中山大学孙逸仙纪念医院龚畅团队近日研究了甲基钴胺对HER2阴性早期癌症患者卡培他滨诱导的手足综合征的影响：多中心、双盲、随机、安慰剂对照、3期试验。2025年9月11日出版的《英国医学杂志》发表了这项成果。

为了评价甲基钴胺素是否能有效、安全地预防接受卡培他滨辅助治疗的人表皮生长因子受体2 （HER2）阴性早期乳腺癌患者的手足综合征，研究组进行了一项多中心，双盲，随机，安慰剂对照，的3期临床试验。2022年1月至2024年2月期间，在中国7家医院招募18-75岁病理证实HER2阴性早期乳腺癌的女性计划接受卡培他滨辅助治疗。

符合条件的患者以1:1的比例随机分配接受甲基钴胺素0.5 mg口服，每日3次，或安慰剂，最长为24周。在意向治疗分析中，主要终点是卡培他滨治疗期间首次发生≥2级手足综合征的发生率。

234名患者被随机分配接受甲钴胺素（n=117）或安慰剂（n=117）治疗，并被纳入意向治疗和安全性分析。甲钴胺组117例患者中有17例（14.5%）出现≥2级手足综合征，安慰剂组117例患者中有34例（29.1%）出现≥2级手足综合征（风险差异为14.5%，95%可信区间为24.9% ~ 4.1%，单侧P值=0.003）。甲钴胺组因手足综合征减少或停止卡培他滨治疗的比率为7.7%（117人中的9人），安慰剂组为13.7%（117人中的16人）（风险差异为6.0%，95%可信区间为13.9% ~ 1.9%）。两组其他不良事件发生率相似（甲钴胺组88例（75.2%），安慰剂组95例（81.2%））。未观察到甲钴胺特异性不良事件。< br / > < br / >

研究结果表明，在接受卡培他滨辅助治疗的HER2阴性早期乳腺癌患者中，口服甲钴胺素通过降低≥2级症状的发生率而显著降低了手足综合征的严重程度。研究结果支持使用甲基钴胺素预防卡培他滨相关的严重手足综合征。

附：英文原文

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

Author: Yuan Xia, Yingying Zhu, Li Ling, Fei Xu, Yaping Yang, Jinhui Ye, Weige Tan, Zouxiang Chen, Qiang Liu, Wei Wei, Jun Zhang, Ailing Zhang, Lehong Zhang, Erwei Song, Chang Gong

Issue&Volume: 2025/09/11

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.

DOI: 10.1136/bmj-2025-084290

Source: https://www.bmj.com/content/390/bmj-2025-084290