Effect of chemotherapy to the liver with pretreatment of interferon for hepatocellular carcinoma to aim at the acquisition of the sensitivity for anti-cancer drugs.

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We have detected hepatitis C virus (HCV) core protein induced the tolerance against the anti-cancer drugs. Interferon (IFN) is well known to decrease viral load of HCV. Percutaneous Isolated Hepatic Perfusion (PIHP) is a high dose chemotherapy to the liver, while reducing the systemic exposure of the cytotoxic drugs. We investigate the efficacy of the chemotherapy to the liver using PIHP with pretreatment of IFN for patients who has hepatocellular carcinoma (HCC) with HCV.(A)Basic study1)Analysis of the mechanism in the acquirement of the tolerance against anti-cancer drugs.We cultured HCV core protein expression cells and controlled cells in the medium including Actinomycin D (Act.D) or Doxorubicin (Doxo). CyclosporinA, which is a inhibitor of P-glycoprotein, suppress the survival of HCV core protein expression cells (Act.D ; 151%→10.2%, Doxo ; 86%→2.4%). P-glycoprotein is one of the mediators relating to the mechanism in the acquirement of the tolerance against anti-cancer drugs in the HCV core protein expression cells.(B)Clinical study1)Retrospecthe study : Patients treated by PIHP who had HCC with HCV were categorized into two groups according to the HCV-RNA levels. Group I ; HCV-RNA<3x10^2Kcopy/ml, GroupII ; HCV-RNA≧3x10^2Kcopy/ml. We compared the tumor effect between group I and II. Local tumor control was significantly effective in group I compared with group II. CR+PR ; 86% in group I vs 25% in group II2)Prospective study : We produced the protocol of the pretreatment of IFN-α (IFN-α 300 x 10^4 IU/day, everyday, 1week). PIHP was performed in 2 cases after pretreatment of IFN. These 2 cases has partial response after 1 month of PIHP. Based on these results, pretreatment of IFN increases the sensitivity of anti-tumor drugs in HCC patients with HCV However, pancytopenia which is a side effect of IFN is the most problem to be improved.