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

Vollständiger Abstract

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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.