Oncology Clinical Pharmacy Department, Nasser Institute for Research and Treatment, Cairo, Egypt.
Clinical Pharmacy Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
Breast Cancer Res Treat. 2020 Aug;183(1):117-125. doi: 10.1007/s10549-020-05762-8. Epub 2020 Jun 29.
The aim of the current study was to evaluate the effect of N-acetylcysteine (NAC) on the incidence and severity of paclitaxel-induced peripheral neuropathy (PIPN) in breast cancer patients.
A prospective randomized controlled open label study was conducted on 75 breast cancer patients receiving adjuvant paclitaxel 80 mg/m weekly for 12 weeks. Eligible patients were randomized to either the low dose group; 1200 mg daily NAC, the high dose group; 1200 mg NAC twice daily or the control group; received paclitaxel only. The primary endpoint was the incidence of different grades of PIPN using National Cancer Institute's common toxicity criteria for adverse event (NCI-CTCAE) while secondary endpoints were the severity of PIPN using modified total neuropathy score (mTNS), quality of life (QOL) using Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT-GOG-NTX) subscale, serum nerve growth factor (NGF), and serum malondialdehyde (MDA).
At the end of the 12-week period, the incidence of grade (2, 3) peripheral neuropathy was significantly lower in the high dose group (28.6%) compared to the low dose group (61.9%) and the control group (100%), p value < 0.001. A significant improvement in the mTNS and QOL scores was observed after 6 and 12 weeks in the high dose group and the low dose group compared to the control, p value < 0.001. Significantly higher levels of serum NGF in the high dose group and lower level of serum MDA in the high dose and the low dose group were observed.
Oral NAC (1200 mg once and twice daily) might reduce the incidence and severity of PIPN and improve the patients' QOL.
Clinical Trial.gov registration number: NCT03492047.
本研究旨在评估 N-乙酰半胱氨酸（NAC）对乳腺癌患者紫杉醇诱导的周围神经病变（PIPN）发生率和严重程度的影响。
对 75 例接受每周 80mg/m2 紫杉醇辅助治疗 12 周的乳腺癌患者进行了一项前瞻性随机对照开放标签研究。符合条件的患者被随机分为低剂量组（每天 1200mg NAC）、高剂量组（每天两次 1200mg NAC）或对照组（仅接受紫杉醇治疗）。主要终点为使用国立癌症研究所不良事件通用毒性标准（NCI-CTCAE）评估不同分级 PIPN 的发生率，次要终点为使用改良总神经病变评分（mTNS）评估 PIPN 的严重程度、使用癌症治疗功能评估/妇科肿瘤学组神经毒性（FACT-GOG-NTX）量表评估生活质量（QOL）、血清神经生长因子（NGF）和血清丙二醛（MDA）。
在 12 周结束时，高剂量组（28.6%）的（2、3 级）周围神经病变发生率明显低于低剂量组（61.9%）和对照组（100%），p 值<0.001。与对照组相比，高剂量组和低剂量组在第 6 和 12 周时 mTNS 和 QOL 评分均显著改善，p 值<0.001。高剂量组血清 NGF 水平显著升高，高剂量和低剂量组血清 MDA 水平显著降低。
口服 NAC（每天 1200mg 一次和两次）可能降低 PIPN 的发生率和严重程度，并改善患者的 QOL。
ClinicalTrials.gov 注册号：NCT03492047。
