Pilot study of combination chemotherapy of S-1, a novel oral DPD inhibitor, and interferon-α for advanced hepatocellular carcinoma with extrahepatic metastasis

BACKGROUND. To the authors' knowledge, there is no effective therapy for extrahepatic metastasis of hepatocellular carcinoma (HCC). In a pilot study, the results of combination therapy of S-1, a novel oral dehydropyrimidine dehydrogenase (DPD) inhibitor, and interferon-alpha (IFN-alpha) are reported for HCC patients with extrahepatic metastasis. METHODS. Twelve patients with extrahepatic metastasis of HCC were enrolled in the pilot study. S-1 was administered orally at a dose based on body surface area, twice daily after a meal, for 4 weeks. IFN-alpha was injected subcutaneously on Days 1, 3, and 5 of each week. One course consisted of consecutive administration for 28 days followed by 14 days rest. RESULTS. An objective response was observed in 3 (25%) of 12 patients. The overall 1-year survival rate was 61.7%. Grade 3 leukocytopenia was observed in 1 patient (8.3%). No severe toxicity or treatment- related deaths were observed. CONCLUSIONS. The combination therapy of S-1 and IFN-alpha appears to be highly efficacious, with low toxicity in patients with extrahepatic metastases of HCC. The combination chemotherapy of oral S-1 and subcutaneous IFN-alpha is a potentially promising treatment strategy for advanced HCC with extrahepatic metastasis.