Comparative activity and distribution studies of five platinum analogues in nude mice bearing human ovarian carcinoma xenografts
Boven, E.; van der Vijgh, W.J.; Nauta, M.M.; Schlüper, H.M.; Pinedo, H.M.
Cancer Research 45(1): 86-90
1985
ISSN/ISBN: 0008-5472 PMID: 4038381 Document Number: 257176
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.