Treatment of advanced hepatocellular carcinoma with emphasis on hepatic arterial infusion chemotherapy and molecular targeted therapy

Abstract

Advanced hepatocellular carcinoma is defined as liver cancer with vascular invasion or extrahepatic metastasis that is untreatable by local therapy. In Japan, hepatic arterial infusion chemotherapy (HAIC) with interferon plus 5-fluorouracil (5-FU) or a combination of low-dose 5-FU and cisplatin, referred to as low-dose FP, is administered for treating advanced liver cancer and yields favorable outcomes. Outside Japan, the molecular targeted agent, sorafenib, is used as a first-line treatment for advanced liver cancer. New drug development for advanced liver cancer and clinical trials on combination therapy with sorafenib and HAIC are currently underway. The prognosis of advanced liver cancer will significantly improve if these clinical trials yield positive results.

Keywords: Advanced liver cancer; HAIC combined with sorafenib; Hepatic arterial infusion chemotherapy; Molecular target therapy; Sorafenib.

Fig. 1

Consensus-based treatment algorithm for HCC proposed by the Japan Society of Hepatology, revised in 2010. HAIC is recommended for treating multiple liver cancer and HCC with vascular invasion. Sorafenib is recommended for patients unresponsive to TACE and for those with liver cancer with vascular invasion or extrahepatic spread. Modified with permission from Kudo et al. [1].

Fig. 2

Treatment modality of initially diagnosed HCC in Japan. Only 5% patients received chemotherapy [19].

Fig. 3

Administration method of chemotherapeutic agent. Nearly 90% patients received HAIC [19].

Fig. 4

Result of HAIC in Japan. The response rate is 45.9% and disease control rate is 76.5% [19].

Fig. 5

Most commonly used HAIC regimens in Japan. IFN + 5-FU regimen followed by low-dose FP therapy is the most popular.

Fig. 6

a Kaplan-Meier analysis of overall survival of 52 patients treated by HAIC with low-dose FP therapy. b Kaplan-Meier analysis of time to progression in 52 patients treated by HAIC with low-dose FP therapy. The median time to progression was 4.1 months (95% CI 2.1–6.1). c The median survival for patients who underwent HAIC with low-dose FP therapy at Kinki University and who responded to the therapy (responders) was 40.7 months, which was significantly longer than nonresponders (6.8 months). Reproduced with permission from Ueshima, et al. [20]

Fig. 7

Survival of patients with HCC with vascular invasion and/or extrahepatic spread and Child-Pugh A/B: transcatheter arterial chemoembolization and HAIC after case matching according to propensity score analysis. Number of patients before case matching in HAIC and BSC was 824 and 1,345, respectively.

Fig. 8

Current development status of molecular targeted agents