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

Eisuke Murakami; Hiroshi Aikata; Daisuke Miyaki; Yuko Nagaoki; Yoshio Katamura; Tomokazu Kawaoka; Shintaro Takaki; Akira Hiramatsu; Koji Waki; Shoichi Takahashi; Tomoki Kimura; Masahiro Kenjo; Yasushi Nagata; Masaki Ishikawa; Hideaki Kakizawa; Kazuo Awai; Kazuaki Chayama

doi:10.1111/j.1872-034X.2011.00943.x

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

Hepatol Res. 2012 May;42(5):442-53. doi: 10.1111/j.1872-034X.2011.00943.x. Epub 2011 Dec 16.

Authors

Eisuke Murakami¹, Hiroshi Aikata, Daisuke Miyaki, Yuko Nagaoki, Yoshio Katamura, Tomokazu Kawaoka, Shintaro Takaki, Akira Hiramatsu, Koji Waki, Shoichi Takahashi, Tomoki Kimura, Masahiro Kenjo, Yasushi Nagata, Masaki Ishikawa, Hideaki Kakizawa, Kazuo Awai, Kazuaki Chayama

Affiliation

¹ Departments of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science Radiation Oncology, Division of Genome Radiobiology and Medical Science Diagnostic Radiology, Division of Medical Intelligence and Informatics, Hiroshima University, Hiroshima, Japan.

PMID: 22176468
DOI: 10.1111/j.1872-034X.2011.00943.x

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.