Abstract：
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/m2 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.
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/m2 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.
摘要：
背景：紫杉醇引起的周围神经病变是一个重要的临床问题，可显著降低患者的生活质量（QoL）。临床前证据表明西洛他唑具有预防周围神经病变的能力。然而,这一假设尚未进行临床研究.这项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诱导的周围神经病变发生率的影响。
方法：本研究是一项平行随机安慰剂对照试验。计划每两周接受紫杉醇175mg/m2的乳腺癌患者（n=69）被随机分配到接受西洛他唑100mgBID片剂的西洛他唑组，或接受安慰剂的对照组。主要终点是通过常见的不良事件术语标准（NCI-CTCAE）第4版评估的紫杉醇诱导的神经病的发生率。次要终点包括通过癌症治疗功能评估/妇科肿瘤学组-神经毒性（FACT-GOG-NTx）子量表评估患者的QoL。探索性结果测量包括血清生物标志物水平的变化，即神经生长因子（NGF），和神经丝轻链(NfL)。
结果：二级发病率，与对照组（86.7％）相比，西洛他唑组（40％）的3种周围神经病变显着降低（P<0.001）。与西洛他唑组相比，对照组的神经病相关QoL临床显着恶化的发生率更高（P=0.001）。在西洛他唑组中观察到血清NGF从基线的更高百分比增加(P=0.043)。在研究结束时,认为两组之间的NfL循环水平相当(P=0.593)。
结论：辅助使用西洛他唑可能被认为是一种新的选择，可以降低紫杉醇诱导的周围神经病变的发生率并改善患者的生活质量。未来更大的临床试验有必要证实这些发现。
方法：本研究是一项平行随机安慰剂对照试验。计划每两周接受紫杉醇175mg/m2的乳腺癌患者（n=69）被随机分配到接受西洛他唑100mgBID片剂的西洛他唑组，或接受安慰剂的对照组。主要终点是通过常见的不良事件术语标准（NCI-CTCAE）第4版评估的紫杉醇诱导的神经病的发生率。次要终点包括通过癌症治疗功能评估/妇科肿瘤学组-神经毒性（FACT-GOG-NTx）子量表评估患者的QoL。探索性结果测量包括血清生物标志物水平的变化，即神经生长因子（NGF），和神经丝轻链(NfL)。
结果：二级发病率，与对照组（86.7％）相比，西洛他唑组（40％）的3种周围神经病变显着降低（P<0.001）。与西洛他唑组相比，对照组的神经病相关QoL临床显着恶化的发生率更高（P=0.001）。在西洛他唑组中观察到血清NGF从基线的更高百分比增加(P=0.043)。在研究结束时,认为两组之间的NfL循环水平相当(P=0.593)。
结论：辅助使用西洛他唑可能被认为是一种新的选择，可以降低紫杉醇诱导的周围神经病变的发生率并改善患者的生活质量。未来更大的临床试验有必要证实这些发现。
