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.
['Nagano|Hiroaki|H|', 'Obi|Shuntaro|S|', 'Hatano|Etsuro|E|', 'Kaneko|Shuichi|S|', 'Kanai|Fumihiko|F|', 'Omata|Masao|M|', 'Tsuji|Akihito|A|', 'Itamoto|Toshiyuki|T|', 'Yamamoto|Kazuhide|K|', 'Tanaka|Masatoshi|M|', 'Kubo|Shoji|S|', 'Hirata|Koichi|K|', 'Nakamura|Hideji|H|', 'Tomimaru|Yoshito|Y|', 'Yamanaka|Takeharu|T|', 'Kojima|Shinsuke|S|', 'Monden|Morito|M|']
S-1 hepatocellular carcinoma interferon randomized controlled trial