[The prospect for cisplatin analogs from the experimental standpoint].
In the last decade a number of cisplatin analogs have been extensively synthesized to develop new Pt complexes with better antitumor activity and less nephrotoxicity than cisplatin. Antitumor Pt complexes consist of two carrier ligands and two or four leaving groups according to Pt valence. Our screening results of over 500 Pt complexes suggested that the carrier ligands influenced antitumor activity, especially the antitumor spectrum, while the leaving groups affected water solubility, stability, toxicity, and so forth. Recently, more than 10 cisplatin analogs have been clinically tested. In Japan four complexes have been evaluated in phase II. Most of them showed less nephrotoxicity than cisplatin. Instead, myelotoxicity was often observed. These complexes were significantly effective against various murine Their antitumor spectra, however, were somewhat different from each other. The Pt complexes such as cisplatin, carboplatin and 254-S, having the same carrier ligands, diammine, showed a quite similar spectrum. Sensitivity of cell lines derived from human tumors to these analogs were also examined in vivo and/or in vitro. So far as reported, their antitumor spectra were not so different from that of cisplatin. The cross-resistance patterns of cisplatin-resistant sublines to the complexes also depend on types of carrier ligands. Besides, L-1210/DDP showed cross-resistance only to a few carrier ligands, whereas P388/DDP did so to all of them tested. Thus, it might be a reasonable trial to search for a carrier ligand, the complexes of which would show a unique and broad antitumor spectrum including cisplatin-resistant lines and, in addition, not only against murine tumors but against human tumor cells.
Tashiro
T
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Cancer Chemotherapy Center, Japanese Foundation for Cancer Research.
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D018288:Carcinoma, Small Cell / Q000473:pathology; D055598:Chemical Phenomena; D002621:Chemistry; D002945:Cisplatin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D004337:Drug Carriers; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects; D007970:Leukopenia / Q000139:chemically induced; D008024:Ligands; D008175:Lung Neoplasms / Q000473:pathology; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D010051:Ovarian Neoplasms / Q000473:pathology; D051381:Rats; D013274:Stomach Neoplasms / Q000473:pathology; D013921:Thrombocytopenia / Q000139:chemically induced; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D004337:Drug Carriers; D008024:Ligands; D009944:Organoplatinum Compounds; D002945:Cisplatin