In vitro and in vivo activity of two second generation platinum analogs in murine bladder cancer

The activity of cis-diamminedichloroplatinum(II) was compared to two second generation platinum analogs, cis-diammine-1,1-cyclobutane dicarboxylate platinum(II) and cis-dichlorotransdihydroxybisisopropylamine platinum(IV) in the N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide-induced murine bladder tumor model and a tumor colony assay. Murine drug testing revealed that all three drugs were active against the MBT-2 tumor line, although cis-diamminedichloroplatinum(II) was more active than its analogs. All drugs produced enhanced inhibition of clonal growth with increasing drug exposure times. Cis-diamminedichloroplatinum(II) was more active against MBT-2 cells in the plateau growth phase versus the log growth phase after a one hour drug exposure. Similar differential activity depending upon the proliferative state of MBT-2 was not seen with the two platinum analogs. These two platinum analogs have somewhat less activity in vivo and in vitro than cis-diamminedichloroplatinum(II) and would be predicted to be less effective clinically in human bladder cancer than the parent compound.