We have carried out a stratified phase II study of
sorafenib (So) in patients with advanced
angiosarcoma (n = 32) and
epithelioid hemangioendothelioma (n = 13). This report concerns the correlative analysis of the predictive values of circulating pro/anti-angiogenetic
biomarkers. Using the ELISA method (R&D Systems), circulating
biomarkers (
VEGF-A, in picograms per milliliter), thrombospondin-1 (TSP1, in micrograms per milliliter),
stem cell factor (SCF, in picograms per milliliter), placental
growth factor (PlGF, in picograms per milliliter),
VEGF-C (in picograms per milliliter), and
E-selectin (in nanograms per milliliter) were measured before So treatment and after 7 days.
VEGF-A (mean value 475 vs. 541, p = 0.002), TSP1 (16 vs. 24, p = 0.0002), and PlGF (20.9 vs. 40.7, p = 0.0001) significantly increased during the treatment. Treatment did not affect the levels of SCF,
VEGF-C, and
E-selectin. Only two
biomarkers were associated with better outcome as follows:
VEGF-A and PlGF. Best objective response and non-progression at 180 days were associated with low level of
VEGF-A at baseline (p = 0.04 and 0.03, respectively). There was a correlation between the circulating level of
VEGF-A and time to progression (
TTP) (r = -0.47, p = 0.001). Best objective response and non-progression at 180 days were not associated with baseline level of PIGF, but there was a correlation between the circulating level of PIGF at baseline and
TTP. Low level of
VEGF-A at baseline (<500) was significantly associated with better outcome.