Changes in shedding of soluble tumor necrosis factor receptors (sR1/R2) and in dynamic MRI as early predictors of outcome with NGR-hTNF.

e22145 Background: Dose-response curve of NGR-hTNF, a selective antivascular agent, is typically biphasic with activity shown either at low dose (LD) or high dose (HD). Receptor shedding may block drug activity. Vascular effects at LD are characterized by early vessel stabilization and late vessel damage, while at HD by rapid vessel disruption. Methods: 60 pts (median age: 61; M/F: 44/16; PS 0/≥1: 25/35; median prior lines: 3) received in 2 ph I trials NGR-hTNF at LD (0.2-1.6 µg/m2; n=14) or HD (60-325 µg/m2; n=46) every 3 weeks. We tested the impact of early changes (post 1st dose) in baseline-normalized plasma receptor levels (n=60) and in DCE-MRI-assessed Ktrans (n=49) on treatment effect, including disease control (DC, rate of pts progression free at 6 weeks by RECIST criteria) and progression free survival (PFS). Results: Baseline receptor levels were not related to outcome. Post-dosing levels of sR1 (median, 4.6 ng/mL; interquartile range, 2.8-5.7) and sR2 (8.6; 4.5-10.7) increased with dose (p<.000...