Regional treatment strategies for in-transit melanoma metastasis

For in-transit melanoma confined to the extremities, regional chemotherapy in the form of hyperthermic isolated limb perfusion and isolated limb infusion are effective treatment modalities carrying superior response rates to current standard systemic therapy. Despite high response rates, most patients will eventually recur, supporting the role for novel research aimed at improving durable responses and minimizing toxicity. Although the standard cytotoxic agent for regional chemotherapy is melphalan, alternative agents such as temozolomide are currently being tested, with promising preliminary results. Current strategies for improving chemosensitivity to regional chemotherapy are aimed at overcoming classic resistance mechanisms such as drug metabolism and DNA repair, increasing drug delivery, inhibiting tumor-specific angiogenesis, and decreasing the apoptotic threshold of melanoma cells. Concurrent with development and testing of these agents, genomic profiling and biomolecular analysis of acquired tumor tissue may define patterns of tumor resistance and sensitivity from which personalized treatment may be tailored to optimize efficacy. In this article rational strategies for treatment of in-transit melanoma are outlined, with special emphasis on current translational and clinical research efforts.