In transit metastases of malignant melanoma treated by high dose rTNF alpha in combination with interferon-gamma and melphalan in isolation perfusion.
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)
Liénard
D
D
Department of Surgery, Jules Bordet Institute, Université Libre de Bruxelles, Belgium.
Lejeune
F J
FJ
Ewalenko
P
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000009:adverse effects / Q000379:methods; D004298:Dopamine / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006979:Hyperthermia, Induced; D007371:Interferon-gamma / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008207:Lymphatic Metastasis / Q000473:pathology / Q000517:prevention & control; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary* / Q000628:therapy; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009367:Neoplasm Staging; D011994:Recombinant Proteins; D012074:Remission Induction; D012769:Shock / Q000517:prevention & control; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D008558:Melphalan; D004298:Dopamine