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Updated: Feb 15, 2026
Y-90 Radioembolization and PD-1 Inhibitor as Neoadjuvant Treatment in Hepatocellular Carcinoma
Published on: May 24, 2024
Multicenter, randomized, controlled trial of S-1 monotherapy versus S-1 and interferon-α combination therapy for
Hiroaki Nagano1,2, Shuntaro Obi3, Etsuro Hatano4
1Department of Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.
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.
Insights
Combination therapy of S-1 and interferon-alfa (IFN-α) did not significantly improve outcomes for hepatocellular carcinoma (HCC) with extrahepatic metastases compared to S-1 alone. Both treatments showed favorable results, but adding IFN-α increased adverse events.
Area of Science:
- Oncology
- Hepatology
- Medical Oncology
Background:
- Hepatocellular carcinoma (HCC) with extrahepatic metastases lacks effective therapies.
- Combination therapy of S-1 and interferon-alfa (IFN-α) has shown potential antitumor effects.
Purpose of the Study:
- To investigate the clinical efficacy of S-1 monotherapy versus S-1/IFN-α combination therapy for HCC patients with extrahepatic metastases.
- To compare clinical efficacy and adverse events between the two treatment arms.
Main Methods:
- A randomized, open-label, multicenter trial involving 103 patients with HCC and extrahepatic metastases.
- Patients were assigned to either S-1/IFN-α combination therapy or S-1 monotherapy.
- Clinical efficacy and adverse events were assessed and compared between groups.
Main Results:
- The response rate was 22.4% for S-1/IFN-α and 13.7% for S-1, with no significant difference.
- Overall survival and progression-free survival were not significantly different between the groups.
- Grade ≥3 adverse events were more frequent in the S-1/IFN-α group (62.7%) compared to the S-1 group (43.1%).
Conclusions:
- Adding IFN-α to S-1 did not provide a significant beneficial effect for treating HCC with extrahepatic metastases.
- Both treatment regimens demonstrated favorable oncological outcomes compared to previous reports.
- The S-1/IFN-α combination therapy showed a trend towards higher incidence of severe adverse events.
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