Cai Zhen, Wang Chunge, Liu Peiwen, Shen Peng, Han Yingying, Liu Nawen
Tianjin First Center Hospital, No. 24 Fukang Road, Nankai District, Tianjin 300192, China.
Tianjin First Center Hospital, No. 24 Fukang Road, Nankai District, Tianjin 300192, China.
Phytomedicine. 2016 Nov 15;23(12):1295-1300. doi: 10.1016/j.phymed.2016.07.002. Epub 2016 Jul 9.
Sorafenib is the only therapy shown to improve overall survival in advanced hepatocellular carcinoma (HCC). However, the clinical efficacy of sorafenib is limited. Combination therapy targeting multiple signaling pathways may improve outcomes. Ginkgo biloba extract (GBE) has exhibited antitumor activity in multiple human cancers.
HYPOTHESIS/PURPOSE: This study was designed to evaluate the tolerability and effectiveness of GBE combined with sorafenib in patients with advanced HCC.
Patients with advanced HCC were treated with increasing doses of GBE in combination with sorafenib.
We first determined the maximum tolerated dose (MTD) of GBE, then the patients were treated with GBE at the MTD to evaluate its safety and efficacy. 27 patients were enrolled in the first part of our study and treated with sorafenib 400mg twice daily (BID) and increasing doses (cohort 1: 60mg, cohort 2: 120mg, cohort 3: 240mg, cohort 4: 360mg) of GBE once daily (QD). An additional group of 32 new patients next to the 27 described before were accrued for the second part of our study, and all these 32 patients were eligible for the evaluation of toxicity and efficacy.
No patient in cohort 1 and 2 experienced a dose-limiting toxicity (DLT). One of the ten patients in cohort 3 experienced a DLT. DLT occurred in two of the three initial patients in cohort 4. Cohort 3 (GBE 240mg QD plus sorafenib 400mg BID) was considered to be the MTD. Three patients had a partial response, 21 had stable disease, and 8 had progressive disease. The median times to progression and overall survival were 2.5 and 11.6 months, respectively. Compared with previous study, the toxicities of the combination therapy were similar with those observed in sorafenib monotherapy, GBE in combination with sorafenib slightly improved OS.
The combination of GBE (240mg QD) and standard dose sorafenib (400mg BID) is safe and tolerable among patients with advanced HCC. Early signs of antitumor activity may warrant further development of this combination.
索拉非尼是唯一被证实可提高晚期肝细胞癌（HCC）总生存率的治疗药物。然而，索拉非尼的临床疗效有限。针对多条信号通路的联合治疗可能改善治疗效果。银杏叶提取物（GBE）在多种人类癌症中已显示出抗肿瘤活性。
假设/目的：本研究旨在评估GBE联合索拉非尼治疗晚期HCC患者的耐受性和有效性。
晚期HCC患者接受递增剂量的GBE联合索拉非尼治疗。
我们首先确定GBE的最大耐受剂量（MTD），然后让患者接受MTD剂量的GBE治疗以评估其安全性和有效性。我们研究的第一部分纳入了27例患者，接受索拉非尼每日两次、每次400mg（BID），以及递增剂量（第1组：60mg，第2组：120mg，第3组：240mg，第4组：360mg）的GBE每日一次（QD）治疗。在上述27例患者之外，又纳入了32例新患者用于我们研究的第二部分，这32例患者均符合毒性和疗效评估标准。
第1组和第2组中没有患者出现剂量限制性毒性（DLT）。第3组的10例患者中有1例出现DLT。第4组最初的3例患者中有2例出现DLT。第3组（GBE 240mg QD加索拉非尼400mg BID）被认为是MTD。3例患者出现部分缓解，2例病情稳定，8例病情进展。中位进展时间和总生存期分别为2.5个月和11.6个月。与之前的研究相比，联合治疗的毒性与索拉非尼单药治疗中观察到的毒性相似，GBE联合索拉非尼可略微改善总生存期（OS）。
GBE（240mg QD）与标准剂量索拉非尼（400mg BID）联合应用于晚期HCC患者是安全且可耐受的。抗肿瘤活性的早期迹象可能支持进一步研发这种联合治疗方案。
