VEGF A levels increased relative to baseline at cycle 1 day 28, while levels of all other proteins declined. The most marked changes were seen in levels of VEGF A, which increased by 193% above baseline at cycle selleck chemicals llc 1 day 28, and in sVEGFR 3, which decreased by 78. 1% at the same time point. Plasma levels of sVEGFR 2 and sKIT decreased by 54. 4% and 38. 0%, respectively, at cycle 1 day 28. For VEGF A, sVEGFR 2, and sVEGFR 3, these changes were partially or completely reversed during the 2 week off treatment period, with levels returning to near baseline by the start of cycle 2. In contrast, levels of VEGF C and Inhibitors,Modulators,Libraries sKIT declined progressively, with no return towards baseline during the off treatment period, before leveling off at the end of cycle 2.

Patients with median levels of VEGF C at baseline had significantly lower median baseline VEGF A than patients with above median baseline VEGF C, and baseline concen Inhibitors,Modulators,Libraries trations of VEGF C and VEGF A were moderately cor related by linear regression analysis. In patients with median baseline plasma VEGF C levels, little or no change occurred in plasma VEGF C from baseline at any time on study, whereas in patients with above median VEGF C at base line, a marked reduction in VEGF C levels was observed. Differences in VEGF C ratios to baseline were significant at all time points except cycle 1 day 14. Low baseline VEGF C levels were correlated with elevated VEGF A ratios to baseline at cycle 1 day Inhibitors,Modulators,Libraries 14, cycle 2 day 1, and cycle 2 day 28. No significant differences were seen in changes from baseline for sVEGFR 2, sVEGFR 3 or sKIT levels at any time point, after stratification by median baseline VEGF C.

Relationship between baseline biomarker levels and tumor response Based on Inhibitors,Modulators,Libraries RECIST assessment of tumor response, 1 patient achieved a partial response and 13 had stable disease for 12 weeks, yielding a disease control rate of 37. 8%. Thirteen patients did not experience Inhibitors,Modulators,Libraries disease control and 10 patients were not evalu able. Analysis of tumor response using the Choi criteria was performed in 26 patients, among whom 17 patients were respon ders and 9 were non responders according to these cri teria. Table 1 and Additional File 1, Figure S1 show that patients who experienced disease control by RECIST had a significantly higher median baseline VEGF C concen tration than those without disease control, with a trend towards higher VEGF C levels in Choi responders vs.

non responders. For VEGF A at baseline, patients with and without disease control had median baseline levels of 108. 7 and 46. 6 pg mL, respectively and VEGF A levels were also significantly ele vated in Choi responders. Baseline levels of sVEGFR 2, sVEGFR 3, and sKIT did not differ therefore signifi cantly when analyzed for disease control or by Choi response. ROC analysis was performed on baseline soluble pro tein levels as discriminators in predicting disease control versus PD, as assessed by RECIST.