Regional Isolated Limb Perfusion in Patients with Malignant Melanoma

In this overview the Amsterdam/Rotterdam ‘controlled’ normothermic (tissue temperatures 37-38°C) perfusion technique is described. The benefit of the widely used so-called ‘mild’ hyperthermia (39-40°C) is queried. A plea is made to report acute regional toxicity after perfusion according to Wieberdink’s grading system for uniformity. Perfusion has a well-established role in the treatment of locally inoperable melanoma. As an adjunct to surgery, benefit has also been shown in resectable stage II—III recurrent melanoma. For stage I primary melanoma the results of the ongoing EORTC/WHO adjuvant trials are eagerly awaited. In measurable disease an overall response rate of about 80% (with equal proportions of complete and partial remissions) can be obtained by single normothermic or ‘mild’ hyperthermic perfusion. Perfusion strategies that have been investigated to improve the complete response rate are discussed: the application of other cytostatics than melphalan, the role of repeat perfusions, perfusion with melphalan at borderline ‘true’ hyperthermic tem-peratures (40.5-42°C), sequential perfusion applying ‘true’ hyperthermia (42-43°C) and melphalan separately, and perfusion with the combination of rTNF-alpha, Inter- feron-gamma and melphalan. The ideal of a 100% complete remission rate has been approached in several perfusion strategies but the duration of remission is still rather short. The main issue for the immediate future will therefore be prolongation of the limb recurrence-free interval.