Abstract

Chemotherapy for hepatocellular carcinoma (HCC) can be categorized as systemic chemotherapy or hepatic arterial infusion chemotherapy (HAIC). Sorafenib is acknowledged as a standard systemic chemotherapeutic agent for advanced HCC on the basis of the results of two pivotal randomized controlled trials which demonstrated its superiority over placebo. Recently, non-inferiority of lenvatinib to sorafenib in the first line and superiority of regorafenib to placebo in the second line have been demonstrated in terms of the overall survival. Furthermore, immuno-oncology agents have been introduced as promising agents for advanced HCC. Thus, various novel systemic agents are currently under development. On the other hand, HAIC is often used in Japan, as it is expected to be associated with a stronger antitumor effect and a lower incidence of systemic adverse reactions as compared to systemic chemotherapy. However, because no randomized controlled trials have yet established the survival advantage of HAIC, no consensus has been reached as to the standard treatment for advanced HCC. To elucidate the usefulness of HAIC, two randomized controlled trials of sorafenib plus HAIC with cisplatin vs. sorafenib alone and of sorafenib plus HAIC with 5-FU + cisplatin vs. sorafenib alone were conducted in Japan. The former phase II trial demonstrated the effectiveness, in terms of prolonging the overall survival, of sorafenib plus HAIC with cisplatin as compared to sorafenib alone in patients with advanced HCC, whereas the latter phase III trial failed to show prolongation of survival in patients receiving sorafenib plus HAIC with 5-FU and cisplatin as compared to those receiving sorafenib alone. The role of HAIC, therefore, remains to be clarified in patients with advanced HCC. Further studies are needed to clarify the best treatment strategy for advanced HCC: use of molecular-targeted agents or HAIC, or both.

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