Secondary screening of platinum compounds in human ovarian cancer xenografts in nude mice.
Five TNO platinum compounds were evaluated for antitumor activities in two human ovarian carcinoma tumor lines grown in nude mice. The most active drug, TNO-38, was investigated in five additional lines with a known range of sensitivity to cisplatin. None of the new compounds showed superior activity to cisplatin. The slightly lower activity of TNO-38 as compared to the parent compound was reproducible in all tumor lines. Besides the similarity in the antitumor activity, a remarkable correspondence in platinum distribution and retention at 24 hr of TNO-38 and cisplatin could be observed. Chromatographic analysis of the compounds in their injection fluids showed single peaks for TNO-26 and TNO-38. The degradation products of the latter drugs may have affected their activity and toxicity. These human ovarian cancer xenografts may offer a reliable screening model for selection of a cisplatin analog with a higher therapeutic index or without cross-resistance for treatment in ovarian cancer.
D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D002945:Cisplatin / Q000378:metabolism / Q000627:therapeutic use; D005260:Female; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009944:Organoplatinum Compounds / Q000378:metabolism / Q000627:therapeutic use; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010984:Platinum / Q000378:metabolism / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D010984:Platinum; D002945:Cisplatin