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Platinum-Induced Neurotoxicity and Preventive Strategies: Past, Present, and Future
- Source :
- Avan, A, Postma, T J, Ceresa, C, Avan, A, Cavaletti, G, Giovannetti, E & Peters, G J 2015, ' Platinum-Induced Neurotoxicity and Preventive Strategies: Past, Present, and Future ', The Oncologist, vol. 20, no. 4, pp. 411-432 . https://doi.org/10.1634/theoncologist.2014-0044, The Oncologist, 20(4), 411-432. AlphaMed Press
- Publication Year :
- 2015
- Publisher :
- Oxford University Press (OUP), 2015.
-
Abstract
- Neurotoxicity is a burdensome side effect of platinum-based chemotherapy that prevents administration of the full efficacious dosage and often leads to treatment withdrawal. Peripheral sensory neurotoxicity varies from paresthesia in fingers to ataxic gait, which might be transient or irreversible. Because the number of patients being treated with these neurotoxic agents is still increasing, the need for understanding the pathogenesis of this dramatic side effect is critical. Platinum derivatives, such as cisplatin and carboplatin, harm mainly peripheral nerves and dorsal root ganglia neurons, possibly because of progressive DNA-adduct accumulation and inhibition of DNA repair pathways (e.g., extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase/stress-activated protein kinase, and p38 mitogen-activated protein kinass), which finally mediate apoptosis. Oxaliplatin, with a completely different pharmacokinetic profile, may also alter calcium-sensitive voltage-gated sodium channel kinetics through a calcium ion immobilization by oxalate residue as a calcium chelator and cause acute neurotoxicity. Polymorphisms in several genes, such as voltage-gated sodium channel genes or genes affecting the activity of pivotal metal transporters (e.g., organic cation transporters, organic cation/carnitine transporters, and some metal transporters, such as the copper transporters, and multidrug resistance-associated proteins), can also influence drug neurotoxicity and treatment response. However, most pharmacogenetics studies need to be elucidated by robust evidence. There are supportive reports about the effectiveness of several neuroprotective agents (e.g., vitamin E, glutathione, amifostine, xaliproden, and venlafaxine), but dose adjustment and/or drug withdrawal seem to be the most frequently used methods in the management of platinum-induced peripheral neurotoxicity. To develop alternative options in the treatment of platinum-induced neuropathy, studies on in vitro models and appropriate trials planning should be integrated into the future design of neuroprotective strategies to find the best patient-oriented solution.
- Subjects :
- Cancer Research
Neurotoxicity Syndrome
Antineoplastic Agents
Platinum Compounds
Pharmacology
Neuroprotection
chemistry.chemical_compound
Pathogenesi
Neurotoxicity
medicine
Humans
Polymorphism
Neuro-Oncology
Protein kinase A
Xaliproden
Platinum
Cisplatin
Polymorphism, Genetic
Organic cation transport proteins
biology
business.industry
Prevention
medicine.disease
Carboplatin
Neuroprotective Agents
Oncology
chemistry
Pharmacogenetics
biology.protein
Neurotoxicity Syndromes
business
Model
medicine.drug
Subjects
Details
- ISSN :
- 1549490X and 10837159
- Volume :
- 20
- Database :
- OpenAIRE
- Journal :
- The Oncologist
- Accession number :
- edsair.doi.dedup.....1f2ce7e2a936ab4c34d44e1ba3e4e36e