The effects of ketoconazole on the human fibrosarcoma cell line HT-1080

In light of the reported cytotoxic effects of the antifungal agent ketoconazole on several malignant cell lines, we investigated the in vitro and in vivo effects of this drug on the human fibrosarcoma cell line HT-1080. Utilizing an anchorage dependent in vitro assay, we demonstrated an IC90 of 10.0 micrograms/ml at 72 hours and a decreasing IC90 with increasing exposure (IC90 = 6.2 micrograms/ml at 12 days). In vivo investigation utilizing the subcutaneous growth of this tumor in athymic mice and the oral, subcutaneous or intraperitoneal administration of ketoconazole at doses of 5-50 mg/kg/day demonstrated no consistent activity. Ketoconazole appears to have significant in vitro activity for HT-1080 but this does not translate into significant in vivo activity and its clinical relevance in sarcoma remains uncertain.