Sensory nerve excitability in cancer patients treated with oxaliplatin
Purpose: Nerve dysfunction is a common side effect of oxaliplatin chemotherapy, typically occurring in a dose-dependent manner, so that the higher the dose and the longer exposure time, the more likely neuropathy is to occur. Immediately after administration of oxaliplatin, patients report sensory symptoms, such as paraesthesia in the hands triggered or aggravated by cold exposure.
Methods: To investigate the pathophysiology of oxaliplatin-induced neurotoxicity, nerve excitability studies were undertaken on sensory axons before and after individual paired treatment cycles. Stimulus-responses, strength-duration time constant (SDTC), threshold electrotonus (TE), recovery cycles and current-threshold relations were recorded from a total of 198 cycles of therapy (cycle range: 1-12) in 42 patients.
Results: From the 77 paired cycles, using pre-infusion data from each cycle as the controls, refractoriness decreased significantly by 6.9±2.7% (p<0.01), relative refractory period (RRP) was shortened by 1.13±1.0 ms (p<0.01), superexcitability decreased by 1.4±0.5% (p<0.01) and TE hyperpolarizing (90-100ms) increased by 4.9±2.5% (p<0.05) (mean difference ± SE, paired t-test). Further analysis after categorising 77 paired cycles into early (cycles 1-4) and late (cycles 5-12) groups established that the early cycles of treatment had greater effects on excitability parameters. Later cycles correlated with prolongation in latency (p<0.001), perhaps reflecting the development of neuropathy.
Conclusions: In total, these studies demonstrate that the neurotoxic effects of oxaliplatin may relate to altered axonal Na+ channel function similar to previously documented effects of tetrodotoxin-induced neurotoxicity. The correlation between cycle number and changes in excitability parameters further confirms the cumulative-dose effect of oxaliplatin and suggests a clinical use for nerve excitability testing in predicting neurotoxicity.