title: Heated intra-operative intraperitoneal oxaliplatin plus irinotecan after complete resection of peritoneal carcinomatosis: pharmacokinetics, tissue distribution and tolerance.
abstract: BACKGROUND
  The purpose of this study was to report the pharmacokinetics (PK) and tolerance profile of intraoperative intraperitoneal chemo-hyperthermia (IPCH) with oxaliplatin and irinotecan.
  
  
  METHODS
  Thirty-nine patients with peritoneal carcinomatosis (PC) of either gastrointestinal or peritoneal origin underwent complete cytoreductive surgery followed by IPCH with a stable dose of oxaliplatin (460 mg/m(2)), plus one among seven escalating doses of irinotecan (from 300 to 700 mg/m(2)). IPCH was carried out with the abdomen open, for 30 min at 43 degrees C, with 2 l/m(2) of a 5% dextrose instillation in a closed continuous circuit. Patients received intravenous leucovorin (20 mg/m(2)) and 5-fluorouracil (400 mg/m(2)) just before IPCH to maximize the effect of oxaliplatin and irinotecan.
  
  
  RESULTS
  Irinotecan concentration in tumoral tissue increased until 400 mg/m(2) and then remained stable despite dose escalations. It was 16-23 times higher than in non-bathed tissues. Increasing doses of intraperitoneal irinotecan did not modify the PK of intraperitoneal oxaliplatin, and the drug concentration ratio was 17.8 higher in tumoral tissue (bathed) than in non-bathed tissues. The hospital mortality rate was 2.5% and the non-hematological complication rate was 25%. However, grade 3-4 hematological toxicity rate was 58%.
  
  
  CONCLUSIONS
  Intraperitoneal heated oxaliplatin (460 mg/m(2)) plus irinotecan (400 mg/m(2)) presented an advantageous PK profile and was tolerated by patients, despite a high hematological toxicity rate.
authors.affiliation: Department of Surgical Oncology, Institut Gustave Roussy Comprehensive Cancer Center, Villejuif, France.
authors.forename: D
authors.initials: D
authors.lastname: Elias
authors.forename: T
authors.initials: T
authors.lastname: Matsuhisa
authors.forename: L
authors.initials: L
authors.lastname: Sideris
authors.forename: G
authors.initials: G
authors.lastname: Liberale
authors.forename: L
authors.initials: L
authors.lastname: Drouard-Troalen
authors.forename: B
authors.initials: B
authors.lastname: Raynard
authors.forename: M
authors.initials: M
authors.lastname: Pocard
authors.forename: J M
authors.initials: JM
authors.lastname: Puizillou
authors.forename: V
authors.initials: V
authors.lastname: Billard
authors.forename: P
authors.initials: P
authors.lastname: Bourget
authors.forename: M
authors.initials: M
authors.lastname: Ducreux
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D002277:Carcinoma / Q000188:drug therapy* / Q000601:surgery; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D007263:Infusions, Parenteral; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics; D000077150:Oxaliplatin; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000601:surgery
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D002166:Camptothecin