Chemoembolization in patients with hepatocellular carcinoma

Transcatheter arterial chemoembolization (TACE) is the standard of care for nonsurgical patients with preserved liver function with large or multinodular noninvasive hepatocellular carcinoma (HCC) confined to the liver. The administration of an anticancer-in-oil emulsion followed by embolic agents is the most popular TACE technique; however, the introduction of embolic, drug-eluting beads (DEB) has provided an alternative to conventional regimens. Experimental studies have shown that DEB-TACE results in a safe pharmacokinetic profile and effective tumor killing in animal models. Clinical experiences have confirmed that DEB-TACE provides a combined ischemic and cytotoxic effect locally, with significantly reduced drug-related toxicity and liver toxicity compared with conventional TACE. The addition of molecular targeted drugs to the therapeutic armamentarium for HCC has prompted the design of clinical trials aimed at investigating the synergies between TACE and systemic treatments. Combining TACE with antiangiogenic agents represents a promising strategy because TACE is thought to cause local hypoxia, resulting in a temporary increase in levels of vascular endothelial growth factor. Recently, a large phase 2, randomized, double-blind, placebo-controlled trial (the SPACE study) indicated that the concurrent administration of DEB-TACE and sorafenib has a manageable safety profile and suggested that the time to progression (TTP) and time to vascular invasion or extrahepatic spread may be improved compared with DEB-TACE alone. These data support the further evaluation of molecular targeted, systemically active agents in combination with DEB-TACE in a phase 3 setting.