Antitumor activity of quinocarmycin (KW2152) against various cultured leukemia and lymphoma cell lines in vitro.

Growth inhibitory activity of quinocarmycin citrate (KW2152) against 25 human cultured cell lines derived from leukemias and lymphomas was assessed quantitatively by regrowth assay. EC90 values (drug concentration required for 90% growth inhibition of treated cells) measured at 1-h exposure to the drug in vitro were more than 16 micrograms/ml in five of six T-cell lines derived from T-lymphoma/leukemia, hence they were insensitive to KW2152. On the other hand, four of six B-cell lines derived from B-lymphoma and three of four cell lines derived from non-T, non-B acute lymphoblastic leukemia were sensitive to KW2152 with EC90 values of 0.3 to 2.2 micrograms/ml at 1-h exposure. Six myelomonocytoid cell lines derived from acute myelogenous leukemia were also sensitive with EC90 values of 1.8 to 3.0 micrograms/ml on 1-h exposure, but two myeloid cell lines derived from chronic myelogenous leukemia and one cell line derived from erythroleukemia were insensitive with EC90 values of more than 16 micrograms/ml. The EC90 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 micrograms/ml range. The kinetics analysis of growth inhibitory activity of KW2152 revealed that the drug showed time-dependent 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.