Phase II Trial of a Combination of Interferon-βserand Interferon-γ in Patients with Advanced Malignant Melanoma

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Abstract
Based upon the in vitro synergistic activity of interferon-.beta. (IFN-.beta.) and interferon-.gamma. (IFN-.gamma.) observed in melanoma cells, we initiated a Phase II trial sing the combination to determine the clinical antitumor efficacy in patients with advanced disease. Fifteen patients with metastatic malignant melanoma were given 2,000 .mu.g of recombinant IFN-.gamma. (rIFN-.gamma.) (Biogen) intravenously (i.v.) over 10 min, followed by a 10 min i.v. injection of 30 million units of recombinant IFN-.beta. (rIFN-.beta.ser) (Triton) 3.times./week. Six patients had skin, soft tissue, nodal, or subcutaneous metastases, 6 had visceral disease only, and 3 had both. Seven patients had received prior treatment, including chemotherapy (6), radiotherapy (3), and/or immunotherapy (3). Side effects included typical IFN constitutional symptoms such as anorexia, fatigue, nausea, and myalgias, but were not dose limiting. The mean drop in the whte blood cell count (WBC) following 1 month of therapy, compared to baseline, was 3.3 .times. 103/mm2 (p = 0.002); the mean increase in SGOT was 24.1 U/l (p < 0.001). One patient had a dose reduction for Grade III anorexia and fatigue which did not resolve with repeated treatment. One patient with liver metastases had radiographical and clinical stabilizatoin of his disease for 1 year. No responses were seen. The mean time to progression weas 6 weeks. Two patients'' tumors were evaluable in the human tumor colony forming assay (HTCFA) and were markedly sensitive to the antiproliferative effects of IFN combinations. Both patients, however, fialed to respond clinically. We conclude that the combination of IFN-.gamma. and IFN-.beta.ser, when administered by this dose and schedule, was well tolerated but not effective in metastatic malignant melanoma.