title: Continuous hyperthermic peritoneal perfusion with cisplatin for the treatment of peritoneal mesothelioma.
abstract: OBJECTIVE
  Peritoneal mesothelioma remains a difficult therapeutic challenge. Aggressive debulking combined with continuous hyperthermic peritoneal perfusion (CHPP) using cisplatin (CDDP) is a novel strategy for the treatment of peritoneal mesothelioma, allowing high regional delivery of chemotherapeutics and hyperthermia while minimizing systemic toxicity.
  
  
  METHODS
  From June 1993 to May 1996, 10 patients with peritoneal mesothelioma (six men, four women; mean age 40 years, range 15-57) underwent tumor debulking followed by a 90-minute CHPP. CHPP parameters included mean initial CDDP of 120 micrograms/mL (range 81-166), perfusate volume 5.2 L (range 4-7), flow 1.5 L/min, intraperitoneal temperature at three locations-41.5 degrees C, 40.5 degrees C, 41.1 degrees C, and core temperature 38.4 degrees C (range 37.2 degrees C-39.5 degrees C). Nine of 10 patients had malignant peritoneal mesothelioma, eight with associated ascites, while the tenth had a symptomatic, multiply recurrent benign peritoneal mesothelioma. Nine of 10 patients were optimally debulked. Pharmacokinetics were performed on blood and perfusate samples on nine patients; CDDP levels were quantitated by atomic absorption spectroscopy.
  
  
  RESULTS
  Total perfusate cisplatin AUC was a mean of 21-fold higher (range 2- to 116-fold) than total serum cisplatin AUC, and serum CDDP behaved similarly to systemically administered CDDP. Median follow-up after CHPP is 10 months (range 2-32), with no treatment-related mortality. In eight optimally debulked patients there is no evidence of recurrent disease clinically or by CT or MRI. Seven patients with symptomatic ascites have been completely palliated.
  
  
  CONCLUSIONS
  CHPP with CDDP is well tolerated with no significant regional toxicity. Because favorable CDDP pharmacokinetics suggest the potential for enhanced CDDP tumoricidal effect during CHPP, tumor debulking and CHPP may represent an effective strategy for the treatment of peritoneal mesothelioma.
authors.affiliation: Metabolism Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: G Y
authors.initials: GY
authors.lastname: Ma
authors.forename: D L
authors.initials: DL
authors.lastname: Bartlett
authors.forename: E
authors.initials: E
authors.lastname: Reed
authors.forename: W D
authors.initials: WD
authors.lastname: Figg
authors.forename: R M
authors.initials: RM
authors.lastname: Lush
authors.forename: K B
authors.initials: KB
authors.lastname: Lee
authors.forename: S K
authors.initials: SK
authors.lastname: Libutti
authors.forename: H R
authors.initials: HR
authors.lastname: Alexander
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000097:blood / Q000627:therapeutic use* / Q000633:toxicity; D010478:Chemotherapy, Cancer, Regional Perfusion; D002945:Cisplatin / Q000097:blood / Q000627:therapeutic use* / Q000633:toxicity; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000601:surgery; D008875:Middle Aged; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000601:surgery; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin