Significant activity of a novel cytotoxic agent, LY295501, against a wide range of tumors in the human tumor cloning system

The diarylsulfonylureas (DSUs) are a novel class of cytotoxic agents with h igh potential for activity. LY295501 is one of the most active DSUs, In thi s study, we evaluated the cytotoxicity of LY295501 utilizing the human tumo r cloning assay, LY295501 was tested at 10, 50 and 100 mu g/ml using either Ih or continuous exposure schedules. The majority of common solid tumors w ere evaluated including breast, colorectal, non-small cell lung and ovarian carcinomas. LY295501 demonstrated significant activity against all tumor t ypes tested. Antitumor activity was noted after either 1 h or continuous ex posure schedules at all concentrations tested. A concentration-response rel ationship was noted, with increasing concentrations of LY295501 leading to more cytotoxicity. Cytotoxicity, on the continuous exposure schedule, was n oted in 38% of tumors exposed to LY295501 at 10 mu g/ml, 58% of tumors expo sed at 50 mu g/ml (p=0.002 for 10 versus 50 mu g/ml) and 72% of tumors expo sed at 100 mu g/ml (p=0.008 for 50 versus 100 mu g/ml). In addition, more c ytotoxicity was observed on the continuous exposure schedule compared to th e 1 h schedule at all concentrations tested (p<0.01). The substantial activ ity of LY295501 in the human tumor cloning assay coupled with its clinical activity in phase I studies supports further clinical development of this a gent. [(C) 1999 Lippincott Williams & Wilkins.]