Evaluation of newly developed combination therapy of intra‐arterial 5‐fluorouracil and systemic pegylated interferon α‐2b for advanced hepatocellular carcinoma with portal venous invasion: preliminary results

Ushio

et al. 2011

Cancer

Self Cite

BACKGROUND:The prognosis of advanced hepatocellular carcinoma (HCC) remains poor, particularly among patients with portal vein tumor thrombosis (PVTT). This study evaluated the efficacy of combined 5-fluorouracil and pegylated interferon (PEG-IFN) a-2b in patients with advanced HCC. METHODS: Subjects comprised 59 HCC patients with PVTT treated using subcutaneous administration of PEG-IFNa-2b (50-100 lg on day 1 of each week for 4 weeks) and intra-arterial infusion of 5-fluorouracil (250 mg/d for 5 hours on days 1-5 of each week for 4 weeks). One treatment cycle lasted 4 weeks. The current therapy was discontinued in patients with progressive disease (PD). For responses other than PD, treatment was repeated for !1 cycle. The primary efficacy endpoint was the objective early response rate. Secondary efficacy endpoints were progression-free survival (PFS) and overall survival. RESULTS: Objective early response rate was 73.0%. Cumulative PFS rates were 67.4% at 6 months, 30.2% at 12 months, 25.9% at 18 months, and 20.7% at 24 months. Median PFS was 9.7 months. Cumulative survival rates were 82.4% at 6 months, 73.6% at 12 months, 52.8% at 24 months, and 44.0% at 36 months. Median survival time was 29.9 months. All adverse reactions were controllable by temporary suspension of treatment. Serious complications and treatmentrelated deaths were not observed. CONCLUSIONS: Although a prospective randomized controlled trial using a larger population of patients with advanced HCC is needed to evaluate combination therapy with 5-fluorouracil and PEGIFNa-2b, this new combination therapy may be useful for patients with advanced HCC. Cancer 2012;118:3302-10.

Section: Introductionmentioning

confidence: 99%

Therapeutic efficacy of combination therapy with intra‐arterial 5‐fluorouracil and systemic pegylated interferon α‐2b for advanced hepatocellular carcinoma with portal venous invasion

Ushio

et al. 2011

Cancer

Self Cite

“…In 1999, Yano et al compared the in vivo antitumor effects of PEG-IFN-α2b and IFN-α in nude mice injected with cultured HCC cells, and found that PEG-IFN-α2b induced apoptosis more strongly than IFN-α [43]. Intra-arterial 5-FU infusion and systemic PEG-IFN-α2b combination therapy appears to be highly promising, although further prospective studies are required [42,44]. Reports of the use of HAIC with 5-FU combined with systemic IFN in advanced HCC are listed in Table 2.…”

Section: Chemotherapeutic Agentsmentioning

confidence: 99%

Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma in Japan

Nishikawa

Osaki

Kita

et al. 2012

Cancers

Transcatheter methods such as transcatheter arterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) have an important role in the treatment for advanced hepatocellular carcinoma (HCC). Recently, sorafenib, an inhibitor of tyrosine kinases, has been found to obtain survival benefits in patients with HCC, leading to major advances in the treatment of advanced HCC. However, it is associated with a low tumor response rate, minimal survival advantage, and high rates of adverse events. On the other hand, high rates of objective treatment response with HAIC for advanced HCC have been reported, although convincing evidence of it contributing to overall survival in HAIC has been lacking. In Japan, HAIC still tends to be the preferred method for the treatment of advanced HCC, even in patients with poor liver function. However, the choice of chemotherapeutic agents in TACE/HAIC for HCC varies between institutions. In this review, based on studies reported to date in the literature, we refer to current knowledge regarding the chemotherapeutic agents used for TACE/HAIC for HCC in Japan and consider the future perspectives for HAIC for this cancer.

J of Gastro and Hepatol

“…21 Each patient received an intra-arterial infusion of 5-FU (Kyowa Hakko Company, Tokyo, Japan) and subcutaneous PEG-IFNa-2b (PEG-Intron; MSD, Tokyo, Japan) or natural IFN-a (OIFs; Otsuka Pharmaceuticals Co., Tokyo, Japan); this combination therapy is henceforth referred to as 5-FU/IFN therapy. 6,9 One cycle of treatment lasted 4 weeks. 5-FU was administered into the hepatic artery over 5 h on days 1-5 of the first and second week of each 4-week cycle (500 mg/day).…”

Section: Treatment Protocolmentioning

confidence: 99%

“…Several studies have indicated the beneficial effect of a combination of intra-arterial 5-fluorouracil (5-FU) and systemic interferon-alpha (IFN-a) or pegylated interferon alpha-2b (PEG-IFNa-2b) for HCC with PVTT. [5][6][7][8][9] Recently, combination therapy that includes hepatic arterial infusion chemotherapy (HAIC) and three-dimensional conformal radiotherapy (3D-CRT) has been reported in patients with HCC and PVTT. 9 Advances in 3D-CRT have allowed more accurate delivery of higher radiation doses to the tumor, thus improving the antitumor effect and minimizing damage to normal tissue.…”

Section: Introductionmentioning

confidence: 99%

“…[5][6][7][8][9] Recently, combination therapy that includes hepatic arterial infusion chemotherapy (HAIC) and three-dimensional conformal radiotherapy (3D-CRT) has been reported in patients with HCC and PVTT. 9 Advances in 3D-CRT have allowed more accurate delivery of higher radiation doses to the tumor, thus improving the antitumor effect and minimizing damage to normal tissue. [10][11][12] However, it is difficult to increase the dose to the HCC when the tumor is in the liver, owing to the large respiratory movement of this organ.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Efficacy of therapy for advanced hepatocellular carcinoma: Intra‐arterial 5‐fluorouracil and subcutaneous interferon with image‐guided radiation

Chuma

Taguchi

Yamamoto

et al. 2011