ANTITUMOR-ACTIVITY OF INOMETHYL)-2-ISOPROPYL-1,3-DIOXOLANE]PLATINUM(II), A NEW PLATINUM ANALOG, AS AN ANTICANCER AGENT

The in vitro and in vivo antitumor activity of a new antitumor platinu m complex, cis-malonato[(4R, 5R)-4, aminomethyl)-2isopropyl-1,3-dioxol ane]platinum(II) (SKI 2053R, NSC D644598), were evaluated and compared with those of cisplatin (CDDP) and carboplatin (CBDCA) using murine t umors. SKI 2053R was highly active in vitro against both L1210 murine leukemia and its CDDP-resistant subline, L1210/DDP; the relative resis tances were 20.0-, 14.5-, and 2.7-fold for CDDP, CBDCA, and SKI 2053R, respectively. SKI 2053R showed activity comparable with or superior t o either CDDP or CBDCA in mice implanted with L1210. In mice implanted with L1210/DDP, as compared with CBDCA, SKI 2053R showed high values for the percentage of treated survivors relative to controls and for n umbers of cured mice, whereas CDDP had virtually no activity. In mice implanted with P388, all three drugs were highly active, but the inten sity of activity was shown to be ranked in the following order: SKI 20 53R > CDDP > CBDCA. The antitumor activity of SKI 2053R against Lewis lung carcinoma was comparable with that of both CDDP and CBDCA. The an titumor activity of SKI 2053R was further investigated against two hum an tumor xenografts, KATO III (stomach adenocarcinoma) and WiDr (colon adenocarcinoma), implanted s.c. in nude mice and was compared with th at of CDDP. In SKI 2053R-treated groups, the time required for a mean tumor weight of 1,000 mg was 33.1 days in KATO III xenografts and 35.0 days in WiDr xenografts as compared with 30.2 and 27.2 days in CDDP-t reated groups, respectively. SKI 2053R achieved growth-inhibition rate s comparable with those of CDDP against KATO III(65% versus 59%) and W iDr xenografts (64% versus 54%) on day 35. These results indicate that SKI 2053R is an attractive candidate for further development as a cli nically useful anticancer drug.