Peripheral Nervous System
Cisplatinum Related Neuropathy
- 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
- 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
- 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.
- 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
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
- 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
- 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.
- 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