COMBINATION THERAPY WITH INTERFERON-GAMMA AND INTERLEUKIN-2 FOR THE TREATMENT OF METASTATIC MELANOMA

The toxicity and clinical response to treatment with the combination o f interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) in patients wi th metastatic melanoma was evaluated. From May 1993 through February 1 994, 20 patients were treated with 24 courses of IFN-gamma with or wit hout IL-2, A 7-day course of subcutaneous IFN-gamma alone was administ ered to cohorts of two or three patients each at doses of 0.1, 0.2, or 0.3 mg/m(2). Thirteen patients received escalating doses of IFN-gamma between 0.2 and 0.5 mg/m(2) followed by the intravenous (i.v.) admini stration of IL-2 (720,000 IU/kg) given three times a day. A treatment course consisted of two cycles (maximum of 15 doses of IL-2 per cycle) separated by a 10-day interval, Five additional patients were treated with five courses of IFN-gamma, IL-2, and tumor-infiltrating lymphocy tes (TILs). All patients treated had the diagnosis of metastatic melan oma. The maximal tolerated dose of subcutaneous IFN-gamma was establis hed at 0.3 mg/m(2) with dose-limiting hepatotoxicity. Immunohistochemi stry analyses showed detectable upregulation of MHC class I alleles in one (8%) of 12 patients. Two of 20 patients who received the combinat ion of IFN-gamma and IL-2 had responses, one partial and one complete response. The duration of response was 7 months for the partial respon se and 12 months for the complete response. IFN-gamma was tolerated wi th minimal side effects of nausea, vomiting, malaise, and decreased he matopoiesis. No increased toxicities were found with the combination t reatment, as compared with IL-2 alone. One death occurred on the third day of treatment with IFN-gamma alone from hemorrhage into brain meta stases. There were no responders in the five patients who received the combination treatment of TIL, IL-2, and IFN-gamma. From these finding s, we conclude that further studies looking at this combination treatm ent are not warranted.