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

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-gamma-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.