Isolated perfusion of the limb with high-dose tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and melphalan for melanoma stage III. Results of a multi-centre pilot study.
We report an update of a multi-centre pilot study previously published. Fifty-three patients (42 women, 11 men) were accrued between October 1988 and May 1992: 34 had stage IIIA, 15 had stage IIIAB, and four had stage IV melanoma. Most of them had more than five in-transit metastases; 50% had been previously treated by regional chemotherapy. Protocol included 90-min isolation perfusion at 40 degrees C with 2-4 mg rTNF-alpha, 0.2 mg rIFN-gamma and 10/13 mg/l melphalan. We prevented severe TNF systemic side effects by administration of dopamine and fluid loading. There has been no toxic death and the toxicity remained acceptable, with only one multi-organ failure (MOF) and no prolonged shock. Response rates remained very high, with 90% complete remission, 10% partial response and no failure. With a median follow-up time of 26 months, there were 12 regional recurrences, 15 distant metastases and nine local and distant recurrences. The median overall survival has been 28 months. We conclude that high-dose rTNF-alpha associated with melphalan in isolation perfusion is the therapy of choice for in-transit melanoma metastases.
Centre Pluridisciplinaire d'Oncologie, CHUV, Lausanne, Switzerland.
D
D
Liénard
A M
AM
Eggermont
H
H
Schraffordt Koops
B B
BB
Kroon
F
F
Rosenkaimer
P
P
Autier
F J
FJ
Lejeune
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D010478:Chemotherapy, Cancer, Regional Perfusion; D004305:Dose-Response Relationship, Drug; D005121:Extremities; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D010865:Pilot Projects; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D008558:Melphalan