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.

Methods

Multicentre, double blind, randomised, placebo controlled, phase 3 trial.

多中心、双盲、随机、安慰剂对照的III期试验。

Seven hospitals in China between January 2022 and February 2024.

2022年1月至2024年2月期间，中国七家医院。

Women aged 18-75 years with pathologically confirmed HER2 negative early breast cancer who were scheduled to receive adjuvant capecitabine treatment.

年龄在18至75岁之间，经病理确认为HER2阴性的早期乳腺癌女性患者，计划接受辅助卡培他滨治疗。

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.

符合条件的患者按1:1的比例随机分配，接受甲钴胺0.5毫克口服，每日三次，或安慰剂，最长治疗24周。

The primary endpoint was the incidenceof grade ≥2 hand-foot syndrome occurring for the first time during capecitabine treatment in the intention-to-treatanalysis.

主要终点是卡培他滨治疗期间首次出现2级或更高级别的手足综合征的发生率，在意向治疗分析中进行评估。

Results

234 patients were randomly assigned to receive methylcobalamin (n=117) or placebo (n=117) and were included in the intention-to-treatand safety analysis.

234名患者被随机分配接受甲钴胺（n=117）或安慰剂（n=117），并被纳入意向治疗和安全性分析。

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).

在甲钴胺组的117名患者中，有17名（14.5%）出现了2级或更高级别的手足综合征，在安慰剂组的117名患者中，有34名（29.1%）出现了2级或更高级别的手足综合征（风险差异-14.5%，95%置信区间-24.9%至-4.1%；单侧P值=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%).

由于手足综合征导致卡培他滨治疗减少或停药的比率在甲钴胺素组为7.7%（117人中有9人），而在安慰剂组为13.7%（117人中有16人）（风险差异-6.0%，95%置信区间-13.9%至1.9%）。

The two groups showed similar incidenceof any other adverse events (88 (75.2%) in the methylcobalamin group and 95 (81.2%) in the placebo group).

两组在其他任何不良事件的发生率上相似（甲钴胺素组有88人（75.2%），安慰剂组有95人（81.2%））。

No methylcobalamin specific adverse events were observed.

未观察到甲钴胺特异性不良事件。

Conclusions

Oral methylcobalamin significantly lowered the severity of hand-foot syndrome by reducing the incidenceof grade ≥2 symptoms without unexpected safety concerns in women with HER2 negative early breast cancer who were receiving adjuvant capecitabine treatment.

口服甲钴胺显著降低了手足综合征的严重程度，通过减少2级及以上症状的发生率，且在使用辅助卡培他滨治疗的HER2阴性早期乳腺癌女性患者中，没有出现意外的安全问题。

The findings support the use of methylcobalamin to prevent capecitabine associated severe hand-foot syndrome in this patient population.

研究结果支持在这一患者群体中使用甲钴胺预防卡培他滨相关的严重手足综合征。

trial_registration

ClinicalTrials.gov NCT05165069.

ClinicalTrials.gov NCT05165069。