J Cancer 2017; 8(11):1988-1994. doi:10.7150/jca.18900

Research Paper

Clinical Impact of Vitamin K Dosing on Sorafenib Treatment for Hepatocellular Carcinoma

Yoshimichi Haruna1✉, Noriko Hasegawa1, Kazuho Imanaka1, Seiichi Kawamoto2, Atsuo Inoue1

1. Department of Gastroenterology and Hepatology, Osaka General Medical Center, Osaka, Japan
2. Department of Diagnostic Imaging, Osaka General Medical Center, Osaka, Japan

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Haruna Y, Hasegawa N, Imanaka K, Kawamoto S, Inoue A. Clinical Impact of Vitamin K Dosing on Sorafenib Treatment for Hepatocellular Carcinoma. J Cancer 2017; 8(11):1988-1994. doi:10.7150/jca.18900. Available from http://www.jcancer.org/v08p1988.htm

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Background: Some researchers have suggested that vitamin K enhances the antitumor effect of sorafenib for hepatocellular carcinoma (HCC) in vitro and in vivo. In this study, we examined the clinical impact of vitamin K dosing for sorafenib treatment.

Methods: Twenty-nine out of 65 patients treated with sorafenib for HCC were simultaneously dosed with vitamin K. We retrospectively investigated progression-free survival (PFS) and overall survival (OS) in the vitamin K-dosed group and sorafenib alone group. We also examined the changes in serum des-γ-carboxy prothrombin (DCP) levels, which vitamin K is involved with.

Results: The median PFS was prolonged in the sorafenib + vitamin K group compared with the sorafenib alone group (6.0 months and 2.0 months, respectively; P<0.001, hazard ratio〔HR〕: 0.25). The median OS was also significantly extended (12.5 months vs. 10.0 months; P=0.009, HR: 0.47). Despite suppressed tumor growth, serum DCP levels had increased in cases of disease-controlled patients in the sorafenib alone group 8 weeks after the beginning of treatment, (2.28±0.91 to 2.64±1.03, P= 0.048). In contrast, the serum DCP levels of the sorafenib + vitamin K group had declined both in patients with controlled disease and in patients with progressive disease (1.97±0.57 to 1.29±0.28, P=0.002 and 2.90±1.32 to 1.78±0.53, P=0.034, respectively).

Conclusions: To the best of our knowledge, this is the first clinical report showing enhanced antitumor action of sorafenib by vitamin K. Our clinical findings suggest that vitamin K may have the synergistic effect by suppressing production of DCP, a tumor growth and angiogenesis factor.

Keywords: hepatocellular carcinoma, vitamin K, sorafenib, des-γ-carboxy prothrombin, tumor ischemia