Combination Trans Arterial Chemoembolization (TACE) Plus Sorafenib for the Management of Unresectable Hepatocellular Carcinoma: A Systematic Review of the Literature

Hepatocellular carcinoma (HCC) is the most common liver neoplasm and the fifth most common cancer worldwide. Intermediate stage HCC [traditionally defined as Barcelona Clinic Liver Cancer (BCLC) B disease and traditionally treated with trans arterial chemoembolization (TACE)] and advanced stage HCC (traditionally defined as BCLC C disease and traditionally treated with sorafenib) are two distinct disease entities with rapidly evolving multimodality treatment approaches. In this systematic review we explore the evidence surrounding the value of using a TACE/sorafenib combination in these two subsets of HCC. PubMed, Medline, the Cochrane Library, EMBASE and Google Scholar were searched using the terms "HCC" OR "Hepatoma" or "Liver cancer" AND "TACE" OR "Chemoembolization" AND "Sorafenib" and specifying only English literature. Outcomes of interest included time to progression and overall survival (TTP and OS), tumor response, and toxicities. A total of 17 potentially relevant trials were identified, of which six studies were excluded. Hence, 11 trials involving 1,000 patients were included, encompassing two phase 1 studies, one phase 3 study, two retrospective analyses and six phase 2 studies. Median TTP was reported in five out of 11 studies and it ranged from 6.3 to 9.0 months. Median OS was reported in five out of 11 studies and it was similarly variable as PFS, ranging from 12 to 29 months. The DCR (disease control rate) was reported in eight out of 11 studies, ranging from 32 to 95 %. Frequently reported grade 3/4 toxicities were increased aspartate transaminase/alanine transaminase, fatigue, hypertension, hand-foot skin reaction and diarrhea. The sorafenib/TACE combination shows promise as an effective and tolerable treatment strategy for intermediate stage/advanced HCC. The reported efficacy of a sorafenib/TACE combination appears to compare favorably with sorafenib or TACE monotherapies, the most commonly implemented strategies for unresectable HCC. Further clinical studies are warranted to accurately determine which patients are expected to benefit most from such combination strategies.