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

Abstract

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.