We read with interest the recent article by Ikeda et al. 1 and the accompanying editorial 2 on the use of interferon beta (IFN-โค) to prevent recurrent hepatocellular carcinoma (HCC) after treatment of the primary tumor. We offer comments from an oncologic perspective.
The investigators repeatedly note that the data were part of an ongoing trial but provided no details of that trial. It is important to know the full study design, particularly for evaluating marked differences in a small-scale trial. How long was the period of patient recruitment? How many patients were scheduled to be recruited, and what was the basis of the sample size calculation? How were patients randomized? What type of formal interim analysis was used? Who reviewed the interim data and recommended early termination? This information is necessary to assess the quality of the interim result.
The post-treatment recurrence rates among patients with no adjuvant therapy were much higher (62.5% at 1 year and 100% at 2 years) than those reported by others, suggesting an unrecognized bias in the randomization process. 2,3 Recurrence detected shortly after treatment has been presumed to represent intrahepatic metastasis. Therefore, if IFN-โค played a truly significant role as an adjuvant to local treatment, this agent should have shown antitumor activity against intrahepatic metastasis unrecognized at the initial treatment. However, an antitumor effect of IFN-โค for HCC has not been evaluated preclinically and was never established in a clinical setting. Thus, the rationale for IFN-โค as adjuvant therapy for HCC, remains unclear, even though IFN may prevent the development of second primary HCC in patients with hepatitis C virus-related HCC. 4,5 Prevention of recurrence after local treatment is of paramount importance to improve the long-term results for patients with HCC. Acyclic retinoid (polyprenoic acid) and iodine-131-labeled lipiodol have been evaluated in a prospective randomized manner and show promise as adjuvants to local treatment. 6,7 The current preliminary data, while promising, are not yet definitive. Prospective randomized trials, with patients stratified according to expected recurrence and survival, are mandatory to define the real role of IFN-โค as an adjuvant to local treatment for HCC.