g(m1)-ganglioside and Colorectal-Neoplasms

Monosialotetrahexosylganglioside (GM1) 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.. In total, 196 patients with stage II/III CRC undergoing adjuvant chemotherapy with mFOLFOX6 were randomly assigned to intravenous GM1 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-CIPN20), 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.. There were no significant differences between the arms in the rate of NCI-CTCAE grade 2 or worse neurotoxicity (GM1: 33.7% vs placebo: 31.6%; P = .76) or neuropathy measured by the EORTC QLQ-CIPN20 or time to grade 2 neurotoxicity using NCI-CTCAE and the oxaliplatin-specific neuropathy scale. GM1 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 GM1 and placebo arms, respectively (P = .19). There were no differences in toxicity between the arms.. Patients receiving GM1 were less troubled by the symptoms of acute neuropathy. However, we do not support the use of GM1 to prevent cumulative neurotoxicity. (ClinicalTrials.gov number, NCT02251977).

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Colorectal Neoplasms; Disease-Free Survival; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluorouracil; G(M1) Ganglioside; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Oxaloacetates; Peripheral Nervous System Diseases; Placebos; Severity of Illness Index

Oxaliplatin is a key agent in the treatment of colorectal cancer. However, peripheral neuropathy markedly limits the use of oxaliplatin. This retrospective study was performed to assess the efficacy of monosialotetrahexosylganglioside (GM1) for preventing oxaliplatin induced neurotoxicity. Patients with colorectal cancer treated with oxaliplatin based chemotherapy (FOLFOX or XELOX) were retrospectively divided into two groups according to the use of GM1. The severity of neurotoxicity and efficacy of oxaliplatin were evaluated. A total of 278 cases were included, 114 in GM1 group and 164 in control group. A significantly lower incidence of grade 1-3 acute neurotoxicity (81% vs 92%, p=0.006), grade 2 acute neurotoxicity (26% vs 45%, p=0.002) was observed in GM1 group. Similarly, incidence of grade 1-3 (30% vs 48%, p=0.003) and grade 3 chronic neurotoxicity (4% vs 13%, p=0.021) was also lower in GM1 group. No difference was detected in objective response rate, progress free survival, and median overall survival between GM1 group and control group. The retrospective study demonstrated that GM1 significantly reduced the incidence of oxaliplatin induced neuropathy, especially severe neuropathy, without impairment of efficacy. Prospective trials of GM1 as neuroprotective of oxaliplatin treatment in colorectal cancer are warranted.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Colorectal Neoplasms; Deoxycytidine; Disease-Free Survival; Female; Fluorouracil; G(M1) Ganglioside; Humans; Leucovorin; Male; Middle Aged; Neurotoxicity Syndromes; Organoplatinum Compounds; Oxaliplatin; Oxaloacetates; Retrospective Studies; Severity of Illness Index; Survival Rate; Treatment Outcome

A egg yolk polyclonal IgY has been prepared by immunization of white leghorn chickens with small unilamellar liposomal asialoGM1. The newly prepared anti-asialoGM1 IgY has been characterized to be specific toward the terminal carbohydrate moiety of asialoGM1, and has no cross reactivity to its sialylated counterpart (ganglioside, GM1) as evidenced by immunochromatographic studies. General glycohistochemical methods along with antigen specific lectin and immunohistochemical staining using anti-asialoGM1 IgY were used to study the expression of Thomsen-Friedenreich (T-) disaccharide antigen in human colorectal adenocarcinoma tissues. The expression of T-antigen in colon cancer tissue was detected by two T-disaccharide specific probes, chicken anti-T-yolk antibody (IgY) and Artocarpus integrifolia lectin (AIL) and was found to be more pronounced in both the secreted mucin as well as the cytoplasmic mucin deposits. These immunochemical detection methods for T-antigen showed a weaker correlation with other glycostaining methods using, alcian-blue/periodic acid-Schiff (AB-PAS) and high iron diamine (HID). However, a general enzymatic staining for galactose and galactosamine containing glycoconjugates, by galactose oxidase-Schiff method, showed a good correlation with T-antigen detection. While the T-beta specific anti-asialoGM1 could localize T-antigen in 11 of 13 (84%) human colorectal adenocarcinoma tissue sections tested, the T-alpha specific AIL could localize the T-antigen in only 6 of the tissues (46%). These observations confirm previously reported findings, of the prevalence of T-beta conformation in colon cancer, that binds significantly more with the anti-asialoGM1 IgY than with the T-alpha specific AIL. Hence, both anti-T IgY and the AIL immunohistochemical probes may have useful diagnostic value because of the ease of preparation and cost effectiveness, but the T-beta specific anti-asialoGM1 probe (IgY) would have a better prognostic value in colon adenocarcinomas.

Topics: Adenocarcinoma; Antibodies; Antigens, Tumor-Associated, Carbohydrate; Colorectal Neoplasms; Egg Yolk; G(M1) Ganglioside; Humans; Immunoglobulins; Immunohistochemistry