Baseline Peripheral Neuropathy Predicts Clinically Significant Neuropathy During Paclitaxel Treatment Following Oxaliplatin-based Chemotherapy

Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting toxicity that adversely affects quality of life and treatment continuity of patients with malignancy. Although cumulative oxaliplatin exposure is a recognized risk factor for neurotoxicity, it remains unclear whether cumulative exposure or baseline neurological status better predicts clinically significant CIPN during subsequent paclitaxel treatment. This study aimed to identify predictors of clinically significant CIPN during paclitaxel therapy, focusing on the relative predictive value of cumulative oxaliplatin exposure and baseline CIPN.

We retrospectively reviewed 76 patients with advanced gastric cancer who received paclitaxel-based second-line therapy after oxaliplatin-containing first-line chemotherapy. The primary endpoint was time to development of grade ≥2 CIPN, and the secondary endpoint was CIPN worsening. Cox proportional hazards and multivariable logistic regression analyses were performed to identify factors associated with CIPN progression.

Grade ≥2 CIPN developed in 34 patients (44.7%). Baseline CIPN (grade 1 vs. 0) independently predicted subsequent grade ≥2 CIPN (hazard ratio=4.23, 95% confidence interval=1.67-10.72; p=0.002; odds ratio=5.00, 95% confidence interval=1.58-15.80; p=0.006). In contrast, cumulative oxaliplatin dose was not associated with grade ≥2 CIPN or CIPN worsening. Kaplan-Meier analysis also showed no association between cumulative oxaliplatin dose and time to CIPN worsening, whereas higher serum albumin levels tended to be associated with a lower risk of CIPN progression.

Baseline CIPN was a stronger predictor of clinically significant neuropathy during paclitaxel treatment than prior cumulative oxaliplatin exposure. Routine assessment of baseline neurological status before paclitaxel initiation may help identify patients at high risk for clinically significant CIPN and support individualized treatment and monitoring strategies.