All-Trans-Retinoic Acid Plus Oxaliplatin/Fluorouracil/Leucovorin for Advanced Hepatocellular Carcinoma with Pulmonary Metastasis: A Multicenter Retrospective Study

AIM: To study the impact of All-trans-retinoic acid (ATRA) plus FOLFOX4 compared to FOLFOX4 alone in patients with advanced hepatocellular carcinoma (HCC) with pulmonary metastasis. METHODS: The data of patients with advanced HCC who underwent systemic chemotherapy using FOLFOX4 or ATRA plus FOLFOX4 at the Eastern Hepatobiliary Surgery Hospital, First Hospital of Jilin University, Zhejiang Sian International Hospital and Fujian Cancer Hospital were retrospectively analyzed. The survival outcomes in the 2 groups were compared. RESULTS: From May 2014 to July 2020, 66 patients were suitable to enter into this study. The median survival (14.0 vs 8.0 months, p=0.012), and the median time to progression in the ATRA plus FOLFOX4 group were both significantly longer than those in the FOLFOX4 group (8.7 vs 3.2 months, p=0.002). The 6 month-, 1 year- and 2 year- overall survival rates were also significantly better in the ATRA plus FOLFOX4 group (100.0%, 64.7% and 20.5%; respectively) than the FOLFOX4 group (59.4%, 21.9%, and 12.5%, respectively; p<0.001). Leukocytopenia, fatigue, anorexia, nausea, were the most common acute toxicities, but these were mostly NCI CTCAE Grade 1 or 2. There was no significant difference in adverse events between the two groups. CONCLUSION: ATRA plus FOLFOX4 significantly improved the survival outcomes in patients with advanced HCC with pulmonary metastasis.