晚期或转移性乳腺癌卡培他滨疗法相关手足综合征的维生素预防效果

　　编者按：维生素B6的活化形式之一吡哆醇常被用于预防卡培他滨相关手足综合征，但是吡哆醇预防能否获益的证据尚不充分。

　　2018年6月8日，日本乳腺癌学会《乳腺癌》在线发表名古屋市立大学、爱知癌症中心医院、名古屋医疗中心、藤田保健卫生大学、三重大学、静冈综合医院、岐阜市立医院、京都府立医科大学的研究报告，调查了吡哆醇能否预防晚期或转移性乳腺癌患者卡培他滨所致手足综合征的发生。

　　该多中心随机非盲对照II期研究入组晚期或转移性乳腺癌患者135例，随机分配接受卡培他滨＋吡哆醇（每天60mg，67例）或卡培他滨无吡哆醇（68例），直至发生≥2级手足综合征或疾病进展。主要终点为从研究方案治疗开始至发生≥2级手足综合征的时间。

　　结果，卡培他滨＋吡哆醇、卡培他滨无吡哆醇的≥2级手足综合征发生率分别为28.8%、31.3%，中位时间分别为13.6、10.6个月（风险比：0.75，80%置信区间：0.50～1.13，单侧检验，P=0.18）。

　　因此，该研究结果表明，吡哆醇预防卡培他滨相关手足综合征发作的统计学意义不大。当然，该研究非盲、非安慰剂对照、样本量不大，维生素B6每片10mg每瓶100片正规药房零售价格人民币才几块钱，即使效果不大，损失也不大，副作用也不大。

Breast Cancer. 2018 Jun 8. [Epub ahead of print]

A randomized phase II study evaluating pyridoxine for the prevention of hand-foot syndrome associated with capecitabine therapy for advanced or metastatic breast cancer.

Tatsuya Toyama, Akiyo Yoshimura, Takako Hayashi, Naomi Kobayashi, Kanako Saito, Michiko Tsuneizumi, Masataka Sawaki, Masaya Hattori, Takumi Nakada, Isao Yokota, Hiroji Iwata.

Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; Aichi Cancer Center Hospital, Nagoya, Japan; Nagoya Medical Center, Nagoya, Japan; Fujita Health University, Toyoake, Japan; Mie University, Tsu, Japan; Shizuoka General Hospital, Shizuoka, Japan; Gifu Municipal Hospital, Gifu, Japan; Kyoto Prefectural University of Medicine, Kyoto, Japan.

BACKGROUND: Pyridoxine, an activated form of vitamin B6 used to treat allergic dermatitis, may prevent capecitabine-associated hand-foot syndrome (HFS), although evidence of the benefit of prophylactic pyridoxine is lacking. The aim of this open-label, multicenter, randomized phase II study was to determine whether prophylactic pyridoxine could delay the onset of capecitabine-induced HFS in patients with advanced or metastatic breast cancer.

METHODS: Patients received either concomitant pyridoxine (60 mg per day; pyridoxine group), or no pyridoxine but treatment with capecitabine-containing regimens (no pyridoxine group). Study treatment was administered until the development of grade 2 or worse HFS or disease progression. The primary endpoint was the time to onset of grade 2 or worse HFS from the start of protocol treatment.

RESULTS: A total of 135 patients were randomized to the pyridoxine (n=67) or no pyridoxine (n=68) groups. Grade 2 or worse HFS developed in 19 of 66 patients (28.8%) versus 21 of 67 patients (31.3%) in the pyridoxine and no pyridoxine groups, respectively. The median time to onset of grade 2 or worse HFS was 13.6 and 10.6 months in the pyridoxine and no pyridoxine groups, respectively [hazard ratio=0.75 (80% confidence interval 0.50-1.13), one-sided P=0.18].

CONCLUSIONS: Prophylactic pyridoxine was not shown to have an effect on the onset of capecitabine-associated HFS in this study.

KEYWORDS: Breast cancer; Pyridoxine; Hand-foot syndrome; Capecitabine

DOI: 10.1007/s12282-018-0879-z