The in vitro and in vivo antitumor activity of a new antitumor
platinum complex, cis-malonato[(4R, 5R)-4,5- bis(aminomethyl)-2-isopropyl-1,3-
dioxolane]
platinum(II) (SKI2053R, NSC D644591), were evaluated and compared with those of
cisplatin (CDDP) and
carboplatin (
CBDCA) using murine
tumors.
SKI 2053R was highly active in vitro against both L1210 murine
leukemia and its CDDP-resistant subline, L1210/DDP; the relative resistances were 20.0-, 14.5-, and 2.7-fold for CDDP,
CBDCA, and
SKI 2053R, respectively.
SKI 2053R showed activity comparable with or superior to 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 numbers of cured mice, whereas CDDP had virtually no activity. In mice implanted with P388, all three drugs were highly active, but the intensity of activity was shown to be ranked in the following order:
SKI 2053R > CDDP >
CBDCA. The antitumor activity of
SKI 2053R against
Lewis lung carcinoma was comparable with that of both CDDP and
CBDCA. The antitumor activity of
SKI 2053R was further investigated against two human
tumor xenografts, KATO III (stomach
adenocarcinoma) and WiDr (
colon adenocarcinoma), implanted s.c. in nude mice and was compared with that 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-treated groups, respectively.
SKI 2053R achieved growth-inhibition rates comparable with those of CDDP against KATO III (65% versus 59%) and WiDr xenografts (64% versus 54%) on day 35. These results indicate that
SKI 2053R is an attractive candidate for further development as a clinically useful anticancer
drug.