A strategy for the development of two clinically active cisplatin analogs: CBDCA and CHIP.
The antitumor agent cisplatin has a broad antitumor spectrum and has been incorporated into regimens that are curative for some malignant diseases. However, one of the major limitations to its clinical usefulness is the incidence of severe toxicities involving several major organ systems. Therefore, much enthusiasm has been generated for the development of cisplatin analogs that demonstrate an improved therapeutic index in some preclinical models. The two most promising analogs are CBDCA (carboplatin) and CHIP (iproplatin). The preclinical and early clinical trial results have demonstrated that these two compounds show activity in cisplatin-responsive tumors. The preclinical background providing the rationale for the clinical development of these two analogs is described. We suggest a means of screening for each analog's clinical antitumor activity and determining the analogs' utility against specific malignant diseases compared with that of the parent compound or standard treatment.
Foster
B J
BJ
Investigational Drug Branch, National Cancer Institute, Bethesda, Maryland.
Harding
B J
BJ
Wolpert-DeFilippes
M K
MK
Rubinstein
L Y
LY
Clagett-Carr
K
K
Leyland-Jones
B
B
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016190:Carboplatin; D055598:Chemical Phenomena; D002621:Chemistry; D002945:Cisplatin / Q000031:analogs & derivatives*; D015195:Drug Design; D004341:Drug Evaluation; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007939:Leukemia L1210 / Q000188:drug therapy; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011916:Rats, Inbred F344
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C023359:iproplatin; D016190:Carboplatin; D002945:Cisplatin