichette
authors.forename: Pierre
authors.initials: P
authors.lastname: Drolet
authors.forename: Louis-Philippe
authors.initials: LP
authors.lastname: Fortier
authors.forename: Andrew
authors.initials: A
authors.lastname: Mitchell
authors.forename: Pierre
authors.initials: P
authors.lastname: Dubé
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism*; D010478:Chemotherapy, Cancer, Regional Perfusion; D004195:Disease Models, Animal; D006358:Hot Temperature; D008297:Male; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000077150:Oxaliplatin; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin