Perspectives of cytokine treatment in malignant skin tumors.

Cytokines have been tested in the treatment of different skin cancers during the last decade, and treatment schedules have been established or proposed for several malignant skin tumors. Preferentially, the interferons and interleukin-2 were found to be effective in treating skin cancers. Interferons alpha and beta have been approved for the treatment of human immunodeficiency virus (HIV)-associated Kaposi's sarcoma, cutaneous T cell lymphoma, and malignant melanoma in several countries. Interferon alpha was found to be most effective in cutaneous T cell lymphoma with 40%-60% overall responses. When combining interferon alpha with psoralens and ultraviolet A (PUVA) or with retinoids, even higher response rates up to 60%-90% were reported, and long-term remissions have been described. A considerable activity of interferon alpha was found in HIV-associated Kaposi's sarcoma with response rates of 30%-50%. The effectiveness of Kaposi's sarcoma's treatment was further improved by combining interferon alpha and zidovudine. Responses to interferon alpha in metastatic malignant melanoma are rather seldom (10%-15%), but a stabilization of the disease with prolonged survival was reported after interferon alpha treatment. Additionally, interleukin-2 was found to be active in metastatic melanoma, with overall response rates of about 20%, and both biological agents were found to have an additive efficacy in combination. Several combined regimens of interferon alpha, interleukin-2, and polychemotherapy have been described in metastatic melanoma, and overall response rates higher than 50% were found with these combined treatment modalities. Interferon alpha and beta were also intralesionally injected into basal cell carcinomas and other epithelial skin cancers, and complete responses were found in more than 80% of tumors treated. Local applications of interferons and interleukin-2 were likewise found to be effective in the treatment of cutaneous melanoma metastases and cutaneous manifestations of Kaposi's sarcoma. Cytokines and their combination with other treatment modalities has greatly enriched the treatment facilities in malignant skin tumors during recent years, and additional new cytokines will be introduced in skin cancer treatment in near future.