The antitumour activity of a series of ten novel ammine/amine platinum (IV) dicarboxylates of general formula [Pt(IV) Cl2 (OCOR1) NH3 (RNH2)] where R1 was an aliphatic or aromatic substituent and R an aliphatic or alicyclic substituent, was evaluated, after oral administration, to nude mice bearing various human ovarian carcinoma xenografts. The tumours were chosen to encompass a wide range in responsiveness to the clinically used platinum-based drugs cisplatin and carboplatin, with tumour growth delays varying from less than 10 days to greater than 60 days. Against two tumour lines, the platinum (IV) ammine/amine dicarboxylate JM221 (R1=C3H7; R= cC6H11) exhibited similar antitumour activity whether administered by the oral or intraperitoneal route. Experiments have been performed using four xenografts to provide a direct comparison of the antitumour effects of three platinum (IV) ammine/amine butyrates (JM216, R=cC6H11; JM225, R=cC5H9; JM269, R=cC7H13; R1=C3H7 for all three) administered by the oral route versus cisplatin and carboplatin administered by the intravenous route at equitoxic q7dx4 schedules. All three dicarboxylates exhibited oral activity broadly comparable to cisplatin and carboplatin and significantly superior to tetraplatin (Ormaplatin; a 1,2 diaminocyclohexane-containing platinum drug currently undergoing clinical evaluation). Average specific growth delay values across the four xenografted lines were 3.45 for cisplatin, 3.9 for carboplatin, 3.2 for JM216, 3.3 for JM225, 3 for JM269 and only 0.55 for tetraplatin. Thus the ammine/amine platinum (IV) dicarboxylates represent a novel class of platinum drug for oral administration capable of exhibiting broadly comparable activity to cisplatin and carboplatin in a panel of human ovarian carcinoma xenografts.

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