Chemotherapy and chemoimmunotherapy in disseminated malignant melanoma

Treatment of metastatic melanoma with cytotoxic drugs is still associated with low response rates and high toxicity. The most effective single agents in metastatic melanoma produce response rates between 15 and 20%. Combined schedules based on dacarbazine (DTIC), carmustine (BCNU), cisplatin and vinca alkaloids produced objective response rates between 25% and more than 40%; adverse effects, however, were severe and prolongation of survival remains uncertain. Cytokines were therefore introduced as melanoma treatment, with initial high expectations. Interferon (IFN)-alpha as a single treatment produced an overall response rate of 10-15% in melanoma patients. Clinical and experimental results suggest that the antitumour activity of IFN is mainly related to its antiproliferative effect; immunomodulatory effects were not substantiated in clinical investigations. Adoptive immunotherapy of metastatic melanoma has been established by use of lymphokine-activated killer (LAK) cells plus interleukin-2 (IL-2) or high dose IL-2 alone. Clinical trials of adoptive immunotherapy showed objective response rates of 20-25% in disseminated melanoma, and response rates could be further improved by the combination of IL-2 with IFN-alpha. Clinical trials with combined IFN or/and IL-2 and cytostatic drug therapy started a few years ago and have yielded promising initial results. The combination of IFN-alpha with dacarbazine was effective in over 50% of treated patients, leading to complete or partial remissions in 28% and stabilization of the disease in an additional 28% of more than 400 patients treated so far. Recently, a new generation of multidrug combinations including IFN-alpha and/or IL-2 has been initiated with overall response rates of more than 50% in several reports.(ABSTRACT TRUNCATED AT 250 WORDS)