Impact of regional chemotherapy for melanoma metastases

Metastatic malignant melanoma requires sophisticated delineation of therapeutic approaches in order that palliation of the disease should be managed effectively. To date, systemic chemotherapy for melanoma metastases appears to be of only limited benefit, since tumoricidal drug levels can hardly be achieved in a way to overcome primary or secondary drug resistance of melanoma cells. With respect to topographically defined patterns of metastasis, therapeutic approaches introducing regional chemotherapy have recently promised improved palliation in the management of advanced solid tumors including melanoma. Among these approaches, isolated limb perfusion has become a well-established procedure in the treatment of melanoma which has metastasized to the extremities. The adjuvant setting of this technique is currently under investigation, and suggests a beneficial outcome in perfused high-risk patients. Intraarterial infusion techniques with or without regional venous drug hemofiltration might provide high cytotoxic tissue levels at the target region, thus subsequently leading to enhanced cell kill rates evidenced in terms of clinical responses. Angioocclusive approaches using persistent (chemoembolization) or transient (microspheres, liposomes) blocking techniques with subsequent reduction of the arterial/arteriolar blood flow may optimize the pharmacological advantage of regional drug delivery. In addition to cytoreductive surgery and systemic chemotherapy, the above-mentioned approaches of regional chemotherapy offer a new perspective in the palliative management of metastatic melanoma.