(T1130-10-66) Factors Affecting Peripheral Neuropathy Induced by Nab-paclitaxel in Patients with Pancreatic Cancer

Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the major toxicities that limit the use of taxane compounds for the treatment of cancer patients. Imperative is to identify the associated risk factors of CIPN, given the absence of effective prevention of CIPN. The assessment of the identifiable risk factors in the treatment of patients with pancreatic cancer with nab-paclitaxel (nab-P) appears to assist in averting the occurrence or progression of CIPN, thereby preserving the patient’s quality of life. The objective of this study was to evaluate the association of CIPN with demographic, clinical and pharmacokinetic factors in pancreatic cancer patients using patient-reported outcome measure and minimally invasive volumetric absorptive microsampling (VAMS) method.

Methods: Recruited in this study were newly diagnosed patients with pancreatic cancer who are to undergo chemotherapy treatment with nab-P/gemcitabine. The demographic and clinical data of the study participants were collected from the electronic medical record of the participating hospital. Most study participants received the dose of nab-P 125 mg/m² body surface area via intermittent intravenous infusion each cycle of chemotherapy that consisted of three weeks of drug administration and one week break. Blood samples were collected using 20-μL tips of VAMS from the patient’s finger immediately before the end of nab-P infusion to obtain the maximum concentration of paclitaxel (C_max) on the first day of each cycle and stored at -70°C. The concentrations of paclitaxel in VAMS samples were measured using a high-performance liquid chromatographic method with tandem mass spectrometric detection. CIPN was assessed using the eight sensory questionnaires of the European Organization of Research and Treatment of Cancer - Quality of Life Questionnaire - CIPN (EORTC-QLQ CIPN8) before the infusion of nab-P on the first day of each cycle. The assessed CIPN8 scores ranging from eight to thirty-two were linearly converted into a 0-100 scale. In addition, the severity of CIPN was expressed using the converted CIPN8 score changed from the baseline. Univariate and multivariate Spearman rank correlation analyses were performed to evaluate the factors associated with the severity of CIPN. Multiple linear regression was performed to evaluate the association between C_max and the number of treatment cycles (Cycle), and the severity of CIPN.

Results: The clinical and nab-P concentration data obtained from a total of 34 patients were included in the analyses. The data consist of 52 VAMS samples, 77 clinical lab test values and 85 CIPN8 scores. The mean ± standard deviation (SD) values (range) of the dose, infusion time and C_max of nab-P were 115.5 ± 13.0 (61.7 – 130) mg/m², 24.1 ± 4.2 (11 – 36) min and 5.51 ± 3.11 (0.15 – 14.64) μg/mL, respectively. The mean ± SD value (range) of the baseline CIPN8 score was 0 ± 0 (0 – 0). In univariate Spearman rank correlation analysis, the converted CIPN8 score was significantly correlated with an increase in cumulative dose (D_cum, ρ = 0.587, p < 0.0001; 95% confidence interval [95% CI], 0.422 – 0.714), Cycle (ρ = 0.581, p < 0.0001; 95% CI, 0.414 – 0.710), C_max (ρ = 0.300, p = 0.031; 95% CI, 0.021 – 0.535) and hematocrit (Hct, ρ = 0.247, p = 0.030; 95% CI, 0.018 – 0.452). In a multivariate Spearman rank correlation analysis, the converted CIPN8 score was significantly correlated with Cycle and C_max (ρ = 0.430, p = 0.001; ρ = 0.300, p = 0.031, respectively), meaning that Cycle and C_max need to be considered simultaneously in evaluating the severity of CIPN. Similarly, based on a multiple linear regression analysis, the severity of CIPN was predictable from Cycle and C_max.

Conclusion: The severity of CIPN is significantly related to the number of treatment cycles and the C_max of nab-P. The higher the cycle and/or C_max of nab-P, the more severely do the patients experience peripheral neuropathy associated with nab-P administration. The correlation between the C_max and the severity of CIPN indicates the use of minimally invasive VAMS is feasible as an alternative to venous blood sampling for predicting the severity.

Acknowledgements: This study was approved by the Institutional Review Board (IRB) of Seoul National University Hospital (IRB number: H-2103-093-1205). This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2021R1F1A104996113). This work was also supported by Research Institute of Pharmaceutical Sciences and the four phase of the Brain Korea 21 Program in 2023.