title: Isolated hypoxic hepatic perfusion with orthograde or retrograde flow in patients with irresectable liver metastases using percutaneous balloon catheter techniques: a phase I and II study.
abstract: BACKGROUND
  Isolated hepatic perfusion for irresectable metastases confined to the liver has reported response rates of 50% to 75%. Magnitude, costs, and nonrepeatability of the procedure are its major drawbacks. We developed a less invasive, less costly, and potentially repeatable balloon catheter-mediated isolated hypoxic hepatic perfusion (IHHP) technique.
  
  
  METHODS
  In this phase I and II study, 18 consecutive patients with irresectable colorectal or ocular melanoma hepatic metastases were included. Two different perfusion methods were used, both with inflow via the hepatic artery, using melphalan 1 mg/kg. In the first eight patients, the portal vein was occluded, and outflow was via the hepatic veins into an intracaval double-balloon catheter. This orthograde IHHP had on average 56% leakage. In next 10 patients, we performed a retrograde outflow IHHP with a triple balloon blocking outflow into the caval vein and allowing outflow via the portal vein. The retrograde IHHP still had 35% leakage on average.
  
  
  RESULTS
  Although local drug concentrations were high with retrograde IHHP, systemic toxicity was still moderate to severe. Partial responses were seen in 12% and stable disease in 81% of patients. The median time to local progression was 4.8 months.
  
  
  CONCLUSIONS
  We have abandoned occlusion balloon methodology for IHHP because it failed to obtain leakage control. We are presently conducting a study using a simplified surgical retrograde IHHP method, in which leakage is fully controlled, which translates into high response rates.
authors.affiliation: Department of Surgical Oncology, Erasmus University Medical Center-Daniel den Hoed Cancer Center, PO Box 5201, 3008 AE Rotterdam, The Netherlands.
authors.forename: Boudewijn
authors.initials: B
authors.lastname: van Etten
authors.forename: Flavia
authors.initials: F
authors.lastname: Brunstein
authors.forename: Marc G A
authors.initials: MG
authors.lastname: van IJken
authors.forename: Andreas W K S
authors.initials: AW
authors.lastname: Marinelli
authors.forename: Cornelis
authors.initials: C
authors.lastname: Verhoef
authors.forename: Joost R M
authors.initials: JR
authors.lastname: van der Sijp
authors.forename: Gunther
authors.initials: G
authors.lastname: Guetens
authors.forename: Gert
authors.initials: G
authors.lastname: de Boeck
authors.forename: Ernst A
authors.initials: EA
authors.lastname: de Bruijn
authors.forename: Johannes H W
authors.initials: JH
authors.lastname: de Wilt
authors.forename: Alexander M M
authors.initials: AM
authors.lastname: Eggermont
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002404:Catheterization / Q000379:methods*; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000295:instrumentation / Q000379:methods*; D015179:Colorectal Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008875:Middle Aged; D015996:Survival Rate
chemical_list: D018906:Antineoplastic Agents, Alkylating; D008558:Melphalan