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Lack of Neurotoxicity of Oral Bisacetatoamminedichlorocyclohexylamine-platinum(IV) in Comparison to Cisplatin and Tetraplatin in the Rat¹

Drug Development Section, The Institute of Cancer Research, Block E, 15 Cotswold Road, Belmont, Sutton, Surrey SM2 5NG United Kingdom

This study compared the effect on sensory nerve conduction velocity in the hind limb of chronically treated age-matched rats of a novel lipophilic p.o. platinum complex [bisacetatoamminedichlorocyclohexylamine-platinum(IV)], with that of the neurotoxic platinum complexes cisplatin and tetraplatin. Tetraplatin (i.p.) first caused slowing of sensory nerve conduction (-14.4% of controls; P < 0.05) at a dose (1 mg/kg) that was free of constitutional toxicity. Cisplatin (i.p.) first caused slowing of sensory nerve conduction (-17.5% of control; P < 0.05) at a dose (2 mg/kg) approximating the maximal tolerated dose. Bisacetatoamminedichlorocy-clohexylamineplatinum(IV) (p.o.) showed no slowing of sensory nerve conduction either after 20.5 weeks of treatment at a dose (25 mg/kg) approximating the maximal tolerated dose or after 6 weeks of treatment at a dose (50 mg/kg) which eventually proved intolerable. In conclusion, p.o. bisacetatoamminedichlorocyclohexylamineplatinum(IV) shows a lack of neurotoxicity compared to parenterally administered cisplatin and tetraplatin at the maximal tolerated dose in rats.

¹ This work was supported by grants to the Institute of Cancer Research by the Cancer Research Campaign (UK), the Medical Research Council, The Johnson Matthey Technology Centre, and Bristol Myers Squibb Oncology.

² To whom requests for reprints should be addressed, at Institute of Oncology, The Prince of Wales Hospital, High Street, Randwick, Sydney New South Wales 2031, Australia.

Received 11/ 3/93. Accepted 12/15/93.

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