Effectiveness and safety of traditional Chinese medicine external wash combined with local cooling in preventing UTD1-induced peripheral neuropathy in breast cancer patients: A single-arm, phase II preliminary study.

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Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a prevalent and debilitating toxicity associated with many anticancer agents, frequently leading to dose reduction, treatment delay, or even discontinuation, thereby compromising clinical outcomes. For patients with advanced breast cancer receiving utidelone (UTD1), a next-generation microtubule inhibitor, similar with Ixabepilone, significantly improved the prognosis in advanced breast cancer in BG01-1323L trial. However, the incidence of CIPN reached 85.4%, with 25.1% being grade ≥3 events, underscoring a significant unmet need for effective prevention. Currently, no standardized preventive strategy exists. Traditional Chinese medicine (TCM) external wash with Huangqi Guizhi Wuwu decoction and local cooling have shown potential in preventing CIPN; however, the combined efficacy and safety of these interventions specifically in UTD1-treated patients remain unexplored. Methods: This single-center, single-arm, phase II study enrolled patients with recurrent or metastatic breast cancer who were scheduled to receive UTD1-based chemotherapy (30–40 mg/m² on days 1-3 & 8-9, or days 1-2 & 8-10, every 3 weeks). All patients received the combined intervention, which consisted of local cooling applied via a temperature-controlled device during UTD1 infusion, plus daily external wash with a modified Huangqi Guizhi Wuwu decoction starting from cycle 1 day 1 until completion of chemotherapy (for up to 6 cycles). CIPN was assessed using the NCI-CTC criteria. The primary objective was to evaluate the incidence and severity of CIPN. Results: As of September 2025, 48 patients were evaluable for CIPN analysis. The median age was 56 years (range, 32-74). Over 85% of patients had received ≥3 prior lines of therapy. The overall incidence of CIPN was 62.5% (30/48), with all cases being grade 1-2. Notably, no grade ≥3 CIPN events were observed (0%), compared to 25.1% reported in the historical phase III trial. Compared to the phase III data (N=267, overall CIPN incidence 85.4%), this combined intervention was associated with a statistically significant reduction in overall CIPN incidence (62.5% vs. 85.4%; P<0.001). Conclusions: Preliminary data from this study suggest that the combination of TCM external wash and local cooling significantly reduces the incidence and severity of UTD1-induced CIPN, completely preventing grade ≥3 events. This preventive benefit persisted after UTD1 dose adjustment, no preliminary antitumor efficacy compromise; detailed analyses ongoing. These promising results warrant further RCTs to confirm this modality’s efficacy in UTD1 regimens. Given shared neurotoxicity mechanisms, this non-pharmacological strategy may apply to other regimens with CIPN as a dose-limiting concern.