Evaluation of serum/plasma VEGF/e-selectin and 18F-FDG PET uptake after panitumumab infusion in locally advanced rectal cancer (LARC) patients treated with chemoradiation (CTRT) (StarPan/STAR-02 phase II study).

Abstract

3654 Background: The aim of this study was to characterize the changes in circulating VEGF/E-Selectin and 18F-FDG PET uptake produced by panitumumab-based CTRT in LARC pts. Methods: The pts entering the study had rectal adenocarcinoma, cT3N+ or cT4N-/+ stage, with location < 12 cm from the anal margin. Panitumumab was administered at a dose of 6 mg/kg IV, 2 weeks before the start of CTRT, and then in combination with CTRT, 3 times every 2 weeks. CT consisted of 5FU 225 mg/m2/day CI IV days 1-38 and OXA 60 mg/m2 IV weekly six times. RT was delivered at a dose of 50.4 Gy. Rectal surgery was performed 7-8 weeks after the end of CTRT. Serum/plasma VEGF and sE-Selectin levels were determined on day -14 (baseline) and on days 1 (after panitumumab), 8 and 22 (during treatment), and 36 (pre-surgery). Biomarkers levels were assessed using commercial quantitative sandwich enzyme immunoassays (Quantikine Human VEGF Immunoassay, R&D Systems; Human sE-selectin ELISA, Bender MedSystems). 18F-FDG-PET scan evaluation was performed at baseline, after the first panitumumab administration (on days -1, -2). Results: Sixty-two pts were enrolled from February 2007 to October 2009. Pt characteristics were: males 34 (54.8%), females 28 (45.2%); median age 59 (38-73); clinical stage: T3 46 (74.6%), T4 16 (25.4%), N- 8 (13.6%), N+ 54 (86.4%). Twenty-four pts, enrolled in two Centers, were available for VEGF/E-Selectin evaluations and 25 pts for PET study. The mean basal values of biomarkers (at day -14) were: serum VEGF 439.1 pg/mL, plasma VEGF 177.2 pg/mL, serum sE-Selectin 37.5 ng/mL. On day 1 the VEGF and sE-Selectin mean value presented higher levels as compared with baseline: serum VEGF +41.7% (p = 0.047), plasma VEGF +129.6% (p = 0.708), sE-Selectin +50.6% (p < 0.001). The median SUV of PET scan decreased from 14 (range 6.1-26.9) at baseline to 10.5 (range 1.9-25.2) after panitumumab administration (p = 0.005). Conclusions: In these preliminary data, panitumumab monotherapy increased plasma/serum VEGF and sE-Selectin and decreased the 18F-FDG uptake. The results of the tumor pathological response will be available for the 2010 ASCO Meeting. No significant financial relationships to disclose.