Ginkgo biloba extract in combination with sorafenib is clinically safe and tolerable in advanced hepatocellular carcinoma patients

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• 作者：Zhen Cai ; Chunge Wang ; Peiwen Liu ; Peng Shen ; Yingying Han ; Nawen Liu ; ^{nawenliun@sina.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Ginkgo biloba extract ; Sorafenib ; Hepatocellular carcinoma ; Metastasis ; Chemotherapy
• 刊名：Phytomedicine
• 出版年：2016
• 出版时间：15 November 2016
• 年：2016
• 卷：23
• 期：12
• 页码：1295-1300
• 全文大小：547 K

文摘

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.

Study design

Patients with advanced HCC were treated with increasing doses of GBE in combination with sorafenib.

Methods

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 400 mg twice daily (BID) and increasing doses (cohort 1: 60 mg, cohort 2: 120 mg, cohort 3: 240 mg, cohort 4: 360 mg) 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.

Results

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 240 mg QD plus sorafenib 400 mg 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.

Conclusions

The combination of GBE (240 mg QD) and standard dose sorafenib (400 mg BID) is safe and tolerable among patients with advanced HCC. Early signs of antitumor activity may warrant further development of this combination.