title: Pharmacokinetics of oxaliplatin during open versus laparoscopically assisted heated intraoperative intraperitoneal chemotherapy (HIPEC): an experimental study.
abstract: BACKGROUND
  Hyperthermic intraperitoneal chemotherapy (HIPEC) is being evaluated for patients with minimal residual or no residual disease after primary surgery and chemotherapy for stage III ovarian carcinoma. The technical feasibility of the laparoscopic approach for HIPEC has been demonstrated in a previous study. An experimental study on the porcine model was carried out to compare oxaliplatin pharmacokinetics during a laparoscopic-assisted procedure versus the coliseum technique for HIPEC.
  
  
  METHODS
  Adult pigs received an HIPEC procedure that was based on 460 mg/m(2) of oxaliplatin over 30 minutes with a perfusate heated at 41 degrees C to 43 degrees C. The HIPEC drains were placed in the upper and lower quadrants of the abdomen. Peritoneal fluid and blood samples were collected every 10 minutes during the procedure, and the pharmacokinetics of oxaliplatin was studied.
  
  
  RESULTS
  Two groups of 10 adult pigs were studied. All the procedures were successfully completed with an adequate intra-abdominal temperature and distribution. No major technical problems were encountered. At the end of the HIPEC, 41.5% of the molecule was absorbed in the laparoscopic group compared with 33.4% in the laparotomy group (P = .0543). Peritoneal oxaliplatin half-life (T((1/2))) was significantly faster in the laparoscopic procedure (median, 37.5 vs. 59.3 minutes, P = .02). The area under the curve ratio of peritoneal to plasma reflects a more important oxaliplatin crossing through the peritoneal barrier in the laparoscopic procedure (ratio, 16.4 in the closed procedure vs. 28.1 in the open one; P = .03).
  
  
  CONCLUSIONS
  This study confirms the technical feasibility and reliability of the laparoscopic approach for HIPEC, and it extends knowledge concerning peritoneal drug absorption. Oxaliplatin absorption is far higher with laparoscopy in terms of time course in peritoneal perfusion. Clinical application in selected patients may be expected after further experimental investigation designed to define the adequate drug dosage.
authors.affiliation: Department of Surgical Oncology, Institut Claudius Regaud, 20-24 Rue du Pont Pierre, 31052, Toulouse, Cedex, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: Gesson-Paute
authors.forename: Gwenael
authors.initials: G
authors.lastname: Ferron
authors.forename: Fabienne
authors.initials: F
authors.lastname: Thomas
authors.forename: Emanuelle Cohen
authors.initials: EC
authors.lastname: de Lara
authors.forename: Etienne
authors.initials: E
authors.lastname: Chatelut
authors.forename: Denis
authors.initials: D
authors.lastname: Querleu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D001202:Ascitic Fluid / Q000378:metabolism*; D005240:Feasibility Studies; D006979:Hyperthermia, Induced; D007263:Infusions, Parenteral; D010535:Laparoscopy; D009944:Organoplatinum Compounds / Q000493:pharmacokinetics*; D000077150:Oxaliplatin; D010529:Peritoneal Cavity; D013552:Swine; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin