Combined Intra-Arterial 5-Fluorouracil and Subcutaneous Interferon-Alpha Therapy for Advanced Hepatocellular Carcinoma with Tumor Thrombi in the Major Portal Branches

  • Morito Monden
  • Masato Sakon
  • Hiroaki Nagano
Conference paper


In the last 2 decades, there were marked progresses in the treatment of hepatocellular carcinoma (HCC) especially in Japan. Many different modalities were devised such as surgical resection, trans-arterial embolization (TAE), percutaneous ethanol injection (PEI), microwave coagulation therapy (MCT) and radio-frequency ablation (RFA) (Figure 1). However, the prognosis of advanced HCC remains poor, particularly in patients with tumor thrombi in the major branches of the portal vein (Vp3). Almost all patients with unresectable tumors die within several months with poor quality of life due to intractable ascites or esophageal bleeding. Even in resectable cases, the prognosis is extremely poor despite aggressive surgery. Furthermore, conventional therapies generally are not indicated for HCC with portal tumor thrombi due to lack of efficacy and possible complications. Arterial infusion chemotherapy also has been attempted, but its effectiveness is still unsatisfactory. Urabe et al. [1] have reported that administration of interferon-alpha (INF-alpha) with multiple anticancer drugs such as 5- fluorouracil (5-FU), cisplatin (CDDP), methotrexate (MTX) and leucovorin was effective in HCC patients with Vp3. However, myelosuppressive adverse effects, severe leucopenia or thrombocytopenia occurred in almost all patients, indicating that this regimen is not practical despite the excellent anti-tumor effect. To design a simple combination therapy from above regimen, with less adverse effect, we developed just subcutaneous INF-alpha and intra-arterial 5-FU administration. The response rate is in this series of patients was as high as that reported by Urabe et al, who used the full regimen. Another advantage of this combination therapy is the markedly low incidence of myelosuppressive side effects.


HuH7 Cell Tumor Thrombus Percutaneous Ethanol Injection Advance Hepatocellular Carcinoma Severe Leucopenia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Urabe T, Kaneko S, Matsushita E, Unoura M, Kobayashi K. Clinical pilot study of intrahepatic arterial chemotherapy with methotrexate, 5-fluorouracil, cisplatin and subcutaneous interferon-alpha-2b for patients with locally advanced hepatocellular carcinoma. Oncology 1998;55:39–47.PubMedCrossRefGoogle Scholar
  2. 2.
    Miyamoto A, Umeshita K, Sakon M, et al. Advanced hepatocellular carcinoma with distant metastases, successfully treated by a combination therapy of a-interferon and oral tegafur/uracil. J Gastroenterol Hepatol 2000;15:1447–1451.PubMedCrossRefGoogle Scholar
  3. 3.
    Eguchi, H, Nagano H, Sakon M, et al. Augmentation of antitumor activity of 5fluorouracil by interferon alpha is associated with up-regulation of p27Kip1 in human hepatocellular carcinoma cells. Clin Cancer 2000;Res6(7):2881–90.Google Scholar
  4. 4.
    Ito Y, Matsuura N, Sakon M, et al. Expression and prognostic roles of the G1-S modulators in hepatocellular carcinoma: p27 independently predicts the recurrence. Hepatology 1999;30:90–99.PubMedCrossRefGoogle Scholar
  5. 5.
    Yano H, Iemura A, Haramaki M, et al. Interferon alpha receptor expression and growth inhibition by interferon a in human liver cancer cell lines. Hepatology 1999;29:17081717.Google Scholar
  6. 6.
    Kondo M, Nagano H, Sakon M, et al. Expression of interferon alpha/beta receptor in human hepatocellular carcinoma. Int J Oncol 2000;17(1):83–88.PubMedGoogle Scholar

Copyright information

© Springer Japan 2004

Authors and Affiliations

  • Morito Monden
    • 1
  • Masato Sakon
    • 1
  • Hiroaki Nagano
    • 1
  1. 1.Department of Surgery and Clinical OncologyOsaka University, Graduate School of MedicineOsakaJapan

Personalised recommendations