Multicenter, randomized, controlled trial of S‐1 monotherapy versus S‐1 and interferon‐α combination therapy for hepatocellular carcinoma with extrahepatic metastases

Aim No effective therapies for extrahepatic metastases from hepatocellular carcinoma (HCC) have yet been identified. Previous studies suggested a potentially promising antitumor effect of combination therapy of S‐1, a novel oral dihydropyrimidine dehydrogenase inhibitor, and interferon (IFN)‐α. The present study aimed to investigate the clinical efficacy of single agent S‐1 and S‐1/IFN‐α for HCC patients with extrahepatic metastases in a randomized, open‐label, multicenter trial. Methods A total of 103 patients with HCC with extrahepatic metastases were randomly assigned to the S‐1/IFN‐α group, receiving the combination of S‐1 and IFN‐α, or the S‐1 group, receiving the single agent of S‐1. Clinical efficacy and adverse events were compared between the two groups. Results A total of 49 patients in the S‐1/IFN‐α group and 51 patients in the S‐1 group were included in the efficacy analysis. The response rate was 22.4% (11/49) in the S‐1/IFN‐α group and 13.7% (7/51) in the S‐1 group; there was no significant difference. Overall and progression‐free survival in the two groups were also not significantly different (1‐year overall survival 50.8% vs. 72.4%, median progression‐free survival 127 days vs. 157 days). The incidence of grade ≥3 adverse events in the S‐1/IFN‐α group was 62.7% (32/51), which tended to be higher than in the S‐1 group (43.1% [22/51]). Conclusions Oncological outcomes in both treatment groups were favorable compared with previous reports, though there was no significant beneficial effect of adding IFN‐α to S‐1 for the treatment of HCC patients with extrahepatic metastases.