Utidelone-associated chemotherapy-induced peripheral neuropathy: an evidence-stratified narrative review of mechanisms, risk identification, and management strategies.

Utidelone is a genetically engineered epothilone analog and microtubule-stabilizing agent developed in China. It demonstrates antitumor activity in recurrent or metastatic breast cancer after anthracycline and taxane failure. In the pivotal phase III BG01-1323L trial, utidelone plus capecitabine improved progression-free and overall survival versus capecitabine alone; however, peripheral neuropathy occurred in 59% of combination patients, including grade 3 in 22%, versus 8% and less than 1%, respectively, with capecitabine alone. Clinically, neuropathy may impair fine motor function, gait, sleep, and other daily activities, effects not fully captured by toxicity grades alone. Prospective and real-world studies confirm that peripheral neuropathy remains the principal treatment-limiting toxicity of utidelone. Utidelone-specific mechanistic evidence is emerging but remains limited. A 2025 mouse study linked utidelone-induced mechanical and cold allodynia to TRPA1 upregulation and oxidative stress in dorsal root ganglia. Beyond this single preclinical finding, proposed mechanisms--including altered microtubule dynamics, impaired axonal transport, mitochondrial dysfunction, and neuroinflammation--are largely extrapolated from taxane and platinum research. Their relevance to utidelone-induced numbness or persistent deficits in humans remains speculative. Neither ASCO nor ESMO-EONS-EANO recommends routine pharmacologic prophylaxis for chemotherapy-induced peripheral neuropathy (CIPN). Duloxetine has the strongest evidence base for treating established painful CIPN but has not been evaluated specifically for utidelone-associated neuropathy. A small randomized trial found that electroacupuncture produced greater symptomatic improvement than mecobalamin in patients with utidelone-associated neuropathy, although larger confirmatory trials are needed. Evidence supporting monosialotetrahexosylganglioside (GM1), exercise, acupuncture, cryotherapy, compression therapy, or neuromodulation remains preliminary, indirect, or context-dependent. We distinguish utidelone-specific evidence from evidence extrapolated from taxane-, platinum-, and mixed-CIPN populations, because broader CIPN findings are frequently applied to patients receiving utidelone despite uncertain direct applicability. On the basis of available evidence and established CIPN principles, we propose a practical framework integrating pretreatment neurologic and risk assessment, cycle-by-cycle monitoring, symptom-directed supportive care, fall prevention, rehabilitation, and individualized modification of anticancer treatment. Prospective studies are needed to define the onset, cumulative dose-toxicity relationship, persistence, recovery trajectory, and modifiable risk factors of utidelone-associated neuropathy.