Hiroaki Nagano1,2, Shuntaro Obi3, Etsuro Hatano4, Shuichi Kaneko5, Fumihiko Kanai6, Masao Omata6, Akihito Tsuji7, Toshiyuki Itamoto8, Kazuhide Yamamoto9, Masatoshi Tanaka10, Shoji Kubo11, Koichi Hirata12, Hideji Nakamura13, Yoshito Tomimaru1, Takeharu Yamanaka14, Shinsuke Kojima15, Morito Monden1. 1. Department of Surgery, Graduate School of Medicine, Osaka University, Suita, Japan. 2. Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan. 3. Department of Gastroenterology and Hepatology, Kyoundo Hospital of the Sasaki Institute, Tokyo, Japan. 4. Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. 5. Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan. 6. Department of Gastroenterology, University of Tokyo, Tokyo, Japan. 7. Department of Clinical Oncology, Kochi Health Science Center, Kochi, Japan. 8. Department of Surgery, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. 9. Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. 10. Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan. 11. Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan. 12. Department of Surgery, Surgical Oncology & Science, Sapporo Medical University, Sapporo, Japan. 13. Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan. 14. Department of Biostatistics, Yokohama City University School of Medicine, Yokohama, Japan. 15. Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, Kobe, Japan.
Abstract
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.
RCT Entities:
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.