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Purpose: Insulin-like growth factor (IGF)-1 and its main binding protein, IGFBP-3, modulate cell growth, survival and angiogenesis by regulating vascular endothelial growth factor (VEGF). To investigate the clinical significance of pretreatment plasma levels of IGF-1, IGFBP-3, and VEGF in patients with advanced non-small cell lung cancer (NSCLC) underwent chemotherapy. Patients and Methods: Plasma levels of IGF-1, IGFBP-3, and VEGF were measured by enzyme-linked immunoassays in 77 patients enrolled in a phase II study of irinotecan plus cisplatin chemotherapy and compared with those of 11 healthy subjects. We also analyzed the association with clinicopathologic characteristics and treatment outcomes in NSCLC patients. Results: Plasma levels of IGF-1, IGFBP-3, and VEGF were significantly higher in NSCLC patients than healthy subjects (p=0.000, 0.037, and 0.001, respectively). In patients with NSCLC, IGFBP-3 level was significantly higher in female (p=0.017), age less than 59-year old (p=0.019), non-squamous cell carcinoma (p=0.013), never smoker (p=0.003), and inversely correlated with smoke exposure (p=0.001, r=-0.382). IGFBP-3 level was strongly correlated with IGF-1 level (r=0.514, p=0.000) and inversely correlated with VEGF level (r=-0.234, p=0.040). Patients with high plasma levels of IGF-1 and IGFBP-3 and low VEGF level had significantly longer progression-free (p=0.001, 0.003, and 0.010, respectively) and overall survival (p=0.002, 0.001, and 0.008, respectively). These remained statistically significant in multivariate analysis. Conclusions: Plasma levels of IGF-1, IGFBP-3, and VEGF are significantly increased in patients with advanced NSCLC and highly predictive of progression-free and overall survival, supporting independent prognostic values of those factors in NSCLC.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]

American Association for Cancer Research
2006