Phase II Trial of Sorafenib in Combination with Capecitabine in Patients with Hepatocellular Carcinoma: INST 08‐20

LESSONS LEARNED. There continues to be a lack of systemic options for advanced hepatocellular carcinoma (HCC); sorafenib and, very recently, regorafenib are the only approved options. There exists a potential to combine sorafenib with chemotherapeutic agents shown to be active in HCC, such as capecitabine, safely. Good tumor response was observed, with objective improvement in a few patients seldom seen by single agent sorafenib; however, because of the limited number of patients, meaningful conclusions on survival cannot be drawn. BACKGROUND. Sorafenib is the currently approved first‐line treatment for hepatocellular carcinoma (HCC). Capecitabine has antitumor activity in hepatobiliary cancers. The combination of the two, if tolerated, could possibly improve antitumor response, and survival. METHODS. Patients with advanced HCC ineligible for locoregional therapy, Eastern Cooperative Oncology Group performance status of ≤2, Child‐Pugh class A or B‐7 cirrhosis, hemoglobin ≥8.5 g/dL, platelets ≥50,000/μL, absolute neutrophil count (ANC) ≥1,500 cells/μL, and serum creatinine of ≤2.0 mg/dL were recruited. All subjects received a combination of sorafenib and capecitabine, on a 14‐day 7‐days on 7‐days off schedule. The primary end point was safety and secondary end points were overall survival (OS) and disease control rate. RESULTS. A total of 15 out of 47 patients met inclusion criteria. Median age was 64 years (56–79) and 77% were male. With a median follow‐up of 12 months, median OS was 12.7 months (95% confidence interval [CI], 8.5–23.4). Disease control rate was 77% (complete response 8%, partial response 8%, and stable disease 61%). Common adverse events were as follows: (a) thrombocytopenia (64%); (b) anemia (14%); (c) hypophosphatemia (21%); (d) hypomagnesemia (14%); (e) hyperbilirubinemia (21%); (f) increased aspartate transaminase (AST) (14%); (g) hand‐foot syndrome (21%); and (h) deep vein thrombosis (21%). CONCLUSION. At tolerable doses, the combination of sorafenib and capecitabine seems an active and safe palliative treatment for HCC in class A and B‐7 patients with cirrhosis. The small sample size does not allow comparison with single‐agent sorafenib.