Isolated limb perfusion with fotemustine after chemosensitization with dacarbazine in melanoma

Isolated limb perfusion (ILP) has been reported as the most effective treatment for localized recurrent melanoma of the limbs. In terms of local and regional control with melphalan, complete remission is achieved in about 40% of patients, with frequent toxicity causing significant short-term disability in many and long-term incapacity in a few. Since 1989, several studies have reported success using a combination of fotemustine and dacarbazine (DTIC) in the systemic treatment of disseminated melanoma and brain metastasis. In May 1995, we began a pilot study with systemic DTIC 400 mg/m2 given intravenously about 4 h before ILP using fotemustine in an intra-arterial bolus of 100-150 mg/m2 as the perfusion agent. By July 1996, 10 patients had been included in the study. The results were evaluated in terms of the response rate (five complete responses and one partial response in the six patients who could be evaluated), local toxicity (nine patients with level I and one with level II, measured on the Wieberdink scale) and systemic toxicity (nine patients with level 0 and one with level 1, measured on the World Health Organization scale). Treatment was effective, with a similar response rate to that obtained with melphalan but with much lower toxicity, so this protocol may represent an innovation in loco-regional therapy and should be further investigated in a large trial.