2017年ASCO会议摘要中，大阪综合医院发表了关于维生素K与索拉非尼联合治疗对肝细胞癌的疗效和安全性：开放标签，随机II期研究。

之前一些动物研究表明，维生素K可增强索拉非尼对肝细胞癌(HCC)的抗癌作用。 我们以前的研究表明，这可能是因为维生素K抑制肿瘤细胞在缺血状态下des-γ-羧基凝血酶原(DCP)的产生，这种缺血状态由索拉非尼引起的。DCP被称为肿瘤生长因子和肿瘤血管生成因子。 为了阐明维生素K在索拉非尼治疗中的疗效和安全性，我们进行了一个单中心，开放标签，随机二期研究。

研究了四十四名晚期HCC患者。根据大血管浸润和/或肝外扩散分类，他们以1：1的比例随机分配，以接受维生素K +索拉非尼或单独接受索拉非尼。抗癌效果通过改良RECIST进行评估。

两组基线特征(性别，年龄，Child-Pugh状态和背景性肝病)无显着差异。 维生素K +索拉非尼组与无索拉非尼组相比，无进展生存期(PFS)显着延长(中位时间3.7个月vs 1.5个月，P = 0.001，风险比0.35)。维生素K +索拉非尼组和索拉非尼组单独组的疾病控制率分别为55%18%(P = 0.012)。 另一方面，维生素K +索拉非尼组的中位总生存期(OS)为12个月，索拉非尼组为11.5个月(P = 0.27，危险比为0.67)。然而，在维生素K +索拉非尼组中，22例患者中有5例(23%)存活了21个月以上，索拉非尼单独组中有1例(5%)死亡。两组间不良事件发生率无明显差异。

研究结果表明，维生素K可以安全地改善索拉非尼治疗晚期HCC的抗癌疗效。

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.