title: Phase II study of regional chemotherapy using the hypoxic abdominal perfusion technique in advanced abdominal carcinoma. 5-FU pharmacokinetics, complications and outcome.
abstract: The aim of this study was to verify the rationale of a hypoxic abdominal perfusion (HAP) technique for the perfusion of 5-FU, mitomycin C and cisplatin in patients with inoperable, recurrent abdominal cancer.
  
  
  METHODS
  In a phase II study, 59 patients with various non-resectable abdominal tumours were treated with 102 perfusions by the HAP-technique. The HAP-technique was performed by using double-balloon arterial-venous catheters that selectively isolated the abdominal vascular section and perfusion was provided by an extracorporal pump for 20 min. Thirty-four patients with unresectable colorectal cancer, 11 with unresectable gastric cancer, eight with unresectable pancreatic cancer and six with cancer of the gall bladder were included. They were treated with a combination of 5-fluorouracil (5-FU 1 g/m(2)), mitomycin C (MMC, 10 mg/m(2)) plus cisplatin (50 mg/m(2)) infused into the isolated abdominal compartment. The cytostatic concentration of 5-FU was determined intrainterventionally within the systemic and regional compartment. Toxicity- and procedure-related complications were documented. Tumour responses were assessed by computer tomography.
  
  
  RESULTS
  5-FU concentration was 16.3-fold higher within the regional compared to the systemic compartment at its maximum, and the area under the curve (AUC) was 7.9 times larger. During the procedure two major complications were experienced (1x perforation of the A. iliaca, lx deep vein thrombosis), no deaths occurred during surgery or in the postoperative period. Minimal systemic and local toxicities were observed (WHO grade III-IV 1%, grade I-II 33%). No complete response but 22 partial responses were observed. Median survival was 15.5 months for colorectal cancer, 12. 5 months for gastric cancer, 12.7 months for pancreatic cancer and 7.8 months for gall bladder cancer.
  
  
  CONCLUSIONS
  The hypoxic abdominal perfusion is a safe and effective palliative treatment for patients with unresectable advanced colorectal, gastric and pancreatic carcinoma. The HAP has not shown promising results for advanced gall bladder cancer. These encouraging clinical results require further evaluation.
authors.affiliation: Department of Surgery, University of Berlin, Charité Campus Benjamin Franklin, Berlin, Germany. SU1110@aol.com
authors.forename: U
authors.initials: U
authors.lastname: Pohlen
authors.forename: H
authors.initials: H
authors.lastname: Rieger
authors.forename: S
authors.initials: S
authors.lastname: Kunick-Pohlen
authors.forename: G
authors.initials: G
authors.lastname: Berger
authors.forename: H J
authors.initials: HJ
authors.lastname: Buhr
mesh_terms: D000008:Abdominal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019540:Area Under Curve; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000295:instrumentation / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000473:pathology; D003967:Diarrhea / Q000139:chemically induced; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D000860:Hypoxia; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D009325:Nausea / Q000139:chemically induced; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
chemical_list: D016685:Mitomycin; D002945:Cisplatin; D005472:Fluorouracil