Changes in Plasma Vascular Endothelial Growth Factor at 8 Weeks After Sorafenib Administration as Predictors of Survival for Advanced Hepatocellular Carcinoma

BACKGROUND: A new predictive biomarker for determining prognosis in patients with hepatocellular carcinoma (HCC) who receive sorafenib is required, because achieving a reduction in tumor size with sorafenib is rare, even in patients who have a favorable prog-nosis. Vascular endothelial growth factor (VEGF) receptor is a sorafenib target. In the current study, the authors examined changes in plasma VEGF concentrations during sorafenib treatment and determined the clinical significance of VEGF as a prognostic indicator in patients with HCC. METHODS: Plasma VEGF concentrations were serially measured in 63 patients with advanced HCC before and during sorafenib treatment. A plasma VEGF concentration that decreased>5 % from the pretreatment level at 8 weeks was defined as a “VEGF decrease. ” An objective tumor response was determined using modified Response Evaluation Criteria in Solid Tumors 1 month after the initiation of therapy and every 3 months thereafter. RESULTS: Patients who had a VEGF decrease at week 8 (n5 14) had a longer median survival than those who did not have a VEGF decrease (n549; 30.9 months vs 14.4 months; P5.038). All patients who had a VEGF decrease survived for>6 months, and the patients who had both a VEGF decrease and an a-fetoprotein response (n56) survived during the observation period (median, 19.7 months; range, 6.5-31.0 months). In univariate analyses, a VEGF decrease, radiologic findings classified as progressive disease, and major vascular invasion were associated significantly with 1-year survival; and, in multivariate analysis, a VEGF decrease was identified as an independent factor associated significantly with survival. CONCLUSIONS: A plasma VEGF concentration decrease at 8 weeks after starting sorafenib treatment may predict favorable overal