Clinical Pharmacy and Pharmacy Practice Department, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
Medical Oncology Unit, Oncology Center, Mansoura University, Mansoura, Egypt.
Pharmacotherapy. 2023 Sep;43(9):872-882. doi: 10.1002/phar.2830. Epub 2023 Jun 12.
Paclitaxel-induced peripheral neuropathy is a significant clinical problem can markedly deteriorate patient's quality of life (QoL). Preclinical evidence exists about the preventive capacity of cilostazol against peripheral neuropathy. However, this hypothesis has not yet been clinically investigated. This proof-of-concept study evaluated the effect of cilostazol on the incidence of paclitaxel-induced peripheral neuropathy in patients with non-metastatic breast cancer.
This is a parallel randomized placebo-controlled trial.
The Oncology Center at Mansoura University, Egypt.
Patients with breast cancer scheduled to receive paclitaxel 175 mg/m biweekly.
Patients were randomized to either cilostazol group who received cilostazol tablets 100 mg BID, or to control group who received placebo instead.
The primary endpoint was the incidence of paclitaxel-induced neuropathy evaluated through common terminology criteria for adverse event (NCI-CTCAE) version 4. Secondary endpoints included assessment of the patient's QoL by the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT-GOG-NTx) subscale. Exploratory outcome measures included changes in serum levels of biomarkers namely nerve growth factor (NGF), and neurofilament light chain (NfL).
The incidence of grade 2 and 3 peripheral neuropathies were significantly lower in the cilostazol group (40%) compared to the control group (86.7%) (p < 0.001). The incidence of clinically significant worsening in neuropathy-related QoL was higher in control group compared to the cilostazol group (p = 0.001). A higher percent increase from baseline in serum NGF was observed in the cilostazol group (p = 0.043). The circulating levels of NfL deemed comparable between the two arms at the end of the study (p = 0.593).
Adjunctive use of cilostazol is as a novel option that might reduce the incidence of paclitaxel-induced peripheral neuropathy and improve the patients' QoL. Future larger clinical trials are warranted to confirm these findings.
紫杉醇引起的周围神经病变是一个严重的临床问题，可显著降低患者的生活质量（QoL）。已有临床前证据表明西洛他唑具有预防周围神经病变的作用。然而，这一假设尚未得到临床研究的证实。本概念验证研究评估了西洛他唑对非转移性乳腺癌患者紫杉醇引起的周围神经病变发生率的影响。
这是一项平行随机安慰剂对照试验。
埃及曼苏拉大学肿瘤中心。
计划接受每周两次 175mg/m 紫杉醇治疗的乳腺癌患者。
患者被随机分为西洛他唑组，给予西洛他唑片 100mg，每日 2 次；或对照组，给予安慰剂。
主要终点是通过不良事件通用术语标准（NCI-CTCAE）第 4 版评估紫杉醇引起的神经病变的发生率。次要终点包括通过功能性评估癌症治疗/妇科肿瘤学组神经毒性（FACT-GOG-NTx）量表评估患者的生活质量。探索性结果测量包括血清生物标志物神经生长因子（NGF）和神经丝轻链（NfL）水平的变化。
西洛他唑组（40%）2 级和 3 级周围神经病变的发生率明显低于对照组（86.7%）（p<0.001）。与西洛他唑组相比，对照组神经病变相关生活质量恶化的发生率更高（p=0.001）。西洛他唑组血清 NGF 从基线的百分比升高幅度更高（p=0.043）。研究结束时，两组血清 NfL 水平相当（p=0.593）。
辅助使用西洛他唑是一种新的选择，可能降低紫杉醇引起的周围神经病变的发生率，提高患者的生活质量。需要进一步的大型临床试验来证实这些发现。
