A randomized phase II study evaluating pyridoxine for the prevention of hand–foot syndrome associated with capecitabine therapy for advanced or metastatic breast cancer
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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.
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.
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].
Prophylactic pyridoxine was not shown to have an effect on the onset of capecitabine-associated HFS in this study.
KeywordsBreast cancer Pyridoxine Hand–foot syndrome Capecitabine
This study was conducted by the Tokai Breast Cancer Research Group (TBCRG), of which HI is a director and TT an organized committee member. The TBCRG received no research funding from any pharmaceutical companies. However, research funding was provided to the data management center, the Japan Clinical Research Support Unit, by Chugai Pharmaceutical Co., Ltd., under the study contract. Chugai Pharmaceutical Co., Ltd. took no part in this study other than providing information relevant to the proper use of the study drug. We greatly appreciate the patients who participated in this trial. We also thank the investigators and their collaborators. We thank Clare Cox, Ph.D., from Edanz Group (http://www.edanzediting.com/ac) for editing a draft of this manuscript. Finally, we thank Yumiko Nomura for conscientious data management.
Compliance with ethical standards
Conflict of interest
TT received a research grant from AstraZeneca, and Chugai Pharmaceutical Co., Ltd. HI received an honorarium from Chugai Pharmaceutical Co., Ltd., and AstraZeneca, and research funding for the development of new drugs from MSD K.K., AstraZeneca, Kyowa Hakko Kirin Co., Ltd., GSK, Daiichi-Sankyo Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Novartis Pharma K.K., Bayer Yakuhin Ltd., and Pfizer Japan Inc. No other authors have conflicts of interest to declare.