DETERMINANTS OF ACUTE REGIONAL TOXICITY FOLLOWING ISOLATED LIMB PERFUSION FOR MELANOMA

Hyperthermic isolated limb perfusion (ILP) with melphalan is well esta blished as an effective form of treatment for recurrent melanoma confi ned to an extremity. High drug concentrations in the limb are readily achieved, without systemic side-effects. However, regional toxicity ca n lead to considerable morbidity and functional disturbance. This stud y was undertaken to evaluate factors which might contribute to acute r egional toxicity following ILP. Melphalan concentrations in limb blood samples taken at regular intervals during 135 ILPs were measured by H PLC, allowing peak melphalan concentration and area under the curve (A UC) for each procedure to be determined. Acute regional toxicity assoc iated with ILP was found to be significantly correlated with limb tiss ue temperatures >40 degrees C, peak melphalan concentration and melpha lan AUC, in decreasing order, but was not correlated with tourniquet t ime. Further studies are required to directly assess melphalan uptake by tumour tissue, and to relate this to both limb toxicity and tumour response.