Serum Insulin-Like Growth Factor-1 Levels Predict Outcomes of Patients with Advanced Hepatocellular Carcinoma Receiving Antiangiogenic Therapy

Abstract

Purpose: Patients with liver cirrhosis or hepatocellular carcinoma (HCC) have decreased serum insulin-like growth factor (IGF)-1 levels. We evaluated whether IGF-1 levels were associated with the outcomes of patients with advanced HCC treated with systemic antiangiogenic therapy. Experimental Design: The study was based on patients with advanced HCC who were enrolled in two clinical trials evaluating first-line combination antiangiogenic therapy. Serum samples were collected before treatment and four to six weeks after the start of treatment. The levels of IGF-1, IGF-2, and IGF-binding protein-3 (IGFBP3) were analyzed for their associations with treatment outcomes. Results: A total of 83 patients were included in the study. Patients who had high (≥the median level) baseline IGF-1 levels had significantly higher disease control rate (DCR) than patients who had low (P = 0.003). The levels of posttreatment IGF-1, and pre- or posttreatment IGF-2 and IGFBP3 were not associated with DCR. Patients with high baseline IGF-1 levels, compared with patients with low levels, had significantly longer progression-free survival (PFS; median, 4.3 vs. 1.9 months, P = 0.014) and overall survival (OS; median, 10.7 vs. 3.9 months, P = 0.009). The high baseline IGF-1 level remains an independent factor associated with favorable PFS and OS in multivariate analysis. Conclusions: High pretreatment IGF-1 levels were associated with better DCR, PFS, and OS of patients who received antiangiogenic therapy for advanced HCC. This finding warrants validation in large studies. Clin Cancer Res; 18(14); 3992–7. ©2012 AACR.