Değerli Ezgi
Bakırköy Dr. Sadi Konuk Research and training Hospital, Department of Medical Oncology, Istanbul, Turkey.
J Oncol Pharm Pract. 2025 Mar;31(2):325-328. doi: 10.1177/10781552241279831. Epub 2024 Aug 28.
IntroductionBreast cancer, the most prevalent cancer among women, often requires chemotherapy with docetaxel being a key agent. However, docetaxel-inducted peripheral neuropathy (DIPN) can adversely impact patients' quality of life. This case discusses an unusual instance of severe DIPN leading to wheelchair dependence in a 35-years old woman undergoing neoadjuvant treatment for locally advanced breast cancer.CaseFollowing anthracycline and cyclophosphamide cycles without neurological symptoms, docetaxel administration resulted in progressive neuropathy. Despite dose reduction, the patient developed severe paraesthesias, foot weakness, and eventually wheelchair dependence.Management and outcomeDocetaxel's microtubule-stabilizing mechanism, vital for cell division, may disrupt axonal structures, causing sensory and motor neuropathy. While rare, severe motor neuropathy, leading to wheelchair dependence, poses a significant challenge. The frequency of DIPN varies, with docetaxel exhibiting lower neuropathy rates than other taxanes. Risk factors include age, diabetes mellitus, cumulative dose, and genetic polymorphisms in GSTP1 and ABCB1. In our case, despite the patient being young, fit and without diabetes, severe DIPN occured, suggesting a potential genetic predisposition. Genetic variations, such as GSTP1 polymorphisms have been associated with DIPN. Our patient carried GSTP1 (I1e105Val) mutations, emphasizing the need for further research to establish their role as risk factors.DiscussionThis case underscores the importance of recognizing severe DIPN, even in atypical patient profiles. Genetic factors, like GSTP1 polymorphisms, may contribute to DIPN risk. Large-scale studies are crucial to establishing the significance of these genetic variations in DIPN susceptibility.
引言
乳腺癌是女性中最常见的癌症,通常需要使用多西他赛进行化疗,多西他赛是关键药物。然而,多西他赛诱导的周围神经病变(DIPN)会对患者的生活质量产生不利影响。本病例讨论了一名35岁接受局部晚期乳腺癌新辅助治疗的女性发生严重DIPN并导致依赖轮椅的罕见情况。
病例
在接受蒽环类药物和环磷酰胺治疗且无神经症状后,使用多西他赛导致进行性神经病变。尽管减少了剂量,患者仍出现严重的感觉异常、足部无力,最终依赖轮椅。
管理与结果
多西他赛的微管稳定机制对细胞分裂至关重要,但可能会破坏轴突结构,导致感觉和运动神经病变。虽然严重的运动神经病变导致依赖轮椅的情况罕见,但却是一个重大挑战。DIPN的发生率各不相同,多西他赛的神经病变发生率低于其他紫杉烷类药物。风险因素包括年龄、糖尿病、累积剂量以及GSTP1和ABCB1的基因多态性。在我们的病例中,尽管患者年轻、健康且无糖尿病,但仍发生了严重的DIPN,提示可能存在潜在的遗传易感性。诸如GSTP1多态性等基因变异与DIPN有关。我们的患者携带GSTP1(I1e105Val)突变,强调需要进一步研究以确定其作为风险因素的作用。
讨论
本病例强调了认识到严重DIPN的重要性,即使在非典型患者中也是如此。像GSTP1多态性这样的遗传因素可能会增加DIPN的风险。大规模研究对于确定这些基因变异在DIPN易感性中的重要性至关重要。