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Targeting Vascular Endothelial Growth Factor in Advanced Carcinoid Tumor: A Random Assignment Phase II Study of Depot Octreotide With Bevacizumab and Pegylated Interferon Alfa-2b

James C. Yao, Alexandria Phan, Paulo M. Hoff, Helen X. Chen, Chusilp Charnsangavej, Sai-Ching J. Yeung, Kenneth Hess, Chaan Ng, James L. Abbruzzese, Jaffer A. Ajani

From the Departments of Gastrointestinal Medical Oncology, Diagnostic Imaging, General Internal Medicine, Ambulatory Treatment & Emergency Care and Biostatistics and Applied Mathematics, The University of Texas M.D. Anderson Cancer Center, Houston, TX; and the Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD

Corresponding author: James C. Yao, MD, Department of Gastrointestinal Medical Oncology, Unit 426, The University of Texas M.D. Anderson Cancer, 1515 Holcombe Blvd, Houston, TX 77030; e-mail: jyao{at}mdanderson.org

Purpose Effective systemic therapy for advanced carcinoid is lacking. The combination of bevacizumab (BEV) and pegylated (PEG) interferon alfa-2b was evaluated among patients with metastatic or unresectable carcinoid tumors.

Patients and Methods Forty-four patients on stable doses of octreotide were randomly assigned to 18 weeks of treatment with bevacizumab or PEG interferon alfa-2b. At disease progression (PD) or at the end of 18 weeks (whichever occurred earlier), patients received bevacizumab plus PEG interferon until progression. Functional computer tomography (CT) scans were performed to measure effect on tumor blood flow.

Results In the bevacizumab arm, four patients (18%) achieved confirmed partial response (PR), 17 patients (77%) had stable disease (SD), and one patient (5%) had PD. In the PEG interferon arm, 15 patients (68%) had SD and six patients (27%) had PD. Progression-free survival (PFS) rates after 18 weeks of monotherapy were 95% in bevacizumab versus 68% on the PEG interferon arm. The overall median PFS for all 44 patients is 63 weeks. Compared with paired baseline measurements on functional CT scans, we observed a 49% (P < .01) and 28% (P < .01) decrease in tumor blood flow at day 2 and week 18 among patients treated with bevacizumab. No significant changes in tumor blood flow were observed following PEG interferon. PEG interferon alfa-2b treatment was associated with decrease in plasma basic fibroblast growth factor (bFGF; P = .04) and increase in plasma interleukin-18 (IL-18; P < .01). No significant changes in bFGF or IL-18 following treatment with bevacizumab were observed.

Conclusion Bevacizumab therapy resulted in objective responses, reduction of tumor blood flow, and longer PFS in patients with carcinoid than PEG interferon treatment.

Supported in part by grants from National Cancer Institute (N01-CM-17003 and 22XSO94A), Schering Plough, and the American Society of Clinical Oncology. This trial was sponsored by Cancer Therapy Evaluation Program of NCI under the Clinical Research and Development Agreement (CRADA) with Genentech Inc.

Presented in part at the American Society of Clinical Oncology Annual Meeting, Orlando, FL, May 13-17, 2005, and the 9th International Symposium on Anti-angiogenic Agents, February 1 to 3, 2007, San Diego, CA.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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