Preclinical antitumor activity of CI-973,[SP-4-3-(R)]-[1,1- cyclobutanedicarboxylato(2-)](2 methyl-1,4-butane-diamine-N,N')platinum.
The antitumor activity of [SP-4-3-(R)]-[1,1-cyclobutanedicarboxylato-(2-)](2 methyl-1,4-butanediamine-N,N')platinum (CI-973) was characterized in a number of preclinical model systems. CI-973 retained substantial activity in cisplatin resistant murine leukemia cell lines, in vitro and in vivo; in L1210 leukemia resistant to cisplatin in vivo, CI-973 retained as much activity as was found in animals bearing sensitive L1210 leukemia. When compared in five solid murine tumors in vivo, both CI-973 and cisplatin were approximately equivalent in activity. In one human colon tumor and one human non-small cell lung carcinoma tested as xenografts in immunodeficient mice, cisplatin and CI-973 were ineffective. In two other human non-small cell lung carcinomas tested in the same fashion, cisplatin did possess activity. CI-973 has entered phase I clinical trials.
Kraker
A J
AJ
Cancer Research Section, Parke-Davis Pharmaceutical, Research Division Warner-Lambert Company, Ann Arbor, MI 48105.
Moore
C W
CW
Roberts
B J
BJ
Leopold
W R
WR
Elliott
W L
WL
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016190:Carboplatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007942:Leukemia, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; C055425:NK 121; D016190:Carboplatin; D002945:Cisplatin