Cisplatin neurotoxicity: the relationship between dosage, time, and platinum concentration in neurologic tissues, and morphologic evidence of toxicity.

PURPOSETo identify the major sites of platinum accumulation within neural tissues after treatment with cisplatin and to determine the relationship between cumulative dosage, time, and the development of histopathological and clinical neurotoxicity.PATIENTS AND METHODSTwenty-one patients treated antemortem with cisplatin had neural tissue harvested at autopsy. Neural tissues were assayed for platinum and examined for histopathologic evidence of neurotoxicity. The relationship between histopathologic neurotoxicity and various pharmacologic parameters was analyzed.RESULTSTissue platinum levels were found to be highest in the dorsal root ganglia and lowest in tissue protected by the blood-brain barrier. For peripheral nerve, dorsal root, and dorsal root ganglia, a linear relationship was observed between platinum levels and cumulative dose. Platinum levels in neural tissue were not observed to decrease with time. Histopathologic toxicity closely matched an index of exposure to platinum (cumulative dose and lo...