Lack of neurotoxicity of oral bisacetatoamminedichlorocyclohexylamine-platinum(IV) in comparison to cisplatin and tetraplatin in the rat.
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 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. Bisacetatoamminedichlorocyclohexylamineplatinum(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.
McKeage
M J
MJ
Drug Development Section, Institute of Cancer Research, Belmont, Sutton, Surrey, United Kingdom.
Boxall
F E
FE
Jones
M
M
Harrap
K R
KR
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007274:Injections, Intraperitoneal; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000503:physiopathology; D009431:Neural Conduction / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D009944:Organoplatinum Compounds / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C081294:satraplatin; D002945:Cisplatin; C049777:ormaplatin