Evaluating local skin heating as an early detection method for small-fiber neuropathy in women with breast cancer receiving paclitaxel (Taxol®)

Abstract

The purpose of this prospective, observational study was to determine if a technique used to detect early signs of small-fiber neuropathy (local skin heating) could detect signs of small-fiber taxane-induced peripheral neuropathy (TIPN) in breast cancer survivors (BCS) during the first 6 weeks of Taxol®. Aims of the study were to compare the mean size of (1) axon reflexes and (2) axon flares (both markers of small fiber nerve function) in BCS receiving Taxol® to the size of reflexes/flares in healthy female controls (HCs). A third aim was to determine whether the size of axon reflexes/flares correlated with (a) overall TIPN severity and (b) severity of individual signs/symptoms of TIPN during early Taxol®. Data for the study was collected from nine BCS and 20 HCs (N = 29). All BCS had first-time, non-metastatic cancer and received weekly or bi-weekly Taxol®. Data was collected at 3 time-points: Time 1 (day 0, before Taxol®), Time 2 (day 14), and Time 3 (day 42). Axon reflexes and flares were generated using a validated 40-minute skin heating protocol. Axon reflexes were measured using laser Doppler Flowmetry. Axon flares were measured using full-field laser perfusion imaging. TIPN was measured using the 5-item Short Form of the Total Neuropathy Score (Reduced Version). Results identified potential signs of small-fiber TIPN in BCS after 6 weeks of Taxol®. Contrary to expectation, axon reflexes were larger for BCS at Time 3 than HCs, suggesting that Taxol® may be associated with an increase in small-fiber nerve function like that seen in pre-clinical studies. Clinical signs/symptoms of TIPN were not significantly correlated with axon reflexes or axon flares at the same time point. Analyses of axon flare size were confounded by issues with the data. These results add to the growing body of evidence showing that Taxol® affects small-diameter sensory nerves and provides the first evidence in humans that changes in small-fiber nerve function may be detectable after just 6 weeks of Taxol® therapy. Studies in larger samples are needed to validate these findings.