{
  "abstract": "Abstract Objective To evaluate whether methylcobalamin could effectively and safely prevent hand-foot syndrome in patients with human epidermal growth factor receptor 2 (HER2) negative early breast cancer receiving adjuvant capecitabine treatment.Design Multicentre, double blind, randomised, placebo controlled, phase 3 trial.Setting Seven hospitals in China between January 2022 and February 2024.Participants Women aged 18-75 years with pathologically confirmed HER2 negative early breast cancer who were scheduled to receive adjuvant capecitabine treatment.Interventions Eligible patients were randomly assigned in a 1:1 ratio to receive methylcobalamin at a dose of 0.5 mg orally, three times daily, or a placebo for a maximum of 24 weeks.Main outcome measures The primary endpoint was the incidence of grade ≥2 hand-foot syndrome occurring for the first time during capecitabine treatment in the intention-to-treat analysis.Results 234 patients were randomly assigned to receive methylcobalamin (n=117) or placebo (n=117) and were included in the intention-to-treat and safety analysis. Grade ≥2 hand-foot syndrome occurred in 17 (14.5%) of 117 patients in the methylcobalamin group and 34 (29.1%) of 117 patients in the placebo group (risk difference −14.5%, 95% confidence interval −24.9% to −4.1%; one sided P value=0.003). The rate of reduction or discontinuation of capecitabine treatment because of hand-foot syndrome was 7.7% (9 of 117) in the methylcobalamin group and 13.7% (16 of 117) in the placebo group (risk difference −6.0%, 95% confidence interval −13.9% to 1.9%). The two groups showed similar incidence of any other adverse events (88 (75.2%) in the methylcobalamin group and 95 (81.2%) in the placebo group). No methylcobalamin specific adverse events were observed.Conclusions Oral methylcobalamin significantly lowered the severity of hand-foot syndrome by reducing the incidence of grade ≥2 symptoms without unexpected safety concerns in women with HER2 negative early breast cancer who were receiving adjuvant capecitabine treatment. The findings support the use of methylcobalamin to prevent capecitabine associated severe hand-foot syndrome in this patient population.Trial registration ClinicalTrials.gov NCT05165069.",
  "authors": [
    {
      "affiliations": [
        "Guangdong Provincial Key Laboratory of Malignant Tumour Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China",
        "Breast Tumour Centre, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China"
      ],
      "name": "Yuan Xia"
    },
    {
      "affiliations": [
        "Clinical Research Design Division, Clinical Research Centre, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China"
      ],
      "name": "Yingying Zhu"
    },
    {
      "affiliations": [
        "Clinical Research Design Division, Clinical Research Centre, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China",
        "Department of Medical Statistics, School of Public Health, Sun Yat-sen University, Guangzhou, China"
      ],
      "name": "Li Ling"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Centre for Cancer, Sun Yat-sen University Cancer Centre, Guangzhou, China"
      ],
      "name": "Fei Xu"
    },
    {
      "affiliations": [
        "Guangdong Provincial Key Laboratory of Malignant Tumour Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China",
        "Breast Tumour Centre, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China"
      ],
      "name": "Yaping Yang"
    },
    {
      "affiliations": [
        "Department of Breast Oncology, the First People's Hospital of Zhaoqing, Zhaoqing, China"
      ],
      "name": "Jinhui Ye"
    },
    {
      "affiliations": [
        "Department of Breast Surgery, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China"
      ],
      "name": "Weige Tan"
    },
    {
      "affiliations": [
        "Clinical Research Design Division, Clinical Research Centre, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China"
      ],
      "name": "Zouxiang Chen"
    },
    {
      "affiliations": [
        "Guangdong Provincial Key Laboratory of Malignant Tumour Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China",
        "Breast Tumour Centre, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China"
      ],
      "name": "Qiang Liu"
    },
    {
      "affiliations": [
        "Department of Breast and Thyroid Surgery, Peking University Shenzhen Hospital, Shenzhen, China"
      ],
      "name": "Wei Wei"
    },
    {
      "affiliations": [
        "Department of Breast and Thyroid, Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, China"
      ],
      "name": "Jun Zhang"
    },
    {
      "affiliations": [
        "Department of Breast Surgery, Dongguan People's Hospital, Dongguan, China"
      ],
      "name": "Ailing Zhang"
    },
    {
      "affiliations": [
        "Department of Breast Surgery, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China"
      ],
      "name": "Lehong Zhang"
    },
    {
      "affiliations": [
        "Guangdong Provincial Key Laboratory of Malignant Tumour Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China",
        "Breast Tumour Centre, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China"
      ],
      "name": "Erwei Song"
    },
    {
      "affiliations": [
        "Guangdong Provincial Key Laboratory of Malignant Tumour Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China",
        "Breast Tumour Centre, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China"
      ],
      "name": "Chang Gong"
    }
  ],
  "title": "Effect of methylcobalamin on capecitabine induced hand-foot syndrome in patients with HER2 negative early breast cancer: multicentre, double blind, randomised, placebo controlled, phase 3 trial",
  "uid": "89c2bcc2-3f76-56f0-832b-1992d43261ca"
}