[Antitumor activity of a new platinum complex, (R)-(-)-2-aminomethylpyrrolidine (1, 1-cyclobutanedicarboxylato) platinum (II), against cisdiamminedichloroplatinum (II)-resistant murine leukemia cell line].
Antitumor activity of a new platinum complex, (R)-(-)-2-aminomethylpyrrolidine (1, 1-cyclobutanedicarboxylato) platinum (II) (DWA 2114 R) against cisdiamminedichloroplatinum (II) (CDDP)-resistant tumor was examined in in vitro and in vivo experiments. CDDP-resistant line was established from L 1210 mouse leukemia cells by continuous exposure to CDDP in dose-escalation manner. Six clones were isolated from parental resistant line and one of these clones, clone f, which was found to be highly resistant (30-40 fold) to CDDP, was used in the following experiments. Clone f showed 4-7 fold cross-resistance to DWA 2114 R and 11-19 fold to cisdiammine-1, 1-cyclobutanedicarboxylatoplatinum (II) (CBDCA) in in vitro growth inhibition assay. DWA 2114 R showed the most effective antitumor activity against mice transplanted with the resistant cells in the increase of life span (ILS%). About 100% of ILS and cured mice were observed in the treatment with DWA 2114 R. On the other hand, CDDP or CBDCA showed a little increase in the survival time (less than 40% of ILS) and all mice died. These results suggest that DWA 2114 R seemed to be more effective against CDDP-resistant tumors clinically than CDDP and CBDCA.
Exploratory Research Laboratories, Chugai Pharmaceutical Co. Ltd., Gotemba.
K
K
Akamatsu
K
K
Endo
T
T
Matsumoto
K
K
Kamisango
K
K
Morikawa
M
M
Koizumi
H
H
Mitsui
K
K
Koizumi
T
T
Matsuno
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016190:Carboplatin / Q000031:analogs & derivatives; D002460:Cell Line; D002945:Cisplatin / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D004351:Drug Resistance; D066298:In Vitro Techniques; D007939:Leukemia L1210 / Q000188:drug therapy*; D051379:Mice; D009368:Neoplasm Transplantation; D009944:Organoplatinum Compounds / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C058816:DWA 2114; D016190:Carboplatin; D002945:Cisplatin