Impact of vitamin K dosing during sorafenib treatment for hepatocellular carcinoma: Effect on ischemic tumor cell damage caused by sorafenib.

e15585 Background: Sorafenib’s anticancer effects are limiting. It was reported that combination of vitamin K and sorafenib inhibited HCC growth in vitro and in vivo study. We examined retrospectively the impact of vitamin K dosing during sorafenib treatment. Methods: Sixty-four patients (the Barcelona Clinic Liver Cancer (BCLC) stage B/C 24/40) were studied. Twenty-eight out of them were orally given vitamin K2 (45mg daily) during sorafenib treatment. There were no relevant differences between the vitamin K dosing and sorafenib alone groups in characteristics at baseline. The radiologic assessment was performed according to modified RECIST. Results: Median PFS was 7.0 months vs. 2.0 months in vitamin K dosing group and sorafenib alone one (P < 0.001), respectively. Vitamin K dosing also prolonged OS significantly (median survival: 12.5 months vs. 10.0 months, P = 0.016). Subgroup analysis revealed that vitamin K dosing prolonged OS especially in patients without vascular invasion or extrahepatic spread. In such patients, median OS was 29.0 months in vitamin K dosing group, whereas that of sorafenib alone group was 15.5 months (P = 0.014). On the other hand, a unique difference in DCP changes (pre vs. 8 weeks after) were observed in patients with partial response or stable disease. Serum DCP levels was increased in sorafenib alone group despite suppressed tumor growth (2.28±0.91 → 2.64±1.03 Log mAU/mL, P = 0.048). In contrast, vitamin K dosing group showed decreased DCP levels (2.01±0.58→1.30±0.29 Log mAU/mL, P = 0.003). Discussion and Conclusions: DCP is an indicator reflecting vitamin K deficiency and ischemic status of HCC tumor cells. DCP elevation seen in the sorafenib alone group shows ischemic status of tumor cells resulting from impaired angiogenesis. The DCP elevation could jeopardize sorafenib’s antitumor action, because DCP is reported to work as a growth factor for HCC and vessel endothelial cells. Large amount of vitamin K dosing suppresses DCP production by increasing vitamin K concentration inside tumor cells. The nontoxic agent, vitamin K, dosing could augment antitumor action of sorafenib possibly by enhancing ischemic damage of tumor cells.