Oxaliplatin-induced neurotoxicity is a common, potentially severe and dose-limiting adverse effect of cancer treatment . The characteristics of oxaliplatin-induced neurotoxicity are related to dose intensity and cumulative dose. Neurotoxicity can profoundly affect the qualityoflife, often compelling clinicians to lower the chemotherapy regimen, consequently limiting therapeutic efficacy . Oxaliplatin-induced neuropathy is of two types: acute and chronic. Acute neuropathy was believed to reflect a state of peripheral nerve hyperexcitability that likely represents a transient oxaliplatin-induced impairment of ion channels, while the chronic treatment induces an axonal neuropathy similar to the other platinum-based drugs . Strategies to ameliorate oxaliplatin neurotoxicity include the use of several ‘neuroprotective’ drugs, such as reduced glutathione , amifostine , andcalcium and magnesium infusion. . GM1 is used in the treatment of peripheral neuropathy such as diabetic peripheral neuropathy in preclinical animal models, owingto its superior neuroprotective effects and function of nerve repair. To our knowledge, the clinical use of GM1 in the prevention of oxaliplatin-induced neurotoxicity has not yet been investigated.
Four of the enrolled patients (3.33%) presented with dyspnea, which was a little higher than that of a previous study (1 to 2%) . The dyspnea of these four patients was relieved by symptomatic treatment and they underwent complete chemotherapy after intravenous drip was slowed. Only one patient developed dyspnea again when undergoing chemotherapy and the other three patients did not develop symptoms of dyspnea again. It is reported that multi-infusion and prolongation of the infusion time could reduce the neurotoxicity of oxaliplatin [33, 34]. The dyspnea that occurred in the patients may be associated with the rapid infusion of oxaliplatin. Whether GM1 has causative or therapeutic effects on dyspnea is not clearand the effects of GM1 on dyspnea induced by oxaliplatin should be observed in a clinical trial of a sufficiently larger sample size.
Two patients who underwent surgery after chemotherapy presented with postoperative aggravation of neurotoxicity, which was consistent with previous reports that surgery could aggravate neurotoxicity induced by oxaliplatin . In the control group, one patient receiving the cumulative dose of oxaliplatin of 1800 mg (1065.09 mg/m2) presented with torpid reaction, loss of memory and grade 3 neurotoxicity. The results obtained by Lehky showed that rare neurotoxicity such as urine retention, Lhermitte’s sign and reversible posterior leukoencephalopathy syndrome could occur when the cumulative dose of oxaliplatin exceeded 1000 mg per patient . Twenty-five percent of patients exhibited decreased visual acuity and/or hypogeusia. There was no significant difference in the incidence rates of decreased visual acuity and/or hypogeusia between the two groups, suggesting that GM1 could not prevent the toxic effects of oxaliplatin on vision and taste receptors.
In our study, the total incidence of neurotoxicity in the experimental group was 68.33%, while that in the control group was 78.33%. However, the grade of neurotoxicity in the experimental group was significantly lower than in the control group (P = 0.021). Notably, the probability of occurrence of high-grade (grade 2 and 3) neurotoxicity in the experimental group was lower than in the control group (Table 6). There were significant differences in the probability of occurrence of neurotoxicity between the two groups (P = 0.041, χ2 test) and the probability of occurrence of grade 3 neurotoxicity was significantly lower in the experimental group than in the control group (P = 0.005, χ2 test). In the experimental group, six patients did not present with neurotoxicity during treatment. However, they presented with grade 2 or 3 neurotoxicity 1 to 3 months after chemotherapy. We speculated that this phenomenon was due to the short-term application of GM1. Owing to limited length of stay, the usage time of GM1 per patient was only 3 days in this study, leading to only partially preventive effects of GM1 exerted on patients.
In this study, the drugs which were used to prevent oxaliplatin-induced neurotoxicity mostly exhibited limited efficacy. Notably, calcium and magnesium infusion was reported to effectively decrease the incidence of chronic, cumulative, grade 2 or greater oxaliplatin-induced neurotoxicity in a non-randomized and retrospective study (P = 0.038). However, no effect on acute, cold-induced neurotoxicity was found. No substantial differences in adverse effects were noted between calcium/magnesium and placebo. Comparing the results from these trials may be difficult or impossible because of the use of different dosages and regimens of treatment, and the lack of standardization of the methods used in evaluating the extent or the incidence of neurotoxicity.