Neurophysiological dysfunction in chemotherapy-treated 206 patients: Comparison of different platinum analogues

Objective: Chemotherapy-induced peripheral neuropathy is a 218 prominent side effect of treatment with platinum-based chemotherapies cisplatin and oxaliplatin. Progressive abnormalities in sensory axonal excitability have been linked to neuropathy sever- ity in oxaliplatin-treated patients, but not examined in cisplatin- treated patients. Methods: Sensory axonal excitability studies were undertaken in median nerve. Neuropathy was assessed via total neuropathy score reduced (TNSr). Results: Clinical severity of neuropathy was greater (TNSr: 6.9 ± 1.2) in oxaliplatin-treated patients (N = 16, Age: 57.1 ± 3 years, cumulative dose: 801 ± 63.5 mg/m2, median 6 months post- completion IQR: 4-12.5) than in cisplatin-treated patients (TNSr: 3.2 ± 0.6, p < :01, N = 17, Age: 48.5 ± 4.3 years, cumulative dose: 316.5 ± 19.3 mg/m2, median 7 months post-completion IQR: 3- 30.5). Cisplatin and oxaliplatin-treated patients demonstrated defi- cits in sensory nerve function compared to controls, with increased threshold change in excitability (TEh90-100 ms Cis: -128.7 ± 4.7%; Ox: -140.9 ± 5.9%; control: -116.6 ± 3.1%, p < :01) and reduced median sensory amplitudes (Cis: 24.4 ± 3.0 μV; Ox: 15.7 ± 3.0 μV; control: 43.9 ± 1.1 μV, p < :01) with greater abnormalities in oxaliplatin-treated patients (p < :01). TEh90-100 ms was correlated to median amplitude (r = .418, p < :05), with patients demonstrating greater excitability abnormalities also demonstrating greater reduc- tion in sensory amplitude. Conclusions: Changes in axonal excitability parameters are consis- tent between platinum-based chemotherapies and linked to neu- ropathy severity. Significance: Platinum analogues demonstrate similar pathophysi- ological mechanisms of nerve dysfunction. Axonal excitability tech- niques may provide a marker of axonal dysfunction across different platinum chemotherapies.