Ganglioside-monosialic acid (GM1) prevents oxaliplatin-induced peripheral neurotoxicity in patients with gastrointestinal tumors

Abstract

BackgroundOxaliplatin, an effective antineoplastic agent againstgastrointestinal tumors, can cause severe peripheral neurotoxicity, which seriously limits its clinical application. To date, there are no effective treatments for this complication. Ganglioside-monosialic acid (GM1) has been shown to protect neurons against injuries and degeneration. The aim of this study was to evaluate the effects of GM1 on preventing oxaliplatin-induced neurotoxicity in patients with gastrointestinal tumors.MethodsIn this study, 120 patients with gastrointestinal tumors were enrolled, andthey received the treatment of XELOX (oxaliplatin and capecitabine) and FOLFOX4 (oxaliplatin, leukovolin and 5-fluorouracil). The patients were randomly divided into two groups, the experimental group and control group, with60 patients ineach. On the day chemotherapy was initiated, the experimental group received GM1 intravenously (100 mg once daily) for 3 days, while no neuroprotective agents were applied in the control group. The incidence rates and classification of neurotoxicity in the two groups were evaluated and the differences between the two groups were examined. Furthermore, whether GM1 affected the therapeutic effects of chemotherapy was also examined.ResultsThe grade of neurotoxicity in the experimental group was significantly lower than in the control group (P<0.05, Mann–Whitney U test). The probability of occurrence of low-grade neurotoxicity (grade 0 and 1) in the experimental group was higher than that in the control group (logistic ordinal regression); whereas the probability of occurrence of high-grade neurotoxicity (grade 2 and 3) in the experimental group was lower than in the control group (logistic ordinal regression).ConclusionThe data suggested that GM1 could reduce the grade of oxaliplatin-induced neurotoxicity and was an effective neuroprotective agent against oxaliplatin-induced high-grade neurotoxicity in patients with gastrointestinal tumors.

Protection against Experimental Stroke by Ganglioside GM1 Is Associated with the Inhibition of Autophagy

“…Although the development of the acute inflammatory polyneuropathy Guillain-Barre´ syndrome (GBS) following intravenous ganglioside treatment resulted in the withdrawal of GM1 from European market [ 31 ], this adverse effect was shown to be rare, and the relationship between exogenous gangliosides and GBS remains controversial [ 32 , 33 ]. These drugs are still available and have been extensively prescribed in other markets including China, where a multitude of neurological maladies have been treated with gangliosides in the absence of resultant GBS or other severe adverse events [ 34 – 37 ]. In a trail conducted by Schneider et al ., a 5-year clinical course confirmed the long-term safety of GM1 therapy and suggested favorable efficacy for Parkinson's disease patients [ 35 ].…”

Ganglioside Monosialic Acid Alleviates Peripheral Neuropathy Induced by Utidelone Plus Capecitabine in Metastatic Breast Cancer From a Phase III Clinical Trial

“…Notably, GM1, a kind of glycosphingolipid, was reported to effectively decrease the incidence of cumulative grade 3 oxaliplatin- and taxane-induced neurotoxicity in a non-randomized and retrospective study. However, no effect on acute, cold-induced neurotoxicity was found ( 12 , 13 ). No substantial differences in permanent discontinuation of chemotherapy and effects on survival were noted between GM1 and control.…”

Neurotrophic effects of GM1 ganglioside, NGF, and FGF2 on canine dorsal root ganglia neurons in vitro

“…There is evidence that application of monosialotetrahexosylganglioside (G M1 ) has therapeutic potential, for example in the treatment of acute spinal cord injury 18,19 . In addition, clinical trials demonstrated that G M1 has symptomatic and disease modifying effects on different human neurodegenerative diseases [20][21][22] . Several studies in rodents have demonstrated that the neuroprotective effect of G M1 seems to be dependent on the interaction with .…”