Abstract
BACKGROUND: We have previously reported that vitamin K dosing augments the anticancer effects of sorafenib by suppressing levels of des-γ-carboxy prothrombin, a known tumor growth and angiogenesis factor produced in HCC under sorafenib-induced ischemia. Herein, we aimed to establish whether vitamin K dosing could afford a similar anticancer effect when combined with transarterial chemoembolization (TACE). METHODS: We performed a randomized controlled trial, assigning patients with unresectable HCC (1:1) to TACE + vitamin K or TACE alone groups. Co-primary endpoints were objective response rate and PFS; the secondary endpoint was safety. RESULTS: The TACE + vitamin K group (n = 50) exhibited a significantly higher objective response rate than the TACE alone group (n = 51) (96.0% vs. 82.4%, p = 0.028). The PFS was significantly longer in the TACE + vitamin K group than that in the TACE alone group (median time: 262 days [95% confidence interval (CI), 35.8-488.2 days] vs. 146 days [95% CI, 111.6-180.4 days]; p = 0.013, hazard ratio: 0.55 [95% CI, 0.34-0.89]). There were no significant differences in the incidence of adverse events between groups. CONCLUSIONS: Compared with TACE alone, vitamin K dosing combined with TACE improved anticancer outcomes. CLINICAL TRIAL NUMBER: UMIN000026404.