title: Isolated hepatic perfusion with tumor necrosis factor and melphalan for unresectable cancers confined to the liver.
abstract: OBJECTIVE
  To evaluate the efficacy and systemic and regional toxicities of hyperthermic isolated hepatic perfusion (IHP) using tumor necrosis factor (TNF) and melphalan for the treatment of unresectable primary or metastatic cancers confined to the liver.
  
  
  METHODS
  Thirty-four patients (18 men and 16 women; mean age, 49 years) underwent a 60-minute hyperthermic (39.5 degrees to 40.0 degrees C) IHP performed by laparotomy that used TNF 1.0 mg and melphalan 1.5 mg/kg. Perfusion inflow was through the gastroduodenal artery and outflow was from a cannula positioned in an isolated segment of retrohepatic inferior vena cava (IVC). Infrahepatic IVC and portal venous blood flow were shunted to the axillary vein using an external venoveno bypass circuit. Complete vascular isolation of the liver was confirmed by an I-131-labelled human serum albumin monitoring technique.
  
  
  RESULTS
  There was no operative mortality. Seventy-five percent of patients had reversible grade III or IV (National Cancer Institute Common Toxicity Criteria) hepatic toxicity with one treatment-related mortality (3%) because of hepatic venoocclusive disease. In 33 assessable patients, the overall response rate was 75% (complete response, one patient [3%]; partial response, 26 patients [72%]). With a median potential follow-up of 15 months, the mean duration of response was 9 months (range, 2 to 30 months).
  
  
  CONCLUSIONS
  IHP with TNF and melphalan results in significant regression of bulky hepatic cancers confined to the liver in the majority of patients. Based on these initial results, further refinement of this treatment technique is warranted; perhaps by the combination of IHP with other regional treatment strategies to provide long-term control of unresectable cancers confined to liver.
authors.affiliation: Surgical Metabolism Section, Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1502, USA. hra@pop.nci.nih.gov
authors.forename: H R
authors.initials: HR
authors.lastname: Alexander
authors.forename: D L
authors.initials: DL
authors.lastname: Bartlett
authors.forename: S K
authors.initials: SK
authors.lastname: Libutti
authors.forename: D L
authors.initials: DL
authors.lastname: Fraker
authors.forename: T
authors.initials: T
authors.lastname: Moser
authors.forename: S A
authors.initials: SA
authors.lastname: Rosenberg
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000009:adverse effects; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000379:methods*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000556:secondary / Q000628:therapy*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D000637:Transaminases / Q000378:metabolism; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D018906:Antineoplastic Agents, Alkylating; D014409:Tumor Necrosis Factor-alpha; D000637:Transaminases; D008558:Melphalan