Open AccessPhase III randomized, placebo‐controlled, double‐blind study of monosialotetrahexosylganglioside for the prevention of oxaliplatin‐induced peripheral neurotoxicity in stage II/III colorectal cancer
Author(s) -
Wang Deshen,
Wang Zhiqiang,
Chen Gong,
Peng Jiewen,
Wang Wei,
Deng Yanhong,
Wang Fenghua,
Zhang Jianwei,
Liang Hanlin,
Feng Fen,
Xie Chuanbo,
Ren Chao,
Jin Ying,
Shi Simei,
Fan Wenhua,
Lu Zhenhai,
Ding Peirong,
Wang Feng,
Xu Ruihua,
Li Yuhong
Publication year - 2020
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.2693
Subject(s) - oxaliplatin , medicine , neurotoxicity , folfox , peripheral neuropathy , placebo , gastroenterology , adverse effect , clinical endpoint , chemotherapy , colorectal cancer , anesthesia , surgery , randomized controlled trial , cancer , toxicity , pathology , endocrinology , alternative medicine , diabetes mellitus
Background Monosialotetrahexosylganglioside ( GM 1) 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 m FOLFOX 6 were randomly assigned to intravenous GM 1 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 ‐ CIPN 20), 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 ( GM 1: 33.7% vs placebo: 31.6%; P = .76) or neuropathy measured by the EORTC QLQ ‐ CIPN 20 or time to grade 2 neurotoxicity using NCI ‐ CTCAE and the oxaliplatin‐specific neuropathy scale. GM 1 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 GM 1 and placebo arms, respectively ( P = .19). There were no differences in toxicity between the arms. Conclusion Patients receiving GM 1 were less troubled by the symptoms of acute neuropathy. However, we do not support the use of GM 1 to prevent cumulative neurotoxicity. ( ClinicalTrials.gov number, NCT02251977).