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

Abstract

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.

Comparison of hepatic arterial infusion chemotherapy and sorafenib in elderly patients with advanced hepatocellular carcinoma: A case series

“…Our findings were concurrent with those of previous studies of interferon-α-containing HAIC that demonstrated a RR of 24.6-73.0% (11,17,(20)(21)(22)(23)(24), indicating that interferon-α-containing HAIC is a feasible treatment for elderly patients with advanced HCC.…”

“…Multiple AEs have been associated with 5-FU, CDDP and interferon-α therapy; however, life-threatening AEs rarely occur, even in patients with liver cirrhosis (11,17,20,23). In this study, AEs in HAIC-treated patients were more severe than previously reported (11,17,20,23), particularly thrombocytopenia, although none resulted in treatment discontinuation or required any additional management. The evaluation of AEs in this patient population may be challenging, as the majority of the patients already presented with pancytopenia due to underlying liver cirrhosis.…”

Immunotherapeutic approaches for hepatocellular carcinoma

“…mOS of 29 months and 26 months were observed in the TACE-IFN-α and control group, respectively ( p = 0.003) [51]. A phase II trial evaluating the efficacy of combined intrarterial 5-fluorouracil (5-FU) and systemic pegylated IFN α-2b in patients with advanced HCC with portal venous invasion reported mOS of 29.9 months [52]. A meta-analysis of 10 trials (8 randomized and 2 non-randomized controlled studies) demonstrated that recurrence rate (RR) was significantly lower in patients treated with adjuvant IFN with respect to the placebo group (OR = 0.66; 95% CI = 0.50 to 0.86; p = 0.02).…”

Immunotherapy for hepatocellular carcinoma: From basic research to clinical use

“…IFN-α-2b also failed to decrease the risk of postoperative recurrence [18] . In contrast, interferon showed some benefits when combined with other modalities such as chemotherapy, curative resection and TACE [19][20][21][22] . Two meta-analyses revealed that adjuvant interferon therapy after curative therapy for HCC could improve both overall survival and recurrence-free survival [23,24] .…”