Bakry Hala M, Mansour Noha O, ElKhodary Tawfik R, Soliman Moetaza M
Clinical Pharmacy and Pharmacy Practice Department, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
Oncology Center, Medical Oncology Unit, Mansoura University, Mansoura, Egypt.
Front Pharmacol. 2023 Jul 31;14:1181312. doi: 10.3389/fphar.2023.1181312. eCollection 2023.
Paclitaxel-induced peripheral neuropathy (PN) is a serious clinical problem with no approved drug for prevention. This study aimed to examine the neuroprotective effect of metformin against paclitaxel-induced PN in breast cancer patients. Patients with confirmed breast cancer diagnosis who were planned to receive paclitaxel were randomized to receive either metformin or placebo. Both groups received the standard chemotherapy protocol for breast cancer. Patients started metformin/placebo 1 week before paclitaxel initiation and continued study interventions thereafter for nine consecutive weeks. The primary outcome was the incidence of development of grade two or more paclitaxel-induced sensory PN. The PN was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). Patients' quality of life (QoL) was assessed by the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACTGOG-Ntx) subscale. Pain severity was measured by the Brief Pain Inventory Short Form (BPI-SF). Serum levels of nerve growth factor (NGF) and neurotensin (NT) were measured at baseline and at the end paclitaxel treatment. A total of 73 patients (36 in the metformin arm and 37 in the control arm) were evaluated. The cumulative incidence of development of grade two or more PN was significantly lower in the metformin arm (14 (38.9%) than the control arm (28 (75.7%); = 0.001). At the end of paclitaxel treatment, patients' QoL was significantly better in the metformin arm [median (IQR) FACTGOG-Ntx subscale of (24.0 (20.5-26.5)] compared to the control arm (21.0 (18.0-24.0); = 0.003). The metformin arm showed lower "average" and "worst" pain scores than those detected in the control arm. At the end of the paclitaxel treatment, there was a significant difference in the median serum NGF levels between the two arms, favoring metformin ( < 0.05), while NT serum levels were deemed comparable between the two study arms ( = 0.09). The use of metformin in breast cancer patients offered a marked protection against paclitaxel-induced PN, which translated to better patient QoL. : https://classic.clinicaltrials.gov/ct2/show/NCT05351021, identifier NCT05351021.
紫杉醇引起的周围神经病变（PN）是一个严重的临床问题，目前尚无获批用于预防的药物。本研究旨在探讨二甲双胍对乳腺癌患者紫杉醇诱导的PN的神经保护作用。确诊为乳腺癌且计划接受紫杉醇治疗的患者被随机分为接受二甲双胍或安慰剂组。两组均接受乳腺癌标准化疗方案。患者在开始使用紫杉醇前1周开始服用二甲双胍/安慰剂，并在之后连续9周继续进行研究干预。主要结局是二级或更高级别的紫杉醇诱导的感觉性PN的发生频率。PN根据美国国立癌症研究所不良事件通用术语标准（NCI-CTCAE）进行分级。通过癌症治疗功能评估/妇科肿瘤学组神经毒性（FACTGOG-Ntx）子量表评估患者的生活质量（QoL）。疼痛严重程度通过简明疼痛量表简表（BPI-SF）进行测量。在基线和紫杉醇治疗结束时测量血清神经生长因子（NGF）和神经降压素（NT）水平。总共评估了73例患者（二甲双胍组36例，对照组37例）。二甲双胍组二级或更高级别PN的累积发生率显著低于对照组（14例（38.9%）比28例（75.7%）；P = 0.001）。在紫杉醇治疗结束时，二甲双胍组患者的QoL明显优于对照组[FACTGOG-Ntx子量表的中位数（IQR）为24.0（20.5 - 26.5）]，而对照组为21.0（18.0 - 24.0）；P = 0.003）。二甲双胍组的“平均”和“最严重”疼痛评分低于对照组。在紫杉醇治疗结束时，两组之间的血清NGF中位数水平存在显著差异，二甲双胍组更具优势（P < 0.05），而两组之间的血清NT水平被认为相当（P = 0.09）。在乳腺癌患者中使用二甲双胍对紫杉醇诱导的PN具有显著的保护作用，这转化为更好的患者QoL。：https://classic.clinicaltrials.gov/ct2/show/NCT05351021，标识符NCT05351021
