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 prognosis. 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 (n=14) had a longer median survival than those who did not have a VEGF decrease (n=49; 30.9 months vs 14.4 months; P=.038). All patients who had a VEGF decrease survived for >6 months, and the patients who had both a VEGF decrease and an α-fetoprotein response (n=6) 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 overall survival in patients with advanced HCC.

Early decrease in α-fetoprotein, but not des-γ-carboxy prothrombin, predicts sorafenib efficacy in patients with advanced hepatocellular carcinoma.

OBJECTIVES: The aim of this study was to investigate the relationships between early changes in the tumor markers α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP), and antitumor response in the early period following administration of sorafenib in patients with advanced hepatocellular carcinoma (HCC). METHODS: Forty-eight advanced HCC patients were evaluated. AFP and DCP were measured at baseline, and after 2 and 4 weeks, and the antitumor responses were evaluated according to the RECIST criteria 4 weeks after starting sorafenib therapy. The ratios of each tumor marker were compared by stratifying the patients into the partial response (PR) + stable disease (SD) group or the progressive disease (PD) group. RESULTS: Both 2 and 4 weeks after starting sorafenib therapy, the AFP ratio in the PR + SD group (n = 32) was significantly lower than in the PD group (n = 16; p = 0.002, p = 0.002). DCP was elevated in both the PR + SD group and the PD group 2 weeks and 4 weeks after starting sorafenib therapy. CONCLUSIONS: Evaluation of AFP ratios 2 and 4 weeks after starting sorafenib therapy may be useful for predicting antitumor response. On the other hand, early elevation of DCP does not necessarily suggest treatment failure by sorafenib, as DCP elevation can occur despite therapeutic efficacy.