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 metastatic, it is almost uniformly fatal. The immunotherapy of melanoma is a new and exciting therapeutic modality that is being extensively investigated worldwide. Interferon-alpha has an approximately 16% response rate in metastatic melanoma. In the randomised trials to date, no combination of chemotherapeutic or hormonal agent with interferon-alpha has proven to be superior to dacarbazine, the reference agent for the treatment of metastatic melanoma. The role of interferon-alpha-2b in the adjuvant therapy of localised melanoma at high risk for relapse has recently been established, with the results of 2 large randomised trials conducted by the US Intergroup, one showing improvement in both relapse-free survival and overall survival, and the other in relapse-free survival only. Interferon-gamma has not been effective in the adjuvant setting or in metastatic disease, but is part of combination protocols used for regional therapy for extremity melanomas. Interleukin-2 has an overall response rate of 15 to 20% in metastatic melanoma and produces some complete and durable remissions. The US Food and Drug Administration has recently approved the use of high-dose bolus administration of recombinant interleukin-2 for the therapy of metastatic melanoma. Results of combination chemotherapy and immunotherapy regimens containing interleukin-2 (biochemotherapy) are promising, and ongoing research will determine whether a survival impact will be confirmed in randomised studies. Vaccine therapy is another exciting area of research, and clinical trials are ongoing in both metastatic melanoma and as adjuvant therapy. A bewildering array of vaccines (whole cell, carbohydrate and peptide) is available, and it remains to be seen which of these numerous preparations will be most effective. Adjuvant therapy trials with a ganglioside GM2 vaccine and others are ongoing. Numerous peptide vaccines are also being investigated for metastatic melanoma, singly and in combination with other immunotherapeutic agents.