EFFICACY OF THE QUINOCARMYCINS KW2152 AND DX-52-1 AGAINST HUMAN-MELANOMA LINES GROWING IN CULTURE AND IN MICE

Quinocarmycin monocitrate (KW2152) and its analogue, DX-52-1, demonstr ated specificity for melanomas in the National Cancer Institute in vit ro human tumor cell Line drug screen. In contrast to most cell lines, a 50% I eduction in tumor cell burden (as measured protein) at the end of a 48-h drug incubation was produced in five of eight melanoma line s by KW2152 concentrations (LC(50)s) ranging from 0.49 to 10.93 mu M I and by DX-52-1 concentrations ranging from 0.71 to 7.33 mu M. Using t he COMPARE algorithm, the patterns of differential cytotoxicity for bo th agents at the LC(50) level. of effect most closely resembled those for actinomycin D, mithramycin, and Adriamycin. In ill vivo studies, b oth KW2152 (40 mg/kg/day) and DX-52-1 (90 mg/kg/day) caused partial an d complete regressions of staged s.c.-implanted LOX IMVI melanoma xeno grafts following i.p. administration on days 5, 9, and 13 and produced tumor growth delays of 231 and 181%, respectively (P < 0.001). Activi ty was augmented by more prolonged therapy. Statistically significant growth inhibition of SK-MEL-2, UACC-62, UACC-257, and M14, but not SK- MEL-5 and MALME-3M, melanoma xenografts also was observed following ev ery fourth or seventh day i.p. treatments. Based on these findings, DX -52-1 has been selected by the National Cancer institute for developme nt to clinical trial especially against melanomas. This agent represen ts one of the first to be selected for preclinical development based o n disease-panel specificity discovered in the National Cancer Institut e cancer drug screen.