Weekly Paclitaxel-Induced Neurotoxicity in Breast Cancer: Outcomes and Dose Response.

Abstract

Paclitaxel treatment produces significant peripheral neuropathy, but the time course of neuropathy development and outcomes are unclear. Dose reduction is the only strategy to prevent neurotoxicity, however, the impact of dose-reduction on neuropathy outcomes remains unknown. This study aimed to prospectively evaluated neuropathy development from weekly paclitaxel treatment and evaluate the impact of dose-reduction on post-treatment neuropathy outcomes. Breast cancer patients receiving paclitaxel (80mg/m2 ) weekly for 12-weeks were prospectively assessed using patient reported (Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity; FACTGOG-Ntx), clinical (Total Neuropathy Score clinical version; TNSc) and neurophysiological measures up to 12-months post completion. The impact of dose-reduction on post-treatment (3.6 ± 0.1 months) clinical and patient reported outcomes was evaluated in 105 weekly paclitaxel-treated patients. Significant neuropathy was present by 6-weeks across patient-reported, clinical, and objective neurophysiological assessments, increasing in prevalence and severity over the treatment course. Limited recovery occurred, with significant neuropathy being maintained up to 12 months (p < .05). Patients who received dose reduction had worse patient reported (FACT-GOG-Ntx: 40.2 ± .1.4) and clinical neuropathy outcomes (TNSc: 4.3 ± 0.4) compared to those who received the full dose (FACT-GOG-Ntx: 45.9 ± 0.9; TNSc: 3.3 ± 0.3, p < .05). Patients who ceased treatment early demonstrated the worse deficits (TNSc: 5.0 ± 0.6; FACT-GOG-Ntx: 37.3 ± 2.7) compared to those who received the complete dose (TNSc: 3.5 ± 0.3; FACT-GOG-Ntx: 45.3 ± 0.9, p < .05). Weekly paclitaxel produces symptomatic and objective neuropathy early in the treatment course which can persist. Dose reduction does not necessarily lead to more favorable neuropathy outcomes, with individual risk factors likely important in addition to cumulative dose. Weekly paclitaxel schedules are extensively used in breast cancer. Patients may develop symptomatic and objective neuropathy early in the treatment course, with these individuals requiring closer monitoring. Furthermore, neuropathy is a long-term sequela that may impact quality of life and require appropriate supportive services. Results suggest that dose reduction does not necessarily lead to better neuropathy outcomes. Understanding schedule-specific toxicity and risk factors for neuropathy will be critical to determining individualized treatment strategies and improving quality of life in breast cancer survivors.