An Update on Toxic and Drug-Induced Peripheral Neuropathies
An Update on Toxic and Drug-Induced Peripheral Neuropathies
There are no real breakthroughs for the treatment of CIPN. Data from an experimental animal model completed by a randomized controlled trial in patients with nonsmall cell lung cancer treated with cisplatin showed that activators of retinoid receptors stimulate nerve growth factor and may improve nerve conduction. Prophylactic dosing with two drugs, acetyl-L-carnitine and olesoxime, known to protect mitochondria, has been shown to significantly reduce the development of pain hypersensitivity to bortezomib in animal models. In another model of oxaliplatin-induced painful neuropathy, improvement in oxidative alterations and pain relief was established with natural antioxidant compounds such as α-tocopherol and silibinin.
The 2011 Cochrane review concluded that the data in human patients are insufficient to conclude that any of the purported chemoprotective agents (acetylcysteine, amifostine, calcium and magnesium, diethyldithiocarbamate, glutathione, Org 2766, oxycarbazepine, or vitamin E) prevent or limit the neurotoxicity of platinum compounds. A randomized phase III clinical trial has recently confirmed that vitamin E did not reduce the incidence of sensory neuropathy. During a validation study of the French FACT/GOG-Ntx questionnaire for assessing CIPN, the study raised the possibility that erythropoietin might play a neuroprotective role when administered with paclitaxel. The successful treatment with vitamin B12 injections in cobalamin deficiency and subacute combined degeneration after nitrous oxide anesthesia is again underscored. Several substances have been studied in the past for treating inflammatory causes of DIPN, and recently melatonin and kinin receptor antagonists have been tested in preclinical models, showing some positive effects.
The outcome of DIPN as a neurological complication associated with immune modulators (TNF[alpha] blockers and alike) has been reported to be favorable in most cases. Although there are no clear-cut recommendations so far on the management of these secondary DIPNs, it is probably advisable to stop the treatment when complications occur, or to treat with steroids or intravenous immunoglobulins.
Treatment
There are no real breakthroughs for the treatment of CIPN. Data from an experimental animal model completed by a randomized controlled trial in patients with nonsmall cell lung cancer treated with cisplatin showed that activators of retinoid receptors stimulate nerve growth factor and may improve nerve conduction. Prophylactic dosing with two drugs, acetyl-L-carnitine and olesoxime, known to protect mitochondria, has been shown to significantly reduce the development of pain hypersensitivity to bortezomib in animal models. In another model of oxaliplatin-induced painful neuropathy, improvement in oxidative alterations and pain relief was established with natural antioxidant compounds such as α-tocopherol and silibinin.
The 2011 Cochrane review concluded that the data in human patients are insufficient to conclude that any of the purported chemoprotective agents (acetylcysteine, amifostine, calcium and magnesium, diethyldithiocarbamate, glutathione, Org 2766, oxycarbazepine, or vitamin E) prevent or limit the neurotoxicity of platinum compounds. A randomized phase III clinical trial has recently confirmed that vitamin E did not reduce the incidence of sensory neuropathy. During a validation study of the French FACT/GOG-Ntx questionnaire for assessing CIPN, the study raised the possibility that erythropoietin might play a neuroprotective role when administered with paclitaxel. The successful treatment with vitamin B12 injections in cobalamin deficiency and subacute combined degeneration after nitrous oxide anesthesia is again underscored. Several substances have been studied in the past for treating inflammatory causes of DIPN, and recently melatonin and kinin receptor antagonists have been tested in preclinical models, showing some positive effects.
The outcome of DIPN as a neurological complication associated with immune modulators (TNF[alpha] blockers and alike) has been reported to be favorable in most cases. Although there are no clear-cut recommendations so far on the management of these secondary DIPNs, it is probably advisable to stop the treatment when complications occur, or to treat with steroids or intravenous immunoglobulins.
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