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

Andrew X. Zhu, Lawrence S. Blaszkowsky, David P. Ryan, Jeffrey W. Clark, Alona Muzikansky, Kerry Horgan, Susan Sheehan, Kelly E. Hale, Peter C. Enzinger, Pankaj Bhargava, Keith Stuart

From the Massachusetts General Hospital; Dana-Farber Cancer Institute; and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.

Address reprint requests to Andrew X. Zhu, MD, PhD, Tucker Gosnell Center for Gastrointestinal Cancers, Massachusetts General Hospital Cancer Center, 100 Blossom St, Cox 640, Boston, MA 02114; e-mail: azhu{at}partners.org

PURPOSE: Hepatocellular 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 METHODS: Eligible 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/m² was administered as a dose rate infusion at 10 mg/m²/min followed by oxaliplatin at 85 mg/m² on days 2 and 16.

RESULTS: Thirty-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.

CONCLUSION: GEMOX-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.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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