Co-occurrence and Metabolic Biomarkers of Sensory and Motor Subtypes of Peripheral Neuropathy from Paclitaxel

Abstract Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) is the major treatment-limiting toxicity of paclitaxel, which predominantly presents as sensory symptoms, with motor symptoms in some patients. Differentiating CIPN into subtypes has been recommended to direct CIPN research. The objective of this study was to investigate whether sensory and motor CIPN are distinct subtypes with different predictive biomarkers in patients with breast cancer receiving paclitaxel.Methods: European Organisation for Research and Treatment of Cancer Quality of Life questionnaire CIPN20 was used to evaluate CIPN. Clusters of the time course of sensory (CIPNS), motor (CIPNM), and the difference between sensory and motor (CIPNS–CIPNM) were identified using k-means clustering on principal component scores. Predictive metabolomic biomarkers of maximum CIPNS and CIPNM were investigated using linear regressions adjusted for baseline CIPN, systemic paclitaxel exposure, and body mass index.Results: More sensory than motor CIPN was found (CIPNS change: mean=10.8, ranged [-3.3, 52.1]; CIPNM change: mean=3.5, range: [-7.5, 35.0]). Three groups were identified with No CIPN, Mixed CIPN, and Sensory-dominant CIPN (maximum CIPNS: mean=12.7 vs. 40.9 vs. 74.3, p<0.001; maximum CIPNM: mean=5.4 vs. 25.5 vs. 36.1, p<0.001; average CIPNS–CIPNM: mean=2.8 vs. 5.8 vs. 24.9, p<0.001). Biomarkers of motor CIPN were similar to previously identified biomarkers of sensory CIPN, including lower serum histidine (p=0.029).Conclusion: Our findings suggest that sensory and motor CIPN co-occur and may not have differentiating metabolic biomarkers. These findings need to be validated in larger cohorts of patients treated with paclitaxel and other neurotoxic agents to determine the optimal approach to predict, prevent, and treat CIPN and improve patients’ outcomes.