title: Hepatic vascular isolation and perfusion for patients with progressive unresectable liver metastases from colorectal carcinoma refractory to previous systemic and regional chemotherapy.
abstract: BACKGROUND
  Many patients with colorectal carcinoma develop unresectable metastases confined to the liver that remain the life-limiting component of disease despite best available systemic or regional chemotherapy. In the current study, the authors present their results using vascular isolation and perfusion of the liver for individuals with progressive, unresectable liver metastases from colorectal carcinoma that were refractory to both previous systemic and regional chemotherapy.
  
  
  METHODS
  Seven patients with refractory, progressive, unresectable colorectal carcinoma metastases confined to the liver underwent a 60-minute hyperthermic (39-40 degrees C) isolated hepatic perfusion (IHP) and were followed for toxicity, response, and survival.
  
  
  RESULTS
  There was no surgical- or treatment-related mortality; all patients experienced transient Grade 3-4 (according to National Cancer Institute common toxicity criteria) hepatic toxicity. At a median potential follow-up of 16 months, the overall objective radiographic response rate (all partial responses) was 71% (5 of 7 assessable patients). It is interesting to note that two patients who were treated with tumor necrosis factor (TNF) alone demonstrated no response to therapy compared with all five patients who were treated with melphalan and TNF (three patients) or melphalan alone (two patients). For the 5 patients who responded to treatment, the median duration of response was 10 months (range, 10-13 months) and in all 7 patients the mean overall survival was 19.7 months (range, 2-33 months), including 5 months and 7.5 months, respectively, for the 2 patients treated with TNF alone.
  
  
  CONCLUSIONS
  The results of the current study demonstrate that IHP using melphalan with or without TNF has significant antitumor activity in this patient population. IHP deserves continued clinical evaluation as a therapeutic modality for patients with unresectable colorectal carcinoma metastases to the liver.
authors.affiliation: Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Richard_Alexander@nih.gov
authors.forename: H Richard
authors.initials: HR
authors.lastname: Alexander
authors.forename: Steven K
authors.initials: SK
authors.lastname: Libutti
authors.forename: David L
authors.initials: DL
authors.lastname: Bartlett
authors.forename: James F
authors.initials: JF
authors.lastname: Pingpank
authors.forename: Karen
authors.initials: K
authors.lastname: Kranda
authors.forename: Cynthia
authors.initials: C
authors.lastname: Helsabeck
authors.forename: Tatiana
authors.initials: T
authors.lastname: Beresnev
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002277:Carcinoma / Q000188:drug therapy*; D010478:Chemotherapy, Cancer, Regional Perfusion; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000473:pathology*; D019008:Drug Resistance, Neoplasm; D006503:Hepatic Veins; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage
chemical_list: D000970:Antineoplastic Agents; D014409:Tumor Necrosis Factor-alpha; D008558:Melphalan