Phase II trial of sorafenib with capecitabine and oxaliplatin (SECOX) in patients with locally advanced or metastatic hepatocellular carcinoma

Abstract

Background: This is a single arm, multi-centre, phase II study to assess the efficacy and tolerability of sorafenib combining oxaliplatin and capecitabine for the treatment of advanced hepatocellular carcinoma (HCC) patients. Methods: Advanced HCC patients with no prior systemic therapy received SECOX regime – sorafenib 400 mg bid (Day 1−14), oxaliplatin 85 mg/m2 (Day 1) and capecitabine 1700 mg/m2 (Day 1−7) every two weeks. Response assessment using RECIST criteria was performed after 4 cycles. Patients who achieved partial response or stable disease would receive another 4 cycles till a maximum of 8 cycles. Afterwards, sorafenib was continued till disease progression. The primary endpoint was time-toprogression (TTP) and the secondary endpoints were tumor response rate (RR), overall survival (OS) and tolerability. Results: A total of 51 patients were enrolled in the trial. The median age was 58 years (range, 28−81) and all patients were in ECOG Performance Status 0−1. Eighty-four percent of patients were chronic hepatitis B carriers and 98% of patients had Child A cirrhosis. Ten (20%) patients had tumor vascular invasion and 41 (80%) patients had extra-hepatic metastasis. The best RR was 14 % and another 61% of patients achieved stable disease. Overall, 75% of patients derived clinical benefits from SECOX regime for at least 8 weeks. The median TTP was 7.1 months (1.7–19.9) and OS was 10.2 months (2.1–20.5). Hand-Foot-Skin reaction (73%), diarrhea (69%) and neutropenia (63%) were the most commonly encountered toxicities, with the majority of patients having grade 1 or 2 toxicity. No treatmentrelated death was reported. Conclusion: The SECOX regime demonstrates highly significant clinical activity and good tolerability in advanced HCC patients. Our data support a randomized trial comparing SECOX versus Sorafenib alone for treatment of advanced HCC.