Rapid decrease in blood flow (BF), blood volume (BV), and vascular permeability (PS) in carcinoid patients treated with bevacizumab

Abstract

3013 Background: Carcinoid tumors are vascular and frequently express VEGF. Effective systemic therapy is lacking. VEGF neutralizing antibodies decrease metastases in a carcinoid xenograft model. We are evaluating anti-angiogenic therapy in a phase II study of bevacizumab (BVZ) and PEG interferon alpha-2b (PEGI) in patients with metastatic or unresectable carcinoid tumors. Methods: Patients on a stable dose of octreotide are randomly assigned to BVZ or PEGI for 18 weeks. After initial 18 weeks, patients receive both BVZ and PEGI. Planned accrual is 44 patients. Functional CT (fCT) is used to monitor BF, BV, and PS. Results: Sixteen patients have been accrued; 8 patients have begun treatment on each arm. Radiological responses (1 PR and 1 MR) have been observed on BVZ therapy. One additional patient with SD had a 78% drop in urine 5HIAA level. Baseline and follow-up scans obtained 48 hours after the first dose of BVZ are being reported in the analysis of antiangiogenic effects. Rapid declines in tumor BF, BV, and PS were observed (Table). No significant change in mean transit time was observed. First follow-up fCT on the PEGI arm is performed at week 9. Due to the differing follow-up schedule, fCT data on the PEGI arm is available on only 2 patients at this time. No significant changes in BF, BV, and PS were observed. All patients remain on study and accrual is on going. Conclusions: BVZ treatment in carcinoid patients consistently produced rapid decline in tumor BF, BV, and PS. fCT in carcinoid may be an effective and non-invasive method for assessing target inhibition in VEGF directed anti-angiogenic therapy. No significant financial relationships to disclose.