Phase ii trial of sorafenib in combination with capecitabine in patients with hepatocellular Carcinoma: INST 08-20

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.