Antitumor Activity of Quinocarmycin (KW2152) against Various Cultured Leukemia and Lymphoma Cell Lines in Vitro1

Growth inhibitory activity of quinocarmycin citrate (KW2152) against 25 human cultured cell lines derived from leukemias and lymphomas was assessed quantitatively by regrowth assay. EC*>values (drug concentra tion required for 90% growth inhibition of treated cells) measured at l-h exposure to the drug in vitro were more than 16 «¿g/ml in five of six 1cell lines derived from T-lymphoma/leukemia, hence they were insensitive to KW2152. On the other hand, four of six B-cell lines derived from Blymphoma and three of four cell lines derived from non-T, non-B acute lymphoblastic leukemia were sensitive to KW2152 with EG»values of 0-3 to 2.2 jig/ml at l-h exposure. Six myelomonocytoid cell lines derived from acute myelogenous leukemia were also sensitive with EC«values of 1.8 to 3.0 /xg/ml on l-h exposure, but two myeloid cell lines derived from chronic myelogenous leukemia and one cell line derived from erythroleukemia were insensitive with KCw values of more than 16 /ig/ ml. The EGm values of most cell lines decreased as exposure time increased, and those measured at 24-h exposure were similarly low and mostly in the 0.02 to 0.06 /¿g/ml range. The kinetics analysis of growth inhibitory activity of KW2152 revealed that the drug showed timedependent action. These in vitro results, as correlated with in vivo results reported elsewhere (K. Fujimoto, T. Oka, and M. Morimoto, Cancer Res., 47:1516-1522,1987), suggest that daily consecutive or continuous dose therapy as well as single or intermittent large-dose therapy would be worthy of testing in the clinical trial of KW2152.