Prospective randomized controlled study of interferon‐alpha in preventing hepatocellular carcinoma recurrence after medical ablation therapy for primary tumors

Abstract

BACKGROUND Hepatocellular carcinoma (HCC) recurrence after ablation therapy for primary tumors is common. METHODS To evaluate the effectiveness of interferon‐alpha (IFN‐α) in preventing HCC recurrence, 30 eligible patients were randomized into three groups: 11 patients treated with three mega units (MU) of IFN‐α three times weekly for 24 months (IFN‐α‐continuous group), 9 patients treated with 3 MU of IFN‐α daily for 10 days every month for 6 months followed by 3 MU of IFN‐α daily for 10 days every 3 months for a further 18 months (IFN‐α‐intermittent group), and 10 patients who received no IFN‐α therapy (control group). The three groups were comparable in terms of etiology, demographics, and laboratory data at entry and HCC characteristics. RESULTS After a median follow‐up of 27 months (range 4–53 months), 9 patients (90%) in the control group and 9 patients (45%) in 2 treatment groups (6 patients in the IFN‐α‐continuous group and 3 patients in the IFN‐α‐intermittent group) developed an HCC recurrence (P = 0.021). Cumulative HCC recurrence rates in the IFN‐α‐intermittent, IFN‐α‐continuous, and control groups were 22.2%, 27.3%, and 40% at the end of 1 year and 33.3%, 54.6%, and 90% at the end of 4 years (P = 0.0375), respectively (control vs. IFN‐α‐intermittent group, P = 0.0123; vs. IFN‐α‐continuous group, P = 0.0822). If both IFN‐α groups were combined, the cumulative HCC recurrence rate of the patients treated with IFN‐α and the control group was 25% and 40% at the end of 1 year and 47% and 90% at the end of 4 years, respectively (P = 0.0135). CONCLUSIONS The data suggested that IFN‐α therapy may reduce HCC recurrence after medical ablation therapy for primary tumors. Cancer 2004;100:376–82. © 2003 American Cancer Society.

Effects of interferon alpha treatment on recurrence and survival after complete resection or ablation of hepatocellular carcinoma: A meta‐analysis of randomized controlled trials

“…As for data on overall early recurrence, we only extracted them from 5 articles 8,[30][31][32][33]35 because another article does not provide the essential data. 12 According to the methods we mentioned above, we extracted the number of 1 year recurrent events from 4 articles 8,[30][31][32][33] and that of 1.5 year recurrent events from another article in which the number of 1 year recurrent events was not available.…”

“…12 According to the methods we mentioned above, we extracted the number of 1 year recurrent events from 4 articles 8,[30][31][32][33] and that of 1.5 year recurrent events from another article in which the number of 1 year recurrent events was not available. 35 Moreover, we extracted data on overall survival from 5 articles 8,12,[30][31][32]35 because related data were not provided in another article, 33 while we only extracted the number of 1 year survival events from the 5 articles owing to some missing or incomplete data on 3 and 5 year survival. Results of the meta-analysis were as follows.…”

“…8,12,[30][31][32][33][34][35] Of the 8 studies, 3 were from the same research center 30,31,34 ; 1 of the 3, which did not provide the essential data, was excluded 34 ; in the remaining 2 studies that were by the same first author, the patients were the same, and some of the related data were also overlapping 30,31 ; moreover, each of the 2 studies 30,31 offered only part of the data that we wanted to extract, so to obtain full information, we combined the 2 studies and considered them as one. 30,31 Thus, finally 6 studies including 600 patients were included in this meta-analysis.…”

“…8,12,[30][31][32][33]35 Two studies were performed in China, 8,35 2 in Japan, 30-32 1 in 12 HCC was treated with resection before use of IFN-a in 4 studies, 8,12,30,31,35 and treated with ablation in 2 studies. 32,33 Resection as initial treatment for HCC was reported in 3 studies, 8,30,31,35 and resection with pre-resection ablation reported in 1 study. 12 In the 6 RCTs, all of the patients with HCC, proved mostly by pathology or histology, underwent therapies with complete resection or ablation; and IFN-a was used as adjuvant therapy initially after resection or ablation of HCC in each study.…”

“…8,12,[30][31][32][33][34][35] As far as early recurrence was concerned, some suggested that IFN-a could suppress early recurrence, 8,35 but others denied. 12,[30][31][32][33][34] As for survival, there were also discordant results reported 8,12,31,32,34,35 ; some concluded that IFN-a could improve survival, 8,31,32,34,35 but others demonstrated the opposite. 12 Considering the conflicting or inconclusive data, to reach a general conclusion, we conducted this meta-analysis with the first objective to evaluate the effect of IFN-a on overall early recurrence and survival after resection or ablation, and second to evaluate the impact of IFN-a on early recurrence and survival after liver resection that is the mainstay of treatment for primary liver cancers.…”