ISOLATED LIMB REPERFUSION WITH TUMOR-NECROSIS-FACTOR AND MELPHALAN INPATIENTS WITH EXTREMITY MELANOMA AFTER FAILURE OF ISOLATED LIMB PERFUSION WITH CHEMOTHERAPEUTICS

BACKGROUND, This retrospective study evaluated the benefit of using tu mor necrosis factor (TNF) and melphalan administered via an isolated l imb perfusion (ILP) in a series of patients with metastatic melanoma w ho failed initial ILP with chemotherapeutics. METHODS. Seventeen patie nts with extremity melanoma who underwent prior ILP with conventional chemotherapeutics (10 with melphalan; 4 with platinum; 2 with platinum , dacarbazine, thiotepa, actinomycin D, and nitrogen mustard; and 1 wi th thiotepa, actinomycin D, and nitrogen mustard) and had local recurr ences were treated with a 90-minute isolated hyperthermic limb reperfu sion with melphalan (10 mg/L limb volume) plus TNF (2-6 mg). Five prio r ILPs were adjuvant and 12 were therapeutic. RESULTS. Reperfusion was associated with an overall 94% response rate and a 65% complete respo nse (CR) rate. Of the patients who failed an initial ILP with melphala n alone the overall response rate was 90% after the reperfusion with T NF and melphalan. In patients who failed an initial ILP with agents ot her than melphalan the CR rate was 100% after ILP with TNF and melphal an. TNF/melphalan isolated limb reperfusion was found to be more effec tive in terms of CR after initial ILP regimens that did not utilize me lphalan (100% CR after nonmelphalan ILP vs. 50% CR after melphalan ILP [P = 0.04]). Regional toxicity was comprised of mild skin blistering and peeling in 47% of patients. One patient developed Grade 3 (based o n National Cancer Institute Common Toxicity Criteria) skin necrosis, a nd one developed Grade 5 muscle and nerve toxicity, requiring an amput ation. CONCLUSIONS. Isolated limb reperfusion with TNF and melphalan c an be performed safely with response rates similar to those of other t rials of single perfusions. Repeat ILP using TNF and melphalan in pati ents with melanoma who have failed prior ILP with chemotherapeutics is justified. The utility of TNF (vs. melphalan alone) will be defined i n ongoing Phase III trials. (C) 1997 American Cancer Society.