MAXIMIZING EFFICACY AND MINIMIZING TOXICITY IN ISOLATED LIMB PERFUSION FOR MELANOMA

Isolated limb perfusion (ILP) with melphalan is an effective treatment for recurrent melanoma, but complete remission is achieved only in ab out 40% of patients. Regional toxicity is common, causing short-term d isability and occasional long-term incapacity. Methods to maximize the efficacy and minimize the toxicity were investigated in 210 ILPs unde rtaken at the Sydney Melanoma Unit. Toxicity was found to be related t o peak melphalan concentration, as well as to the area under the curve and maximum temperature. A dye dilution technique has been developed to measure perfusion circuit volume, so that a drug dose can be given to achieve an appropriate concentration. ILP with cisplatin was less e ffective and produced greater toxicity then ILP with melphalan; other drugs and drug combinations warrant investigation. Prophylactic ondans etron successfully controlled post-operative nausea and vomiting in mo st patients. Daily measurement of serum creatine phosphokinase (CPK) a llowed early recognition of impending severe toxicity, with the greate st risk if CPK exceeded 1000 IU/l after the first post-perfusion day. Isolated limb 'infusion' (ILI) with melphalan, using percutaneously in serted catheters, is a much simpler procedure than ILP and has been fo und to be effective and easily repeated. The morbidity of ILP and ILI may be minimized by excluding the foot or hand with a rubber bandage.