CLINICAL-EXPERIENCE WITH HIGH-DOSE TUMOR-NECROSIS-FACTOR-ALPHA IN REGIONAL THERAPY OF ADVANCED MELANOMA

Isolated perfusion of the limbs (ILP) allows the delivery of high dose rTNF alpha in a closed system with acceptable side-effects. A protoco l with a triple-drug regimen was based on the reported synergism of rT NF alpha with chemotherapy, with interferon-gamma, and with hypertherm ia. In melanoma-in-transit metastases (stage IIIA or AB) we obtained a 91% complete response compared with 52% after ILP with melphalan alon e. Leakage and release of nanograms levels of TNF alpha in the systemi c circulation can be abrogated in most patients by low pump flow, cont inuous leak monitoring, extensive washout, and limb massage. In case o f unavoidable leakage, appropriate intensive care results in minimal t oxicity. The ILP with rTNF alpha appears to be a useful model for stud ying the biochemotherapy of cancer in humans. (C) 1994 Wiley-Liss, Inc .