Nguyen-Hoang Nam, Nazzal Maisa, Schneider Bryan P, Trivedi Meghna S, Hertz Daniel L
Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI 48109, USA.
Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN 46202, USA.
Crit Rev Oncol Hematol. 2025 Jul;211:104739. doi: 10.1016/j.critrevonc.2025.104739. Epub 2025 Apr 22.
Taxanes are first-line chemotherapy for several solid tumors, but their use is often limited by taxane-induced peripheral neuropathy (TIPN), which can cause acute symptoms in up to 70 % of patients and severely deteriorate long-term quality of life. Recent evidence from large prospective observational studies confirms a dramatic racial disparity, with Black/African-ancestry patients facing roughly two times greater risk of TIPN compared to White patients. Understanding the root causes of this disparity is a critical first step toward eliminating inequities in cancer treatment side effects, aligning with a major goal of the U.S. National Cancer Institute's National Cancer Plan. This review examines clinical and genetic factors contributing to racial differences in TIPN, focusing on those that have been associated with TIPN risk and are more prevalent within Black/African-ancestry individuals. Pre-existing neuropathy, vitamin D insufficiency, metabolic risk factors (obesity/diabetes), systemic taxane exposure, and genetic variants are discussed as potential contributors to this racial disparity. The review concludes by describing additional research that is needed to determine which of these factors are responsible for this disparity and what types of translational clinical studies could be conducted to target these mechanisms and reduce inequity. These findings could inform clinical strategies that improve long-term quality of life and promote health equity in taxane-treated cancer patients in the U.S. and globally.
紫杉烷类药物是多种实体瘤的一线化疗药物，但其应用常受紫杉烷类药物引起的周围神经病变（TIPN）限制，高达70%的患者会出现急性症状，严重影响长期生活质量。大型前瞻性观察研究的最新证据证实了显著的种族差异，与白人患者相比，黑人/非裔患者发生TIPN的风险大约高出两倍。了解这种差异的根本原因是消除癌症治疗副作用方面不平等现象的关键第一步，这与美国国立癌症研究所《国家癌症计划》的一个主要目标相一致。本综述探讨了导致TIPN种族差异的临床和遗传因素，重点关注那些与TIPN风险相关且在黑人/非裔个体中更为普遍的因素。既往存在的神经病变、维生素D缺乏、代谢风险因素（肥胖/糖尿病）、全身紫杉烷暴露和基因变异被讨论为这种种族差异的潜在促成因素。综述最后描述了确定这些因素中哪些是造成这种差异的原因以及可以开展哪些类型的转化临床研究来针对这些机制并减少不平等现象所需的其他研究。这些发现可为改善美国及全球接受紫杉烷治疗的癌症患者长期生活质量和促进健康公平的临床策略提供参考。
