Paclitaxel Treatment Effects on Neurofilament Light Chain (NF-L), a Possible Biomarker of Chemotherapy-Induced Peripheral Neuropathy (CIPN)

Abstract

Purpose: The purpose of the study was to determine if neurofilament light chain (NF-L), a biomarker of neurologic damage in disease states such as ALS, diabetes, and Parkinson's disease increases with neurotoxic chemotherapy. Methods: Female breast cancer patients (N=21) at two sites (Tucson and Flagstaff. AZ) receiving weekly or biweekly paclitaxel chemotherapy for 3-4 cycles (700-1500mg/m2 total dose) completed blood draws every two weeks. A single molecule array (SiMoA) was used to quantify NF-L levels in serum samples (Quanterix). Patients completed clinical neuropathy grading (CTCAE) and a symptom questionnaire with a neuropathy specific subscale (FACT GOG-Ntx) on day 1 of each paclitaxel cycle and within 30 days of the final treatment to characterize chemotherapy induced peripheral neuropathy (CIPN). The association between cumulative paclitaxel dose and NF-L (log-transformed) or Ntx symptom score (log of score plus one) were tested using linear mixed-effects models, adjusted for site, age, and BMI. The association between cumulative paclitaxel dose and CTCAE neuropathy grade was tested using a multilevel mixed-effects logistic regression model, adjusted for site, age, and BMI. Results: Participants were aged 55.7 ± 11.7 years and with early-stage breast cancer. Serum NF-L increased significantly during taxane chemotherapy: baseline of 38.8 ng/mL; end of study measurement 280.6 ng/mL; p = 0.001. The clinical CTCAE neuropathy grade and self-reported neuropathy symptoms worsened from baseline to end-of-study, with CTCAE of 0.2 ± 0.4 to 1.1 ± 0.6 and Ntx subscale (reversed-scored) of 38.4 ± 6.0 to 30.7 ± 7.6; both p < 0.003. Conclusions: NF-L and CIPN symptoms increased concurrently during taxane treatment. CIPN biomarker qualification is a critical area of survivorship research given the high prevalence of CIPN and the effects of CIPN on pain, quality of life, and dose reductions. Future research with a larger sample, longer follow-up, and objective neuropathic measures may establish whether NF-L can be used to distinguish women who will develop CIPN during taxane treatment versus those who will not.