Although surgery with or without adjuvant therapy can be curative in early-stage melanoma, the outlook for patients with distant metastases remains bleak. Median survival in most series ranges from 6 to 9 months, with 5-year survival rates of under 4%.<sup>2Ahmed I. Malignant melanoma: Prognostic indicators Mayo Clin Proc 1997 ;  72 : 356-361

Cliccare qui per andare alla sezione Riferimenti</sup> Although a variety of cytotoxic chemotherapy agents used either alone or in combination possess activity against metastatic melanoma, responses are usually partial and of short duration. In particular, combination cytotoxic chemotherapy results in 5-year durable responses in only 1% to 2% of patients,<sup>53Hill G.J., Krementz E.T., Hill H.Z. Dimethyl triazeno imidazole carboxamide and combination therapy for melanoma. IV. Late results after complete response to chemotherapy (Central Oncology Group protocols 7130, 7131, and 7131A) Cancer 1984 ;  53 : 1299-1305 [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> and has yet to be shown superior to dacarbazine alone in a randomized phase III trial<sup>11Atkins M.B. The role of cytotoxic chemotherapeutic agents either alone or in combination with biological response modifiers Molecular Diagnosis, Prevention & Therapy of Melanoma New York: Marcel Dekker (1998).  219-251

Cliccare qui per andare alla sezione Riferimenti</sup> (see the article by Drs. Green and Schuchter on p. 863 of this issue). Thus, new approaches to the treatment of metastatic melanoma are clearly necessary.

Clinical and laboratory observations have suggested that host immunologic responses may occasionally influence the course of melanoma, and have stimulated interest in the use of biologic response modifiers in this disease. The entire repertoire of immunotherapeutic approaches has been explored, and many approaches have shown some antitumor and/or immunomodulatory activity. Areas of active investigation include recombinant cytokines (either alone or in combination with adoptive immunotherapy, toxicity reduction agents, or cytotoxic chemotherapy), vaccines, monoclonal antibodies or antibody conjugates, and gene therapy. This article reviews the clinical investigations with these various approaches in metastatic melanoma and their current and potential role in this disease.