title: Palliation of regional symptoms of advanced extremity melanoma by isolated limb perfusion with melphalan and high-dose tumor necrosis factor.
abstract: OBJECTIVE
  Bulky, symptomatic melanoma of the extremity is a difficult management problem. In some patients, slowly progressive yet extensive regional disease can produce pain, edema, bleeding, and immobility. The use of hyperthermic isolated limb perfusion may provide good regional palliation even in the presence of distant metastatic disease. This study evaluates the ability of isolated limb perfusion using melphalan and high-dose tumor necrosis factor to palliate regional symptoms of locally advanced extremity melanoma.
  
  
  METHODS
  Fifteen patients with symptomatic extremity melanoma were treated for 90 minutes with isolated limb perfusion using mild hyperthermia, tumor necrosis factor at a dose of 4 mg (n = 8) or 6 mg (n = 7) given at the initiation of perfusion, and melphalan, 10 mg/L limb volume, given at 30 minutes into the perfusion. Eleven patients also received three courses of low-dose gamma-interferon, 0.2 mg subcutaneously, once a day for the 2 days preceding surgery and at the initiation of perfusion.
  
  
  RESULTS
  Symptomatic improvement was achieved in 9 of 11 patients who had pain, 6 of 6 patients with edema, 5 of 6 patients with decreased extremity mobility, and 5 of 6 with bleeding or severe ulceration. The objective response rate in 14 evaluable patients was 100%, with a complete response rate in 5 of 14. Twelve of 15 patients achieved local control of advanced extremity melanoma after isolated limb perfusion. Treatment-related systemic toxicities were minimal and short lived.
  
  
  CONCLUSIONS
  Isolated limb perfusion with melphalan and tumor necrosis factor is an effective and safe palliative treatment of locally advanced symptomatic melanoma of the extremity.
authors.affiliation: Surgical Metabolism Section, Surgery Branch, National Cancer Institute, Clinical Center, National Institutes of Health, Bethesda, MD 20892-1502, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Fraker
authors.forename: H R
authors.initials: HR
authors.lastname: Alexander
authors.forename: M
authors.initials: M
authors.lastname: Andrich
authors.forename: S A
authors.initials: SA
authors.lastname: Rosenberg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D010478:Chemotherapy, Cancer, Regional Perfusion; D003131:Combined Modality Therapy; D005121:Extremities; D005260:Female; D006801:Humans; D007036:Hypothermia, Induced; D007371:Interferon-gamma / Q000008:administration & dosage; D008297:Male; D008545:Melanoma / Q000628:therapy*; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D010166:Palliative Care; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage
chemical_list: D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D008558:Melphalan