Melanoma - Immunotherapeutic approaches

The incidence of melanoma in the US is rising at a rate second only to that of lung cancer in women. Early stage melanoma is curable, but once metasta tic, it is almost uniformly fatal. The immunotherapy of melanoma is a new a nd exciting therapeutic modality that is being extensively investigated wor ldwide. Interferon-alpha has an approximately 16% response rate in metastatic melan oma. In the randomised trials to date, no combination of chemotherapeutic o r hormonal agent with interferon-alpha has proven to be superior to dacarba zine, the reference agent for the treatment of metastatic melanoma. The rol e of interferon-alpha-2b in the adjuvant therapy of localised melanoma at h igh risk for relapse has recently been established, with the results of 2 l arge randomised trials conducted by the US Intergroup, one showing improvem ent in both relapse-free survival and over-all survival, and the other in r elapse-free survival only. Interferon-gamma has not been effective in the a djuvant setting or in metastatic disease, but is part of combination protoc ols used for regional therapy for extremity melanomas. Interleukin-2 has an overall response rate of 15 to 20% in metastatic melan oma and produces some complete and durable remissions. The US Food and Drug Administration has recently approved the use of high-dose bolus administra tion of recombinant interleukin-2, for the therapy of metastatic melanoma. Results of combination chemotherapy and immunotherapy regimens containing i nterleukin-2 (biochemotherapy) are promising, and ongoing research will det ermine whether a survival impact will be confirmed in randomised studies. Vaccine therapy is another exciting area of research, and clinical trials a re ongoing in both metastatic melanoma and as adjuvant therapy. A bewilderi ng array of vaccines (whole cell, carbohydrate and peptide) is available, a nd it remains to be seen which of these numerous preparations will be most effective. Adjuvant therapy trials with a ganglioside GM2 vaccine and other s are ongoing. Numerous peptide vaccines are also being investigated for me tastatic melanoma, singly and in combination with other immunotherapeutic a gents.