A review on oxaliplatin-induced peripheral nerve damage.
Platinum compounds are a class of chemotherapy agents that posses a broad spectrum of activity against several solid malignancies. Oxaliplatin (OXL) is a third-generation organoplatinum compound with significant activity mainly against colorectal cancer (CRC). Peripheral neuropathy is a well recognized toxicity of OXL, usually resulting in dose modification. OXL induces two types of peripheral neuropathy; acute and chronic. The acute oxaliplatin-induced peripheral neuropathy (OXLIPN) may be linked to the rapid chelation of calcium by OXL-induced oxalate and OXL is capable of altering the voltage-gated sodium channels through a pathway involving calcium ions. On the other hand, decreased cellular metabolism and axoplasmatic transport resulting from the accumulation of OXL in the dorsal root ganglia cells is the most widely accepted mechanism of chronic oxaliplatin-induced peripheral neuropathy (OXLIPN). As a result, OXL produces a symmetric, axonal, sensory distal primary neuronopathy without motor involvement. The incidence of OXLIPN is usually related to various risk factors, including treatment schedule, dosage, cumulative dose and time of infusion. The assessment of OXLIPN is primarily based on neurologic clinical examination and quantitative methods, such as nerve conduction study. To date, several neuroprotective agents including thiols, neurotrophic factors, anticonvulsants and antioxidants have been tested for their ability to prevent OXLIPN. However, the clinical data are still controversial. We herein review and discuss the pathogenesis, incidence, risk factors, diagnosis, characteristics and management of OXLIPN. We also highlight areas of future research.
Argyriou
Andreas A
AA
Department of Neurology, EMG Laboratory, University of Patras Medical School, Rion-Patras, Greece.
Polychronopoulos
Panagiotis
P
Iconomou
Gregoris
G
Chroni
Elisabeth
E
Kalofonos
Haralabos P
HP
D005727:Ganglia, Spinal / Q000378:metabolism; D006801:Humans; D015994:Incidence; D018696:Neuroprotective Agents / Q000627:therapeutic use; D009944:Organoplatinum Compounds / Q000009:adverse effects*; D000077150:Oxaliplatin; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000517:prevention & control / Q000628:therapy; D012307:Risk Factors; D028761:Withholding Treatment
D018696:Neuroprotective Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin