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Abstract
A novel anti-tumor platinum(IV) complex, coded as LA-12, with a bulky adamantylamine ligand displaying oral activity was prepared and its oral activity was evaluated. The murine ADJ/PC6 plasmacytoma and human A2780 ovarian carcinoma tumor model were used to evaluate the in vivo anti-tumor activity of a single dose and also of repeated doses with comparison to the activity of cisplatin and of the platinum(IV) complex satraplatin. The acute toxicity of LA-12 in mice is relatively low (maximum tolerated dose 1000 mg/kg), and the effective dose is comparable to that of cisplatin and higher than that of satraplatin. The therapeutic index derived from this is very high (250). In the human tumor model, two repeated dose schedule regimens were evaluated. LA-12 exerted a significantly higher anti-tumor activity than other substances, i.e. cisplatin and satraplatin, in repeated doses on the murine ADJ/PC6 plasmacytoma tumor model. The dailyx5 repeated dose regimen was selected for further evaluation.
Published Version
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