The Effects of Ganglioside-Monosialic Acid in Taxane-induced Peripheral Neurotoxicity in Patients with Breast Cancer: A Randomized Trial.

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 randomized to receive GM1 (80 mg, Day -1 to Day 2) or placebo. The primary endpoint was the Functional Assessment of Cancer Treatment Neurotoxicity (FACT-Ntx) subscale score after 4-cycles of chemotherapy. Secondary endpoints included neurotoxicity evaluated by CTCAE Version 4.0 and the Eastern Cooperative Oncology Group neuropathy scale (ENS). All statistical tests were two-sided. RESULTS In 183 evaluable patients, GM1 group reported better mean FACT-Ntx subscale scores than patients in the placebo group after 4-cycles of chemotherapy (43.27 [95% 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 peripheral neurotoxicity in CTCAE v4.0 scale was statistically significantly lower in GM1 group (14.3% vs 100.0%, P < .001). Additionally, GM1 group reported a statistically significantly lower incidence of grade ≥ 1 neurotoxicity assessed by ENS 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 4-cycles of taxane-containing chemotherapy in patients with breast cancer.