Phase II Study of Gemcitabine and Oxaliplatin in Combination With Bevacizumab in Patients With Advanced Hepatocellular Carcinoma

Abstract

A B S T R A C T PurposeHepatocellular carcinoma (HCC) is a vascular tumor with poor prognosis. Given the reported activity of gemcitabine and oxaliplatin (GEMOX) in HCC and the potential benefits of targeting the vascular endothelial growth factor pathway with bevacizumab (B), a phase II study of GEMOX-B was undertaken to define efficacy and toxicity profiles in HCC patients. Patients and MethodsEligible patients had pathologically proven measurable unresectable or metastatic HCC. For cycle 1 (14 days), bevacizumab 10 mg/kg was administered alone intravenously on day 1. For cycle 2 and beyond (28 days/cycle), bevacizumab 10 mg/kg was administered on days 1 and 15, gemcitabine 1,000 mg/m 2 was administered as a dose rate infusion at 10 mg/m 2 /min followed by oxaliplatin at 85 mg/m 2 on days 2 and 16. ResultsThirty-three patients were enrolled and 30 patients were assessable for efficacy. The objective response rate was 20%, and 27% of patients had stable disease. Median overall survival was 9.6 months (95% CI, 8.0 months to not available) and median progression-free survival (PFS) was 5.3 months (95% CI, 3.7 to 8.7 months); the PFS rate at 3 and 6 months was 70% (95% CI, 54% to 85%) and 48% (95% CI, 31% to 65%), respectively. The most common treatment-related grade 3 to 4 toxicities included leukopenia/neutropenia, transient elevation of aminotransferases, hypertension, and fatigue. ConclusionGEMOX-B could be safely administered with close monitoring and had moderate antitumor activity for patients with advanced HCC. The high 6-month PFS rate is encouraging, and this regimen is worthy of further investigation.

Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma

“…These results should be interpreted with caution because a sorafenib-alone arm was not included and high incidence of adverse events related to doxorubicin was noted. Many small-scale trials of combining MTT with cytotoxic chemotherapy have been reported [385][386][387][388][389]. However, the treatment efficacy in terms of tumor response rate and patient survival were similar to those reported for the cytotoxic regimens alone (Table 3) [372,[375][376][377][378][379][380][381][382].…”

Impact of serum vascular endothelial growth factor on prognosis in patients with unresectable hepatocellular carcinoma after transarterial chemoembolization

“…An anti-VEGF monoclonal antibody has been approved for treatment of cancer patients [38] . Promising results that use the anti-VEGF antibody in combination with systemic chemotherapy in treating advanced HCC have recently been reported [39] . Furthermore, several VEGF receptor antagonists currently in clinical trials have been shown to inhibit growth and metastasis of HCC in preclinical studies [24] .…”

“…Poor liver function was commonly identified as an adverse prognostic factor in previous studies [34][35][36][37][38][39] . However, as shown in this study, tumor progression including vascular invasion, extrahepatic metastasis and advanced BCLC stage rather than liver failure was the main adverse prognostic factor after TACE.…”

Molecular therapy for the treatment of hepatocellular carcinoma

“…Combination treatment of bevacizumab with EGFR targeting agents was shown to be safe and revealed promising initial results with a median time to progression of 9 months (Thomas et al, 2007b) (see Table 1). Overall, bevacizumab has shown promising results as a single agent as well as in combination with other targeted therapies and cytotoxic therapy (Zhu et al, 2006) supporting the idea of a vascular targeting therapy for the treatment of HCC.…”