Subject terms
HCC, HCC and extrahepatic metastasis
HEPATOCELLULAR CARCINOMA
The majority of hepatocellular carcinoma (HCC) cases are diagnosed at an advanced stage. Currently, there are only a few therapeutic methods available for patients with advanced HCC and extrahepatic metastasis (EHM). Systemic chemotherapy, such as FOLFOX4 (infusions of fluorouracil, leucovorin, and oxaliplatin), has been reported for treating advanced HCC with EHM, but its effectiveness is very poor. In this randomized, double-blind, placebo-controlled study, we aimed to assess the efficacy and safety of FOLFOX4 with all-trans-retinoic acid (ATRA) as a palliative treatment for HCC patients with EHM, compared to FOLFOX4 with a placebo. The primary endpoint was overall survival (OS), and subsequently, an exploratory model was developed based on bioinformatics to predict the efficacy of FOLFOX4-ATRA treatment. A total of 108 patients were randomly assigned in a 1:1 ratio to receive either FOLFOX4-ATRA or FOLFOX4-placebo. The intention-to-treat (ITT) population showed a median OS of 16.2 months for the FOLFOX4-ATRA group, compared with 10.7 months for the FOLFOX4-placebo group (HR 0.56, 95% CI 0.33–0.93; 