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Peripheral Nervous System

 

Cisplatinum Related Neuropathy

 

Cisplatinum

• Predominantly causes a sensory peripheral neuropathy affecting large nerve fibres³
• The dorsal root ganglion is the primary target⁸
• The dose-limiting neurotoxicity occurs at dosages above 200 mg/m2⁵
• 57-92% of patients treated with cisplatin develop peripheral neuropathy³

 

Carboplatinum

• Much less likely to cause peripheral neuropathy than cisplatinum, unless doses are exceedingly high
• Due to its stable cyclobutane leaving group and efficient excretion in urine¹

 

Oxaliplatin

• Newer platinum analog that causes cisplatin-like peripheral neuropathy in 80% of patients
• Also precipitates acute neuropathy (cold-induced dysthesias in hands/feet, jaw tightness, pharyngo-laryngo-dysesthesia) 30-60 min after administration if doses exceed 540 mg/m².
• This is thought to be due to the ability of oxaliplatin to alter axonal ion conductance and excitability³.

 

Mechanism:

• The mechanism of cisplatin-induced neuropathy is unknown, but may involve the binding of DNA in the dorsal root ganglion which triggers apoptosis and premature neuronal cell death⁵

 

Symptoms:

The time course of cisplatin-induced symptoms is unusual compared to the peripheral neuropathy caused by other chemotherapeutic agents in that it occurs very late or after treatment has been completed³.

• Paresthesias and dysesthesias in hands and feet
• Position and vibration sense disturbed (large fibres affected)
• Autonomic dysfunction is rare, but may involve orthostatic hypotension
• Motor dysfunction may occur after substantial sensory loss

 

Investigation:

• Sensory nerve conduction studies show:
  • Decrease or absence of sensory nerve action potentials
  • Delayed sensory nerve conduction velocities
• Motor nerve conduction and EMG are normal

 

Risk factors:

• Cumulative dose
  • Peripheral neuropathy occurs when the cumulative dose becomes greater than 300 mg/m²
  • Severe symptoms arise when greater than 500 mg/m2³ 
• Type of platinum compound and daily dose³
• Amofostine has a protective effect on subclinical neurotoxicity when given with cisplatinum.

 

Prognosis:

• Severe acute neurotoxicity usually resolves – two thirds of patients will have complete recovery³
• 20-60% of patients may be left with persistent paresthesias following therapy

 

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