title: Histamine combined with melphalan in isolated limb perfusion for the treatment of locally advanced soft tissue sarcomas: preclinical studies in rats.
abstract: OBJECTIVE
  To evaluate the potential benefit of histamine combined with melphalan in the isolated limb perfusion (ILP) as an alternative to TNF-alfa and melphalan combination, for the treatment of irresectable soft tissue sarcomas of the limbs in Brown Norway (BN) rats.
  
  
  METHODS
  20 BN rats had small fragments of syngeneic BN-175 fibrosarcoma inserted on the right hind limb. In 7-10 days the tumor reached a median diameter of 12-15 mm and they were randomly divided in four groups (sham, melphalan, histamine and escalating doses of histamine combined to melphalan) being submitted to experimental ILP for 30 minutes. Tumors were measured daily with a caliper and the volume was calculated.
  
  
  RESULTS
  Response curves showed a significant effect of the combination of histamine 200 mg/mL with melphalan, with 66% overall response, including 33% complete responses (p< 0.01). There were no systemic collateral effects and locally only mild temporary edema was observed for some animals treated with histamine.
  
  
  CONCLUSIONS
  Histamine combined with melphalan had a promising effect in the ILP warranting future studies to better explore the mechanism of action as well as its potential use in organ perfusion.
authors.affiliation: Laboratory of Experimental Surgical Oncology, Daniel den Hoed Cancer Center, Erasmus MC, Rotterdam, The Netherlands. flis_br@yahoo.com
authors.forename: Flavia
authors.initials: F
authors.lastname: Brunstein
authors.forename: Ivan Dunshee de Abranches Oliveira
authors.initials: ID
authors.lastname: Santos
authors.forename: Lydia Masako
authors.initials: LM
authors.lastname: Ferreira
authors.forename: Sandra T
authors.initials: ST
authors.lastname: van Tiel
authors.forename: Alexander M M
authors.initials: AM
authors.lastname: Eggermont
authors.forename: Timo L M
authors.initials: TL
authors.lastname: Ten Hagen
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D010478:Chemotherapy, Cancer, Regional Perfusion; D005121:Extremities; D006632:Histamine / Q000008:administration & dosage*; D018494:Histamine Agents / Q000008:administration & dosage*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage*; D051381:Rats; D011914:Rats, Inbred BN; D012509:Sarcoma / Q000188:drug therapy*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D018494:Histamine Agents; D006632:Histamine; D008558:Melphalan