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

Cancer. 2008 Apr 15;112(8):1765-71. doi: 10.1002/cncr.23356.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Antimetabolites, Antineoplastic / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / secondary
  • Dihydrouracil Dehydrogenase (NADP) / antagonists & inhibitors*
  • Drug Combinations
  • Female
  • Follow-Up Studies
  • Humans
  • Immunologic Factors / administration & dosage*
  • Injections, Subcutaneous
  • Interferon-alpha / administration & dosage*
  • Leukopenia / chemically induced
  • Liver Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Oxonic Acid / administration & dosage*
  • Pilot Projects
  • Remission Induction
  • Survival Rate
  • Tegafur / administration & dosage*
  • Thrombocytopenia / chemically induced

Substances

  • Antimetabolites, Antineoplastic
  • Drug Combinations
  • Immunologic Factors
  • Interferon-alpha
  • S 1 (combination)
  • Tegafur
  • Oxonic Acid
  • Dihydrouracil Dehydrogenase (NADP)