2017年ASCO會議摘要中，大阪綜合醫院發表了關於維生素K與索拉非尼聯合治療對肝細胞癌的療效和安全性：開放標簽，隨機II期研究。

之前一些動物研究表明，維生素K可增強索拉非尼對肝細胞癌(HCC)的抗癌作用。 我們以前的研究表明，這可能是因為維生素K抑製腫瘤細胞在缺血狀態下des-γ-羧基凝血酶原(DCP)的產生，這種缺血狀態由索拉非尼引起的。DCP被稱為腫瘤生長因子和腫瘤血管生成因子。 為了闡明維生素K在索拉非尼治療中的療效和安全性，我們進行了一個單中心，開放標簽，隨機二期研究。

研究了四十四名晚期HCC患者。根據大血管浸潤和/或肝外擴散分類，他們以1：1的比例隨機分配，以接受維生素K +索拉非尼或單獨接受索拉非尼。抗癌效果通過改良RECIST進行評估。

兩組基線特征(性別，年齡，Child-Pugh狀態和背景性肝病)無顯著差異。 維生素K +索拉非尼組與無索拉非尼組相比，無進展生存期(PFS)顯著延長(中位時間3.7個月vs 1.5個月，P = 0.001，風險比0.35)。維生素K +索拉非尼組和索拉非尼組單獨組的疾病控製率分別為55%18%(P = 0.012)。 另一方麵，維生素K +索拉非尼組的中位總生存期(OS)為12個月，索拉非尼組為11.5個月(P = 0.27，危險比為0.67)。然而，在維生素K +索拉非尼組中，22例患者中有5例(23%)存活了21個月以上，索拉非尼單獨組中有1例(5%)死亡。兩組間不良事件發生率無明顯差異。

研究結果表明，維生素K可以安全地改善索拉非尼治療晚期HCC的抗癌療效。

Abstract:

Background: Some animal studies showed that vitamin K enhances anti-cancer action of sorafenib for hepatocellular carcinoma (HCC). Our previous examination suggested that it might be because the vitamin K suppresses des-γ-carboxy prothrombin (DCP) production of tumor cells under ischemic status caused by sorafenib. The DCP is known as a tumor growth factor and a tumor angiogenesis factor. In order to clarify the efficacy and safety of vitamin K dosing in sorafenib treatment, we have performed a single center, open label, randomized, phase 2 study. Methods: Forty-four patients with advanced HCC were studied. They were randomly assigned in a 1:1 ratio, to receive vitamin K + sorafenib or to receive sorafenib alone, stratified according to macrovascular invasion and/or extrahepatic spread. The anti-cancer outcome was evaluated by modified RECIST. Results: There was no significant difference between the two groups in baseline characteristics (gender, age, Child-Pugh status and background liver disease). The progression-free survival (PFS) was significantly prolonged in the vitamin K + sorafenib group compared with sorafenib alone group (median time 3.7 months vs. 1.5 months, P = 0.001, hazard ratio 0.35). The disease control rates were 55% in vitamin K + sorafenib group and 18% in sorafenib alone group (P = 0.012). On the other hand, median overall survival (OS) times were 12 months in vitamin K + sorafenib group and 11.5 months in sorafenib alone group (P = 0.27, hazard ratio 0.67). However, 5 patients (23%) of 22 survived for more than 21 months in the vitamin K + sorafenib group, while one (5%) of 22 did in sorafenib alone group. There was no significant difference in incidence of adverse events between the two groups. Conclusions: The vitamin K dosing safely improved anti-cancer outcome of sorafenib treatment against advanced HCC.