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Phase II Trial of Bevacizumab Plus Gemcitabine in Patients With Advanced Pancreatic Cancer

From the Section of Hematology/Oncology, University of Chicago Medical Center; Cancer Research Center; Department of Health Studies; Department of Radiology, University of Chicago, Chicago; Evanston Hospital, Evanston; Ingalls Hospital, Harvey, IL; Fort Wayne Medical Center, Fort Wayne; and Northern Indiana Cancer Research Consortium, South Bend, IN

Address reprint requests to Hedy Lee Kindler, MD, University of Chicago Medical Center, Section of Hematology/Oncology, 5841 S Maryland Ave, MC 2115, Chicago, IL 60637-1470; e-mail: hkindler{at}medicine.bsd.uchicago.edu

PURPOSE: Vascular endothelial growth factor (VEGF) plays a key role in the biology and prognosis of pancreatic cancer. Inhibitors of VEGF suppress the growth of pancreatic cancer in preclinical models. The objectives of this phase II study were to assess the response rate and overall survival of pancreatic cancer patients who received gemcitabine with the recombinant humanized anti-VEGF monoclonal antibody bevacizumab.

PATIENTS AND METHODS: Patients with previously untreated advanced pancreatic cancer received gemcitabine 1,000 mg/m² intravenously over 30 minutes on days 1, 8, and 15 every 28 days. Bevacizumab, 10 mg/kg, was administered after gemcitabine on days 1 and 15. Tumor measurements were assessed every two cycles. Plasma VEGF levels were obtained pretreatment.

RESULTS: Fifty-two patients were enrolled at seven centers between November 2001 and March 2004. All patients had metastatic disease, and 83% had liver metastases. Eleven patients (21%) had confirmed partial responses, and 24 (46%) had stable disease. The 6-month survival rate was 77%. Median survival was 8.8 months; median progression-free survival was 5.4 months. Pretreatment plasma VEGF levels did not correlate with outcome. Grade 3 and 4 toxicities included hypertension in 19% of the patients, thrombosis in 13%, visceral perforation in 8%, and bleeding in 2%.

CONCLUSION: The combination of bevacizumab plus gemcitabine is active in advanced pancreatic cancer patients. Additional study is warranted. A randomized phase III trial of gemcitabine plus bevacizumab versus gemcitabine plus placebo is ongoing in the Cancer and Leukemia Group B.

Supported by National Cancer Institute Grant No. N01-CM-17102.

Presented in part at the 39th Annual Meeting of the American Society of Clinical Oncology, May 31-June 3, 2003, Chicago, IL; 40th Annual Meeting of the American Society of Clinical Oncology, June 5-8, 2004, New Orleans, LA; and the American Society of Clinical Oncology Gastrointestinal Cancer Symposium, January 22-24, 2004, San Francisco, CA.

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

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