Phase III randomized, placebo-controlled, double-blind study of monosialotetrahexosylganglioside for the prevention of oxaliplatin-induced peripheral neurotoxicity in stage II/III colorectal cancer
Phase III randomized, placebo-controlled, double-blind study of monosialotetrahexosylganglioside for the prevention of oxaliplatin-induced peripheral neurotoxicity in stage II/III colorectal cancer
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单唾液酸四己糖神经节苷脂预防 II/III 期结直肠癌中奥沙利铂诱导的周围神经毒性的 III 期随机、安慰剂对照、双盲研究
DOI：
10.1002/cam4.2693
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发表时间：
2019-11-13
期刊：
影响因子：
4
通讯作者：
Li, Yu-hong
中科院分区：
文献类型：
--
作者：
Wang, De-shen;Wang, Zhi-qiang;Li, Yu-hong
研究背景单唾液酸四己糖神经节苷脂（GM 1）是一种神经保护性鞘糖脂，具有神经修复作用。基于奥沙利铂的化疗具有神经毒性。本研究评估了GM 1在接受奥沙利铂化疗的结直肠癌（CRC）患者中预防奥沙利铂诱导的外周神经毒性（OIPN）的疗效。方法将196例接受mFOLFOX 6辅助化疗的II/III期结直肠癌患者随机分为静脉注射GM 1组和安慰剂组。主要终点为2级或更严重累积神经毒性（NCI-CTCAE）的发生率。次要终点为慢性累积神经毒性（EORTC QLQ-CIPN 20）、至2级神经毒性的时间（NCI-CTCAE或奥沙利铂特异性神经病变量表）、急性神经毒性（模拟量表）、因OIPN而减量或停药的发生率、3年无病生存期（DFS）和不良事件。结果两组之间的NCI-CTCAE 2级或更严重神经毒性（GM 1：33.7% vs安慰剂：31.6%; P = .76）或EORTC QLQ-CIPN 20测量的神经病变或使用NCI-CTCAE和奥沙利铂特异性神经病变量表测量的至2级神经毒性的时间无显著差异。GM 1显著降低了参与者报告的急性神经毒性（对冷物品的敏感性[P <.01]，吞咽冷液体的不适[P <.01]，咽喉不适[P < .01]，肌肉痉挛[P < .01]）。两组之间的剂量减少或停药率无显著差异（P = .08）。GM 1组和安慰剂组的3年DFS率分别为85%和83%（P = 0.19）。两组之间的毒性无差异。结论应用GM 1治疗的急性神经病患者症状轻。但是，我们不支持使用GM 1来预防累积神经毒性。（编号，NCT 02251977）。
Background Monosialotetrahexosylganglioside (GM1) is a neuroprotective glycosphingolipid that repairs nerves. Oxaliplatin-based chemotherapy is neurotoxic. This study assessed the efficacy of GM1 for preventing oxaliplatin-induced peripheral neurotoxicity (OIPN) in colorectal cancer (CRC) patients receiving oxaliplatin-based chemotherapy. Methods In total, 196 patients with stage II/III CRC undergoing adjuvant chemotherapy with mFOLFOX6 were randomly assigned to intravenous GM1 or a placebo. The primary endpoint was the rate of grade 2 or worse cumulative neurotoxicity (NCI-CTCAE). The secondary endpoints were chronic cumulative neurotoxicity (EORTC QLQ-CIPN20), time to grade 2 neurotoxicity (NCI-CTCAE or the oxaliplatin-specific neuropathy scale), acute neurotoxicity (analog scale), rates of dose reduction or withdrawal due to OIPN, 3-year disease-free survival (DFS) and adverse events. Results There were no significant differences between the arms in the rate of NCI-CTCAE grade 2 or worse neurotoxicity (GM1: 33.7% vs placebo: 31.6%; P = .76) or neuropathy measured by the EORTC QLQ-CIPN20 or time to grade 2 neurotoxicity using NCI-CTCAE and the oxaliplatin-specific neuropathy scale. GM1 substantially decreased participant-reported acute neurotoxicity (sensitivity to cold items [P < .01], discomfort swallowing cold liquids [P < .01], throat discomfort [P < .01], muscle cramps [P < .01]). The rates of dose reduction or withdrawal were not significantly different between the arms (P = .08). The 3-year DFS rates were 85% and 83% in the GM1 and placebo arms, respectively (P = .19). There were no differences in toxicity between the arms. Conclusion Patients receiving GM1 were less troubled by the symptoms of acute neuropathy. However, we do not support the use of GM1 to prevent cumulative neurotoxicity. ( number, NCT02251977).