Serum Insulin-Like Growth Factor-1 Levels Predict Outcomes of Patients with Advanced Hepatocellular Carcinoma Receiving Anti-Angiogenic Therapy
A partir des données de deux essais cliniques incluant au total 83 patients atteints d'un carcinome hépatocellulaire de stade avancé et recevant un traitement anti-angiogénique, cette étude montre une association entre les niveaux sériques du facteur de croissance analogue à l'insuline IGF-1 et la survie des patients
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 anti-angiogenic therapy. Experimental Design: The study was based on patients with advanced HCC who were enrolled in 2 clinical trials evaluating first-line combination anti-angiogenic therapy. Serum samples were collected before treatment and 4 to 6 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 (greater than or equal to) the median level) baseline IGF-1 levels had significantly higher disease control rate (DCR) than patients who had low (less the median level) levels (71% vs. 39%, p = 0.003). The levels of post-treatment IGF-1, and pre- or post-treatment IGF-2 and IGFBP3 were not associated with DCR. Patients with high baseline IGF-1 levels, compared to 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 pre-treatment IGF-1 levels were associated with better DCR, PFS and OS of patients who received anti-angiogenic therapy for advanced HCC. This finding warrants validation in large studies.
Clinical Cancer Research , résumé, 2012