Platinum neurotoxicity: clinical profiles, experimental models and neuroprotective approaches.
This paper reviews the neurotoxic side-effects associated with platinum drugs, experimental approaches to studying this toxicity and attempts to use neuroprotective agents in conjunction with platinum drugs. Platinum drugs differ in their neurotoxicity profiles in patients. The frequency, severity, mode of onset and reversibility of peripheral nerve toxicity varies between different platinum analogues. Animal models, primary cultures of dorsal root ganglia neurons and tumour cell-lines of neuronal origin are being used in attempts to identify potential treatments for platinum-induced neurotoxicity. To date, clinical trials have been hampered by the poor tolerance of neuroprotective treatments and failure to achieve reversal of platinum drug neurotoxicity with thiols, neurotrophic factors or calcium channel blockers.
Screnci
D
D
Department of Pharmacology and Clinical Pharmacology, University of Auckland, New Zealand.
McKeage
M J
MJ
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000633:toxicity; D002121:Calcium Channel Blockers / Q000494:pharmacology; D016190:Carboplatin / Q000009:adverse effects / Q000633:toxicity; D002945:Cisplatin / Q000009:adverse effects / Q000633:toxicity; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000517:prevention & control*; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000633:toxicity; D000077150:Oxaliplatin; D017671:Platinum Compounds / Q000009:adverse effects* / Q000633:toxicity; D013438:Sulfhydryl Compounds / Q000494:pharmacology
D000970:Antineoplastic Agents; D002121:Calcium Channel Blockers; D018696:Neuroprotective Agents; D009944:Organoplatinum Compounds; D017671:Platinum Compounds; D013438:Sulfhydryl Compounds; D000077150:Oxaliplatin; D016190:Carboplatin; D002945:Cisplatin; C049777:ormaplatin