title: Comparative activity and distribution studies of five platinum analogues in nude mice bearing human ovarian carcinoma xenografts.
abstract: The antitumor activity of four new platinum analogues was compared at equitoxic doses to that of cisplatin in B10 LP/cpb nude mice bearing xenografts of human ovarian carcinomas. The two tumor lines used, MRI-H-207 and Pe, differ in histology, tumor doubling time, and sensitivity to cisplatin. Complete remission of MRI-H-207 was observed with cisplatin, carboplatin, iproplatin, and JM-40, while spiroplatin only gave growth delay. Cisplatin and carboplatin caused some growth delay of Pe, while JM-40, spiroplatin, and iproplatin failed to affect tumor growth. Platinum tissue distribution was also measured for each compound in groups of five to seven tumor-bearing mice. Platinum concentrations in the two tumors at 24 hr were similar for cisplatin and carboplatin, but differed for iproplatin, spiroplatin, and JM-40. Organ distribution was similar for each analogue, and concentrations were significantly higher in kidneys than in liver, except for iproplatin with comparable concentrations in these organs. Our findings show a good correlation between analogue activity in ovarian cancer in the clinic and that in MRI-H-207. Platinum concentrations in tumor tissue did not predict antitumor activity.
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002460:Cell Line; D002945:Cisplatin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D005260:Female; D007700:Kinetics; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D013329:Structure-Activity Relationship; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D002945:Cisplatin