ISOLATED PERFUSION OF THE LIMB WITH HIGH-DOSE TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA), INTERFERON-GAMMA (IFN-GAMMA) AND MELPHALAN FOR MELANOMA STAGE-III - RESULTS OF A MULTICENTER 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 ha d stage IV melanoma. Most of them had more than five in-transit metast ases; 50% had been previously treated by regional chemotherapy. Protoc ol included 90-min isolation perfusion at 40-degrees-C with 2-4 mg rTN F-alpha, 0.2 mg rIFN-gamma and 10/13 mg/l melphalan. We prevented seve re TNF systemic side effects by administration of dopamine and fluid l oading. There has been no toxic death and the toxicity remained accept able, with only one multi-organ failure (MOF) and no prolonged shock. Response rates remained very high, with 90% complete remission, 10% pa rtial response and no failure. With a median follow-up time of 26 mont hs, there were 12 regional recurrences, 15 distant metastases and nine local and distant recurrences. The median overall survival has been 2 8 months. We conclude that high-dose rTNF-alpha associated with melpha lan in isolation perfusion is the therapy of choice for in-transit mel anoma metastases.