Comparative activity and distribution studies of five platinum analogues in nude mice bearing human ovarian carcinoma xenografts.
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.
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
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D002945:Cisplatin