Hepatic arterial infusion chemotherapy using 5-fluorouracil and systemic interferon-α for advanced hepatocellular carcinoma in combination with or without three-dimensional conformal radiotherapy to venous tumor thrombosis in hepatic vein or inferior vena cava

Authors

  • Eisuke Murakami,

    1. Departments of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science
    Search for more papers by this author
  • Hiroshi Aikata,

    Corresponding author
    1. Departments of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science
    Search for more papers by this author
  • Daisuke Miyaki,

    1. Departments of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science
    Search for more papers by this author
  • Yuko Nagaoki,

    1. Departments of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science
    Search for more papers by this author
  • Yoshio Katamura,

    1. Departments of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science
    Search for more papers by this author
  • Tomokazu Kawaoka,

    1. Departments of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science
    Search for more papers by this author
  • Shintaro Takaki,

    1. Departments of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science
    Search for more papers by this author
  • Akira Hiramatsu,

    1. Departments of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science
    Search for more papers by this author
  • Koji Waki,

    1. Departments of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science
    Search for more papers by this author
  • Shoichi Takahashi,

    1. Departments of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science
    Search for more papers by this author
  • Tomoki Kimura,

    1. Radiation Oncology, Division of Genome Radiobiology and Medical Science
    Search for more papers by this author
  • Masahiro Kenjo,

    1. Radiation Oncology, Division of Genome Radiobiology and Medical Science
    Search for more papers by this author
  • Yasushi Nagata,

    1. Radiation Oncology, Division of Genome Radiobiology and Medical Science
    Search for more papers by this author
  • Masaki Ishikawa,

    1. Diagnostic Radiology, Division of Medical Intelligence and Informatics, Hiroshima University, Hiroshima, Japan
    Search for more papers by this author
  • Hideaki Kakizawa,

    1. Diagnostic Radiology, Division of Medical Intelligence and Informatics, Hiroshima University, Hiroshima, Japan
    Search for more papers by this author
  • Kazuo Awai,

    1. Diagnostic Radiology, Division of Medical Intelligence and Informatics, Hiroshima University, Hiroshima, Japan
    Search for more papers by this author
  • Kazuaki Chayama

    1. Departments of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science
    Search for more papers by this author

Dr Hiroshi Aikata, Department of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, 1-2-3 Kasumi, Minamiku, Hiroshima 734-8551, Japan. Email: aikata@hiroshima-u.ac.jp

Abstract

Aim:  We investigated the efficacy of hepatic arterial infusion chemotherapy (HAIC) using 5-fluorouracil (5-FU) and systemic interferon (IFN)-α (HAIC-5-FU/IFN) for advanced hepatocellular carcinoma (HCC) with venous tumor thrombosis (VTT) in the hepatic vein trunk (Vv2) or inferior vena cava (Vv3).

Methods:  Thirty-three patients with HCC/Vv2/3 underwent HAIC with 5-FU (500 mg/body weight/day, into hepatic artery on days 1–5 on the first and second weeks) and IFN-α (recombinant IFN-α-2b 3 000 000 U or natural IFN-α 5 000 000 U, intramuscularly on days 1, 3 and 5 of each week). Three-dimensional conformal radiotherapy (3D-CRT) was used in combination with HAIC-5-FU/IFN in 14 of 33 patients to reduce VTT.

Result:  The median survival time (MST) was 7.9 months, and 1- and 2-year survival rates were 30% and 20%, respectively. Evaluation of intrahepatic response after two cycles of HAIC-5-FU/IFN showed complete response (CR) in three (9%) and partial response (PR) in seven (21%), with an objective response rate of 30%. Multivariate analysis identified reduction of VTT (P = 0.0006), size of largest tumor (P = 0.013) and intrahepatic response CR/PR (P = 0.030) as determinants of survival. CR/PR correlated significantly with tumor liver occupying rate (P = 0.016) and hepatitis C virus Ab (P = 0.010). Reduction of VTT correlated significantly with radiotherapy (P = 0.021) and platelet count (P = 0.015). Radiotherapy-related reduction in VTT significantly improved survival of 16 patients with Vv3 and non-CR/PR response of HAIC-5-FU/IFN (P = 0.028).

Conclusion:  As for advanced HCC with VTT of Vv2/3, HAIC-5-FU/IFN responsive patients could obtain favorable survival. Despite ineffective HAIC-5-FU/IFN, the combination with effective radiotherapy to VTT might improve patients' prognosis.

Ancillary