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

Abstract

Objective Chemotherapy-induced peripheral neuropathy is a prominent side effect of treatment with platinum-based chemotherapies cisplatin and oxaliplatin. Progressive abnormalities in sensory axonal excitability have been linked to neuropathy severity 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/m 2 , 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/m 2 , median 7 months post-completion IQR: 3–30.5). Cisplatin and oxaliplatin-treated patients demonstrated deficits 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 μ V; Ox: 15.7 ± 3.0 μ V; control: 43.9 ± 1.1 μ V, 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 reduction in sensory amplitude. Conclusions Changes in axonal excitability parameters are consistent between platinum-based chemotherapies and linked to neuropathy severity. Significance Platinum analogues demonstrate similar pathophysiological mechanisms of nerve dysfunction. Axonal excitability techniques may provide a marker of axonal dysfunction across different platinum chemotherapies.