Malignant Melanoma: Current Therapeutic Concepts

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Abstract
The number of therapeutic concepts for treatment of malignant melanoma is continuously growing, and new insights into the mechanism of treatment approaches have been gained. Depending on the clinical stage of the disease local, regional or systemic treatment modalities can be administered in a curative, adjuvant or palliative setting. The only possibility to cure a melanoma is to detect the primary tumor in a very early phase of development and immediately remove it. Adjuvant therapy options have been followed for years and can be divided into subgroups such as historical approaches like BCG (bacille Calmette-Guérin), levamisole, pre- and postoperative radiation of the primary tumor, endolymphatic radionuclid therapy or extended safety margins. ‘Standard’ therapies have been carried out within study protocols, e.g. elective lymph node dissection or extremity perfusion. Recent strategies such as the application of cytokines and tumor or antigen vaccines are still being investigated. As none of the results shows a definite advantage of one or the other kind of treatment, adjuvant therapy should only be done within study protocols. Metastatic melanoma remains incurable yet highly treatable. When critically analyzing the results, certain protocols are regarded as standard therapy for palliative treatment: surgery, radiotherapy, and chemotherapy. Other therapy strategies, some of them have been used for a long time (e.g. multimodality treatment), may improve tumor remission rates and long-term survival, but obviously further randomized prospective trials are needed. There are even more experimental therapy concepts such as stereotactic single high-dose irradiation, photodynamic therapy, the application of a new generation of monoclonal antibodies or gene therapy. Current therapy protocols emphasize the reduction of toxicity. The question has been raised whether the paradigm of tumor killing, as nowadays postulated for curing the patient, may be counter-productive as it impairs host response. Efforts will have to be made to unravel differences in therapy results between single institution and multicenter studies and make different schedules containing the same drugs comparable as well as define the patient population benefiting from a certain form of therapy. Continuous research in molecular biology and tumor immunology has enhanced our understanding of malignant melanoma and may help to develop a more specific, effective, and less toxic therapy.

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