Antitumor activity of a new platinum complex, 2-aminomethyl-pyrrolidine (1, 1-cyclobutanedicarboxylato) platinum (II).

One hundred cis-diamminedichloroplatinum (II) (CDDP) analogs have been evaluated for antitumor activity in male CDF1 mice subcutaneously (s.c.) implanted with tumor fragments of Colon 26 carcinoma. Among the complexes tested, 2-aminomethyl-pyrrolidine (1, 1-cyclobutanedicarboxylato) platinum (II) (DWA 2114) had the best antitumor effect. The mice intraperitoneally (i.p.) injected with DWA 2114 at a dose of 40 mg/kg/day on days 4, 6 and 8 after inoculation showed a 97% growth inhibitory ratio (GIR) on day 14 compared to the non-treated control mice. We evaluated the inhibitory effects of DWA 2114 on other tumors, such as Colon 38 carcinoma, Ca 755 mammary adenocarcinoma and L1210 leukemia, and found that it also had antitumor effects on various kinds of tumors. The nephrotoxicity-inducing activity of DWA 2114 and CDDP was evaluated in normal BDF1 mice, as indicated by changes in blood urea nitrogen (BUN) at almost the maximum tolerated dose (MTD) (DWA 2114: 100 mg/kg, CDDP: 12 mg/kg). DWA 2114 had no effect on BUN levels, while CDDP elevated BUN levels. These results indicate that DWA 2114 represents a second generation platinum antitumor complex.