[Preclinical and clinical evaluation of toxicity and antitumor activity of cisplatin analogues].
Since the introduction of Cisplatin (CDDP) into clinical practice in 1972, CDDP has assumed an important role in the treatment of various tumors. But its renal toxicity has been proved to be a dose limiting factor. Thus the total number of courses which may be given is limited. For this reason, efforts have been made to develop CDDP analogues with reduced toxicities, especially renal toxicity, and more enhanced antitumor activity, and they are now reaching the clinical testing phase. Among them Carboplatin (CBDCA), 254-S, DWA 2114R and NK 121 have been well studied. These analogues were noted to be less nephrotoxic, but more myelosuppressive than CDDP in preclinical analysis. As for cytotoxicity, their inhibitory effects on tumor growth in murine experimental system were similar or more to that of CDDP. Due to these data clinical trials have been carried out. Phase I studies have shown that these analogues are relatively free of renal toxicity as evaluated in preclinical studies and that their dose limiting factor is myelosuppression. Estimation of cross resistance to CDDP and antitumor spectrum have been studied at phase II trials which are ongoing. Interim reports have not shown that enhanced tumor activity or enlarged antitumor spectrum are expected.
Ariyoshi
Y
Y
Dept. of Medicine, Aichi Cancer Center, Nagoya, Japan.
Ota
K
K
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001853:Bone Marrow / Q000187:drug effects; D016190:Carboplatin / Q000031:analogs & derivatives; D002945:Cisplatin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004341:Drug Evaluation; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007668:Kidney / Q000187:drug effects; D007970:Leukopenia / Q000139:chemically induced; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy; D009374:Neoplasms, Experimental / Q000188:drug therapy; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000139:chemically induced
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C058816:DWA 2114; C055425:NK 121; C053989:nedaplatin; D016190:Carboplatin; D002945:Cisplatin