Combination of capecitabine, oxaliplatin with bevacizumab in treatment of advanced hepatocellular carcinoma (HCC): A phase II study

Abstract

4574 Background: Hepatocellular carcinoma (HCC) is one of the most common cancers globally and its incidence of in USA is increasing. Unfortunately, most patients with HCC are unsuitable for surgical resection or transplantation. Because of the heterogeneity of this disease and poor liver function in many patients, there is no generally accepted standard chemotherapy regimen for HCC. Efforts have been made to investigate effective and tolerable therapy for patients with advanced HCC. We conducted a phase II study to evaluate the efficacy and feasibility of the combination of bevacizumab, oxaliplatin and capecitabine in patients with advanced or metastatic HCC. The primary goal of the study was to evaluate the progression-free survival rate. The secondary endpoints include response, overall survival and toxicity. Methods: Patients with advanced or unresectable untransplantable metastatic HCC who had adequate bone marrow, liver and renal function (ANC ≥ 1,500/mm3, platelets ≥ 75,000/mm3, serum creatinine ≤ 2.0 mg/dl, total bilirubin ≤ 3.0 mg/dl, transaminases ≤ 5 upper limit of normal, and INR ≤ 1.5) were eligible to the study. Bevacizumab (5 mg/kg) and oxaliplatin (130 mg/m2) were administered intravenously day 1 of each 21- day cycle. Capecitabine (825 mg/m2, twice a day) was administered days 1 to 14. Results: Thirty patients (male/female ratio of 23/7) have been enrolled, with a median age of 57 (range 23–85). The average number of treatment cycles was 8 (2–25 cycles). Of evaluable patients, 3 patients (11%) achieved partial response, 21 patients had stable disease (78%) with a disease control rate of 89%. The mean PFS was 5.4 months with 3- and 6- months PFS of 70%, and 40%. There were 33% Gr. 2/3 oxaliplatin-related peripheral neuropathy and 11 % capecitabine-related Gr. 2/3 hand- foot syndrome. One patient had gastrointestinal perforation and sepsis after his first administration of bevacizumab and oxaliplatin. Two patients had esophageal varices-related bleeding, likely disease-related. Conclusions: The results demonstrate that the combination of bevacizumab, oxaliplatin and capecitabine is effective and tolerable in treatment of advanced HCC and should be considered for the further investigation. [Table: see text]