ISOLATED LIMB PERFUSION IN PRIMARY AND RECURRENT MELANOMA - INDICATIONS AND RESULTS

In advanced melanoma of the limbs with in-transit metastasis, melphala n with isolated limb perfusion (M-ILP) produces around 50% complete re missions (CR). The combination of melphalan with tumour necrosis facto r-alpha (TNF alpha) and interferon-gamma (IFN gamma) in isolated limb perfusion (TIM-ILP) gives around 80% CR. A prospective randomised phas e II study compared 32 patients who received TIM-ILP with 32 patients who received TM-ILP (without IFN gamma). The overall remission rate (O RR) and the CR rate were superior with TIM-ILP as compared to TM-ILP, 100% vs. 91% and 78% vs. 69% respectively, but the differences are not significant. Given the efficacy of M-ILP on in-transit metastasis, th e procedure was tested as an adjunct to surgery in high-risk (Breslow greater than or equal to 1.5 mm) primary melanoma of the limbs. Throug h the combined effort of the melanoma groups of the European Organizat ion for Research arid Treatment of Cancer (EORTC), the World Health Or ganization (WHO), and the North American Perfusion Group, 832 evaluabl e patients from 16 centres were entered in a phase III study. Median f ollowup is 6.4 years. There was a trend for a longer disease-free inte rval after M-ILP. The difference is significant if the patients withou t elective lymph node dissection (ELND) are separately analysed, with a high significance in the 1.5 to 3 mm thickness subgroup. The occurre nce of in-transit metastases was reduced from 6.6% to 3.3% by M-ILP. T here was, however, no benefit of M-ILP in terms of survival. Prophylac tic M-ILP cannot be recommended as a standard adjunct to surgery in hi gh-risk primary limb melanoma. TIM-ILP or TM-ILP is a regional therapy with a very high regional response rate on melanoma in-transit metast asis. (C) 1998 Wiley-Liss, Inc.