In transit metastases of malignant melanoma treated by high dose rTNF alpha in combination with interferon-gamma and melphalan in isolation perfusion

World J Surg. Mar-Apr 1992;16(2):234-40. doi: 10.1007/BF02071526.


To increase the therapeutic efficacy of recombinant tumor necrosis factor alpha (rTNF alpha) and reduce the systemic side effects, a protocol was designed using isolation perfusion of the limbs with hyperthermia for in transit metastases of melanoma. A triple combination of high dose rTNF alpha + recombinant interferon-gamma (rIFN-gamma) + melphalan was chosen because of a synergistic anti-tumor effect of rTNF alpha with rIFN-gamma and of rTNF alpha with alkylating agents reported in the literature. Twenty-nine patients of mean age 60 years (range 22-82 years) entered the study after informed consent and received a total of 31 isolation perfusions with the triple combination. There were 24 women and 5 men with multiple progressive in transit melanoma metastases of the lower limb (stage IIIa or IIIab). rTNF alpha at the unique dose of 4 mg was injected as a bolus in the arterial line, under mild hyperthermic conditions (40 to 40.5 degrees C) for 90 minutes. rIFN-gamma was given subcutaneously on days -2 and -1 and in the perfusate, with rTNF alpha, at the dose of 0.2 mg. Melphalan was administered in the perfusate at dose giving a concentration of 40 micrograms/ml. In all the 31 isolation perfusions performed in the triple combination protocol, in order to prevent a septic shock-like syndrome which had been encountered in 2 patients treated outside this protocol for sarcoma and carcinoma, the patients received dopamine continuous infusion at 3 micrograms/kg/min from the start of isolation perfusion and for 48 hours, and only showed mild hypotension and very transient chills and temperature.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Chemotherapy, Cancer, Regional Perfusion* / adverse effects
  • Chemotherapy, Cancer, Regional Perfusion* / methods
  • Dopamine / therapeutic use
  • Female
  • Follow-Up Studies
  • Humans
  • Hyperthermia, Induced
  • Interferon-gamma / administration & dosage
  • Interferon-gamma / adverse effects
  • Interferon-gamma / therapeutic use*
  • Lymphatic Metastasis* / pathology
  • Lymphatic Metastasis* / prevention & control
  • Male
  • Melanoma / drug therapy*
  • Melanoma / pathology
  • Melanoma / secondary*
  • Melanoma / therapy
  • Melphalan / administration & dosage
  • Melphalan / adverse effects
  • Melphalan / therapeutic use*
  • Middle Aged
  • Neoplasm Staging
  • Recombinant Proteins
  • Remission Induction
  • Shock / prevention & control
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / pathology
  • Skin Neoplasms / therapy
  • Tumor Necrosis Factor-alpha / administration & dosage
  • Tumor Necrosis Factor-alpha / adverse effects
  • Tumor Necrosis Factor-alpha / therapeutic use*


  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Melphalan
  • Dopamine