Comparative cytotoxicity between cisplatin and second generation platinum analogs

The cytotoxic activity of cis-DDP and four second generation platinum coordination complexes (TNO-6; JM-82; JM-8; and JM-9) was compared on six established human colon carcinoma cell lines with different degrees of differentiation. Cytotoxicity was evaluated by the inhibition of colony formation technique. Cis-DDP was uniformily active against all lines. JM-8 and JM-9 were virtually ineffective for all cell lines, even at concentrations as high as 50 micrograms/ml. JM-82 was slightly more active although (with the exception of LoVo cells) still about 10-fold less efficacious than cis-DDP. TNO-6 was the only derivative with appreciable cytotoxic activity although about 2 to 5-fold less than cis-DDP for lines SW48, 620, 480, and 1116. For LoVo and SW403, TNO-6 was slightly more active than cis-DDP. In both such instances, increased efficacy resulted from abrogation of the shoulder region of the survival curve while the slope remained essentially intact. Thus any enhancement in therapeutic efficacy with these second generation analogues can only be expected from possible decreases in toxic effects but not from superior tumor cell kill activity.