Department of Anesthesiology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, P. R. China.
Department of Anesthesiology, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510289, P. R. China.
BMC Cancer. 2021 Nov 2;21(1):1173. doi: 10.1186/s12885-021-08884-4.
Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect that largely remains an unresolved clinical issue, leading to long-term morbidity. This meta-analysis aimed to evaluate the efficacy and safety of Ganglioside-monosialic acid (GM1) in preventing CIPN.
Systematic literature searches of PubMed, Web of Science, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were performed to identify randomized controlled trials and cohort studies that evaluated the efficacy of GM1 for preventing CIPN. Conventional meta-analysis with a random-effects model and trial sequential analysis (TSA) were performed.
A total of five studies involving 868 participants were included. The results showed that GM1 did not reduce the overall incidence of grade ≥ 2 CIPN when the common terminology criteria for adverse events (CTCAE) was used (OR 0.34, 95% CI 0.34-1.11). Subgroup analyses showed that GM1 could not reduce the risk of CTCAE grade ≥ 2 CIPN (OR 0.63, 95% CI 0.35-1.13) and neurotoxicity criteria of Debiopharm (DEB-NTC) grade ≥ 2 CIPN (OR 0.25, 95% CI 0.01-7.10) in oxaliplatin-treated patients, despite that GM1 was associated with a reduced risk of CTCAE grade ≥ 2 CIPN in the taxane subgroup of one study (OR 0.003, 95% CI 0.00-0.05). These results were confirmed by the sub-analysis of randomized controlled trials (RCTs). In TSA, the z-curve for the taxane subgroup crossed the upper trial sequential monitoring boundary (TSMB) but do not reach the required information size (RIS). The z-curves for the oxaliplatin subgroup remained in the nonsignificant area and did not reach the RIS. Further, GM1 did not influence the rate of response to chemotherapy and CTCAE grade ≥ 2 adverse events such as fatigue, nausea, diarrhea, and rash.
GM1 seemed to be well-tolerated and did not influence the anti-cancer effects of chemotherapeutic agents. Although the data did not confirm the effectiveness of GM1 in preventing oxaliplatin-induced peripheral neuropathy, GM1 might be able to prevent taxane-induced peripheral neuropathy. More studies are required in different ethnic populations receiving taxane-based chemotherapy to confirm these findings.
化疗引起的周围神经病变（CIPN）是一种剂量限制的副作用，在很大程度上仍是一个未解决的临床问题，导致长期发病。本荟萃分析旨在评估神经节苷脂单唾液酸（GM1）预防 CIPN 的疗效和安全性。
系统检索 PubMed、Web of Science、Embase、Cochrane 对照试验中心注册库和 ClinicalTrials.gov，以确定评估 GM1 预防 CIPN 疗效的随机对照试验和队列研究。采用随机效应模型进行常规荟萃分析和试验序贯分析（TSA）。
共纳入 5 项研究，涉及 868 名参与者。结果显示，采用常见不良事件术语标准（CTCAE）时，GM1 并未降低 CIPN 总发生率≥2 级（OR 0.34，95%CI 0.34-1.11）。亚组分析显示，GM1 不能降低奥沙利铂治疗患者 CTCAE 分级≥2 级 CIPN（OR 0.63，95%CI 0.35-1.13）和 Debiopharm 神经毒性标准（DEB-NTC）分级≥2 级 CIPN（OR 0.25，95%CI 0.01-7.10）的风险，尽管 GM1 与一项研究的紫杉烷亚组 CTCAE 分级≥2 级 CIPN 风险降低相关（OR 0.003，95%CI 0.00-0.05）。这些结果在随机对照试验（RCT）的亚组分析中得到了证实。在 TSA 中，紫杉烷亚组的 z 曲线穿过了上试验序贯监测边界（TSMB），但未达到所需信息大小（RIS）。奥沙利铂亚组的 z 曲线仍处于非显著区域，且未达到 RIS。此外，GM1 并未影响化疗的反应率和 CTCAE 分级≥2 级不良事件（如疲劳、恶心、腹泻和皮疹）的发生率。
GM1 似乎耐受性良好，且不影响化疗药物的抗癌作用。尽管数据并未证实 GM1 预防奥沙利铂诱导的周围神经病变的有效性，但 GM1 可能能够预防紫杉烷诱导的周围神经病变。需要在接受紫杉烷类化疗的不同种族人群中开展更多研究来证实这些发现。
