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

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.
Hepatology Research (Impact Factor: 2.74). 12/2011; 42(5):442-53. DOI: 10.1111/j.1872-034X.2011.00943.x
Source: PubMed


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.

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    • "Radiotherapy (RT) can produce survival benefits in patients with advanced HCC and macroscopic hepatic vascular invasion [7,16-18]. We previously reported that the use of three-dimensional conformal RT (3D-CRT) resulted in a good disease control rate and prolonged survival in these patients. "
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    ABSTRACT: We examined whether treatment sequence and secondary therapy affected prognosis in advanced hepatocellular carcinoma (HCC) of Child-Pugh A without metastasis. The study included 148 patients: 83 who primarily received Hepatic Arterial Infusion Chemotherapy (HAIC), 53 who received Sorafenib, and 12 with best supportive care (BSC). These treatment groups were stratified by presence (+)/absence (-) of secondary therapy. Although a significant difference in the response rate was found between the HAIC group and the Sorafenib group, there were no differences in disease control rate and survival. Additionally, both prolonged survival compared to the BSC group. Sorafenib (+) group showed the highest cumulative survival rate, which was an independent prognostic factor in multivariate analysis. Furthermore, the initial Sorafenib dose per body weight was a contributing factor for treatability with HAIC as secondary therapy subsequent to Sorafenib. The prognosis of advanced HCC might be improved by Sorafenib per body weight followed by HAIC.
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