A randomized, double-blind, placebo-controlled study from Thailand reports a significant reduction in the incidence of chemotherapy-induced peripheral neuropathy (CIPN) among patients with gynaecological cancers treated with neurotoxic chemotherapy who received vitamin B12 supplementation vs placebo.
Gynaecological cancers are often treated with neurotoxic chemotherapy, with the incidence of CIPN reported at 50–80 percent. [BMC Cancer 2006;6:5; Gynecol Oncol 2021;163:578-582] Various agents, including amifostine, glutathione, vitamin E, intravenous calcium or magnesium infusions, anticonvulsants, antidepressants, and selective serotonin reuptake inhibitors, have been studied as CIPN prophylactics, however, none have demonstrated a strong clinical benefit. While the American Society of Clinical Oncology’s (ASCO) guidelines recommend duloxetine to treat established painful CIPN, its efficacy in preventing CIPN has not been established. [J Clin Oncol 2025;doi:10.1200/JCO.2025.43.16_suppl.12010]
“In clinical practice, some physicians prescribe oral vitamin B to treat peripheral neuropathy, including CIPN, due to its known benefits for the nervous system,” wrote the researchers. Vitamin B12, in particular, supports nerve regeneration by promoting nerve cell survival, remyelination, and maintenance of myelin sheaths – functions that are often impaired in patients with CIPN. It is also low-cost, widely available and has low toxicity. [Asian Pac J Cancer Prev 2026;27:1747-1756]
While the standard guideline for treating vitamin B12 deficiency recommends 1,000 mcg of intramuscular (IM) hydroxocobalamin three times weekly for 2 weeks, followed by maintenance every 3 months for life, IM injections are time-consuming for patients and caregivers and increase healthcare costs. [Br J Haematol 2014;166:496-513] “Thus, we administered 500 mcg of vitamin B12, with two tablets taken twice daily after meals in the intervention group of our study,” explained the researchers. [Cochrane Database Syst Rev 2005;3:Cd004655]
Forty patients (mean age, 49.9 years) with gynaecological cancers (ovarian/fallopian tube, endometrial, cervical, or synchronous) treated with taxane-based combinations with either carboplatin or cisplatin were randomized to receive vitamin B12 or placebo (n=20) from the start of chemotherapy until 4 weeks after completing six cycles. Although 15 percent of patients had diabetes, none showed signs of peripheral neuropathy before chemotherapy.
According to generalized linear mixed-model analysis, the incidence of CIPN was 5 percent in the vitamin B12 group vs 20 percent in the placebo group (odds ratio [OR], 0.21; 95 percent confidence interval [CI], 0.07–0.66). “After adjusting for age, cancer type, stage, and treatment modalities, vitamin B12 reduced CIPN risk by 96 percent compared with placebo [OR, 0.04; 95 percent CI, 0.01–0.29],” highlighted the researchers.
While no significant differences were found in the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group–Neurotoxicity (FACT/GOG-Ntx) scores between the two groups, the researchers observed a trend for increasing difference in FACT/GOG-Ntx scores during later chemotherapy cycles, which is likely due to CIPN exacerbating in a time- and dose-dependent manner. “Almost all CIPN cases in our study emerged by the third chemotherapy cycle, suggesting that preventive strategies should ideally start at the first or second cycle,” recommended the researchers.
There were no differences in the incidence of adverse events between the vitamin B12 and placebo groups.
“The present study suggests that oral vitamin B12 may reduce the incidence of CIPN in gynaecological cancer patients undergoing neurotoxic chemotherapy, supporting its potential as a preventive measure for CIPN in this clinical setting,” summarized the researchers. “To confirm this efficacy, future investigations should include larger, multicentre randomized controlled trials with adequate sample sizes to enhance generalizability and statistical precision.”