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Comparative Activity and Distribution Studies of Five Platinum Analogues in Nude Mice Bearing Human Ovarian Carcinoma Xenografts¹

Free University Hospital, Department of Oncology [E. B., R. N., H. S., H. M. P.], and Research Laboratory of Internal Medicine [W. J. F. V.], De Boelelaan 1117, 1007 MB Amsterdam, The Netherlands

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.

¹ This work was supported by Netherlands Cancer Foundation Grant AUKC 82-7.

² To whom requests for reprints should be addressed.

Received 9/27/83. Accepted 9/11/84.

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