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

BACKGROUND: 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 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.

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 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.

CONCLUSIONS: 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.