Quinocarmycin monicitrate (KW2152) and its analogue,
DX-52-1, demonstrated specificity for
melanomas in the National Cancer Institute in vitro human tumor cell line
drug screen. In contrast to most cell lines, a 50% reduction in
tumor cell burden (as measured
protein) at the end of a 48-h
drug incubation was produced in five of eight
melanoma lines by KW2152 concentrations (LC50s) ranging from 0.49 to 10.93 microM and by
DX-52-1 concentrations ranging from 0.71 to 7.33 microM. Using the COMPARE algorithm, the patterns of differential cytotoxicity for both agents at the LC50 level of effect most closely resembled those for
actinomycin D,
mithramycin, and
Adriamycin. In in vivo studies, both KW2152 (40 mg/kg/day) and
DX-52-1 (90 mg/kg/day) caused partial and complete regressions of staged s.c.-implanted LOX IMVI
melanoma xenografts following i.p. administration on days 5, 9, and 13 and produced
tumor growth delays of 231 and 181%, respectively (P < 0.001). Activity 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 every fourth or seventh day i.p. treatments. Based on these findings,
DX-52-1 has been selected by the National Cancer Institute for development to clinical trial especially against
melanomas. This agent represents one of the first to be selected for preclinical development based on disease-panel specificity discovered in the National Cancer Institute
cancer drug screen.