Early changes in tests of peripheral nerve function during oxaliplatin treatment and their correlation with chemotherapy‐induced polyneuropathy symptoms and signs

Abstract

Background and purpose Assessment of the severity of chronic peripheral neuropathy during oxaliplatin treatment is based on symptoms. Efforts to adjust the total dose of oxaliplatin to prevent severe neuropathy can be complicated by the worsening of neuropathy symptoms following treatment. Objective measures of the structure and function of peripheral nerves during early phases of treatment may aid in determining the optimal oxaliplatin dose in individual patients. Intraepidermal nerve fibre density (IENFD) has been suggested as an early marker of peripheral neuropathy. Methods Sixty patients were examined before treatment and following 25% and 50% of the total planned oxaliplatin dose. Fifty‐five of them were also examined at completion of chemotherapy and 6 months later. IENFD in skin biopsies from the distal leg, nerve conduction studies and quantitative sensory testing at the dorsum of the foot were performed. Forty‐six healthy subjects were examined at baseline and after 6 and 52 weeks for comparison. Results Intraepidermal nerve fibre density was not reduced during treatment. Sural nerve amplitude and conduction velocity, vibration detection thresholds, mechanical detection threshold and cold detection threshold were significantly reduced during treatment. Compared to reference values and spontaneous changes in healthy subjects, the largest proportions of patients with deterioration were found for vibration detection thresholds followed by nerve conduction studies, mechanical detection threshold, cold detection threshold and IENFD. Conclusions Significant changes were most pronounced for measures of large nerve fibre function, especially vibration sensation. Skin biopsies do not seem to provide a clinically relevant objective measure of peripheral nerve deterioration during oxaliplatin treatment.

Impact of Chemotherapy-Induced Peripheral Neuropathy on Quality of Life in Patients with Advanced Lung Cancer Receiving Platinum-Based Chemotherapy

“…Finally, patients’ initial (pre-treatment) peripheral neurological function and lifestyle, variables not studied here, may have affected the evaluation of CIPN. Further studies are needed to determine the correlation between initial peripheral neurological function, lifestyle, and CIPN [ 48 ].…”

Predictive Biomarkers of Oxaliplatin-Induced Peripheral Neurotoxicity

“…Several longitudinal studies, including NCS during OXA therapy, have showed a significant progressive decrease in sensory nerve action potentials (SNAPs) and preservation of motor action compound (CMAPs), in keeping with the presence of an axonal sensory neuropathy, and consistent with the clinical symptoms and signs worsening during the treatment [ 17 , 41 , 58 , 59 , 60 , 61 , 62 , 63 , 64 ]. NCS are capable of objectively assessing the extent of peripheral nerve damage and may also facilitate the identification of patients that manifest subclinical peripheral neuropathy prior to the onset of clinically significant neurotoxicity.…”

“…After sensory examination, reductions in upper and lower limb SNAPs of patients were the most sensitive early markers of neuropathy observed in 40% [ 69 ]. In this line, in one prospective study including 60 gastrointestinal cancer patients, sural nerve velocity and SNAP revealed a significant decrease after 50% and 100% of the planned dose, respectively [ 60 ].…”

“…However, conflicting results regarding the predictive role of early changes in VDT are seen in the literature. Whereas VDT in 30 patients with gastrointestinal malignancies receiving OXA evaluated at baseline and during infusion cycles 1, 2, 4, and 6, showed no clear relationship with OXAIPN development [ 80 ], two studies including 17 [ 69 ] and 60 patients [ 60 ] showed being the earliest marker of neuropathy, present at low cumulative doses of OXA. Significant change in VDT were present after the 25% of the planed dose, being the earliest among other measures [ 60 ].…”

“…Whereas VDT in 30 patients with gastrointestinal malignancies receiving OXA evaluated at baseline and during infusion cycles 1, 2, 4, and 6, showed no clear relationship with OXAIPN development [ 80 ], two studies including 17 [ 69 ] and 60 patients [ 60 ] showed being the earliest marker of neuropathy, present at low cumulative doses of OXA. Significant change in VDT were present after the 25% of the planed dose, being the earliest among other measures [ 60 ]. Very recently, Kroigard et al identified VDT measure obtained before treatment correlated as a predictor of clinically significant OXAIPN six months post-treatment.…”