We compared the antitumor activity of cis-diamminedichloroplatinum(II) (cisplatin; CDDP) with three CDDP analogues: cis-diammine-1,1-cyclobutanedicarboxylateplatinum(II) (CBDCA), N-methyliminodiacetato-1,2-diamino(cyclohexane)platinum(II) (MIDP), and N-(2-hydroxyethyl)-iminodiacetato-1,2-diamino(cyclohexane)platinum(II) (HIDP). Fresh human tumor samples in the adhesive tumor culture system were utilized for this comparison. The equitoxic concentrations of all four drugs were derived based on their inhibitory activity against human bone marrow samples. For these normalized concentrations, CDDP proved to have a higher cytotoxic activity than its analogues. CBDCA's in vitro activity had a significant correlation with CDDP activity (r = 0.67) in vitro. However, the structurally similar substances MIDP and HIDP demonstrated a much greater degree of association (r = 0.90). Our data suggest that CBDCA, HIDP, and MIDP have overall less activity than CDDP when tested at equitoxic in vitro concentrations. Close association between CDDP and CBDCA also reflects known clinical experience with these two drugs, suggesting the method of comparison used here is probably appropriate. These conclusions, however, must be validated by clinical trials.
This study was supported in part by a contract JMV:bg 11783 from LifeTrac, Irvine, CA, by allotments from the Susan G. Komen Foundation, and from Physicians' Referral Service to Gary Spitzer; and by a grant from the National Cancer Institute RO1-CA41581 to Abdul R. Khokhar. These data were presented in part at the 78th Annual Meeting of the American Association for Cancer Research, Atlanta, GA; May 20–23, 1987.