Histology and platinum content of sensory ganglia and sural nerves in patients treated with cisplatin and carboplatin: an autopsy study

Abstract

Cisplatin is a valuable antineoplastic drug which as a dose-limiting side-effect causes sensory neuropathy, and which therefore is often combined with less neurotoxic carboplatin. It has not been possible to reproduce cisplatin neuropathy in experimental animals, and the neurotoxic mechanism in man is disputed. We investigated post-mortem material from 12 patients and 15 control subjects. Half of the fibres with diameters of > or = 9 microns, or more than 15% of all fibres (P < 0.02), had disappeared in the sural nerves of patients. Signs of axonal regeneration were lacking. The dorsal root ganglia D12 and L2 of some but not of all patients contained necrotic neurons and nodules of Nageotte. The mean volume of the somata was reduced by 18% (P < 0.03). A relation between cumulated doses, treatment free interval and changes in nerve or ganglia was not found. The platinum content was high in all tissues except in the spinal cord when the patient had died shortly after treatment, and it decreased with increasing interval, least so in liver, sensory ganglia and sural nerves. The results support the hypothesis that cisplatin neuropathy is a neuroneopathy rather than a dying-back axonopathy.

Renal Toxicity Associated with Weekly Cisplatin and Gemcitabine Combination Therapy for Treatment of Advanced Biliary Tract Cancer

“…Generally, cisplatin is concentrated at higher levels in the dorsal root ganglion cells and causes apoptosis of sensory neurons [42,43]. Various attempts have been reported to reduce the neuropathy associated with cisplatin, and some agents have been reported to be promising for neuroprotection [44,45].…”

Post-chemotherapy neuropathy

“…Dorsal root ganglion, for being less protected by the nervous-blood barrier, is more vulnerable to neurotoxicity. This explains the predominance of sensory manifestation is patients affected by neuropathy 12,13 . A common finding in nervous conduction studies is a sensory axonal injury with decreased action potentials amplitude, which may result from more complex cell changes resulting from mitochondrial alterations 14 , interference with microtubules; qualitative neuronal membrane changes, oxidative stress 15 and neuronal apoptosis 16 .…”

Selenium protects cerebral cells by cisplatin induced neurotoxicity

“…Cisplatin neurotoxicity including ototoxicity, peripheral sensory polyneuropathy and focal encephalopathy are among the most important dose limiting toxicities 15,16 . Many previous studies have focused on the neurotoxicity of cisplatin in peripheral neuropathy and effectiveness of chemo protective agents 6,18,25,26 . Only a few studies have focused on central neurotoxicity of cisplatin 13,27,28 .…”