The Effects of Ganglioside-Monosialic Acid in Taxane-Induced Peripheral Neurotoxicity in Patients With Breast Cancer

A Randomized Trial

Yanhong Su; Jiajia Huang; Shusen Wang; Joseph M. Unger; Jonathan Arias-Fuenzalida; Yanxia Shi; Jibin Li; Yongxiang Gao; Wei Shi; Xinyue Wang; Roujun Peng; Fei Xu; Xin An; Cong Xue; Wen Xia; Ruoxi Hong; Yongyi Zhong; Ying Lin; Heng Huang; Anqin Zhang; Lehong Zhang; Li Cai; Jinxin Zhang; Zhongyu Yuan


J Natl Cancer Inst. 2020;112(1):55-62. 

In This Article

Abstract and Introduction


Background: Taxane-induced peripheral neuropathy (TIPN) is a dose-limiting adverse effect. Ganglioside-monosialic acid (GM1) functions as a neuroprotective factor. We assessed the effects of GM1 on the prevention of TIPN in breast cancer patients.

Methods: We conducted a randomized, double-blind, placebo-controlled trial including 206 patients with early-stage breast cancer planning to receive taxane-based adjuvant chemotherapy with a follow-up of more than 1 year. Subjects were randomly assigned to receive GM1 (80 mg, day −1 to day 2) or placebo. The primary endpoint was the Functional Assessment of Cancer Treatment Neurotoxicity subscale score after four cycles of chemotherapy. Secondary endpoints included neurotoxicity evaluated by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 and the Eastern Cooperative Oncology Group neuropathy scale. All statistical tests were two-sided.

Results: In 183 evaluable patients, the GM1 group reported better mean Functional Assessment of Cancer Treatment Neurotoxicity subscale scores than patients in the placebo group after four cycles of chemotherapy (43.27, 95% confidence interval [CI] = 43.05 to 43.49 vs 34.34, 95% CI = 33.78 to 34.89; mean difference = 8.96, 95% CI = 8.38 to 9.54, P < .001). Grade 1 or higher peripheral neurotoxicity in Common Terminology Criteria for Adverse Events v4.0 scale was statistically significantly lower in the GM1 group (14.3% vs 100.0%, P < .001). Additionally, the GM1 group had a statistically significantly lower incidence of grade 1 or higher neurotoxicity assessed by Eastern Cooperative Oncology Group neuropathy scale sensory neuropathy (26.4% vs 97.8%, P < .001) and motor neuropathy subscales (20.9% vs 81.5%, P < .001).

Conclusions: The treatment with GM1 resulted in a reduction in the severity and incidence of TIPN after four cycles of taxane-containing chemotherapy in patients with breast cancer.


Taxane is one of the most widely used anticancer drugs in the treatment of breast cancer. Although taxane plays key roles in reducing the recurrence in early-stage breast cancer and improving the outcomes of advanced breast cancer patients, it causes a variety of side effects. Among them, taxane-induced peripheral neuropathy (TIPN) is a dose-limiting adverse effect leading to early treatment discontinuation.[1,2]

Taxane is an antimicrotubule anticancer agent that induces cell apoptosis by stabilizing microtubules and inducing a sustained mitotic block at the metaphase-anaphase boundary.[3,4] Although several studies suggest taxane causes damage to peripheral nerves by inhibiting anterograde and retrograde axonal transport, the mechanism of TIPN remains unclear.[5] The reported incidence of TIPN in breast cancer patients is variable.[6,7] The degree of neurotoxicity is related to the disease type, taxane dosage, magnitude of the administered taxane dose, drug combination, and individual patient characteristics.[8–11] Symptoms of TIPN are largely reversible, and most patients recover within the first year after chemotherapy. Although persistent TIPN negatively affects long-term quality of life, the severity is usually low and well tolerated.[6,12,13] However, patients who suffer from severe TIPN are more likely to decrease the taxane dose or discontinue treatment, receiving less cumulative chemotherapy than planned.[14–17] Thus, effective strategies for the prevention of TIPN are urgently needed.

Ganglioside-monosialic acid (GM1) is a monosialo-glycosphingolipid and belongs to the family of gangliosides, which are unique acidic glycolipids comprising sphingosine, fatty acid, and sialic acid. GM1 performs an important function in the processes of neurogenesis, nerve development and differentiation, cell recognition, and signal transduction.[18,19] In injured nerve cells, exogenous GM1 promotes neurotrophic activity and the recovery of neuritic processes.[20] In vitro experiments indicate that incorporation of taxanes in ganglioside micelles did not impair their uptake or biological effect. Preclinical animal models suggested that porcine GM1 may be effective in the prevention and treatment of paclitaxel-induced neuropathy.[21] A phase II clinical trial showed that GM1 could safely reduce the severity of oxaliplatin-induced neurotoxicity in patients with gastrointestinal tumors.[22] The above observations suggest that GM1 could have a positive impact on the treatment of TIPN. The purpose of this trial was to evaluate the effect of GM1 in the prevention of TIPN in breast cancer patients.