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Astsaturov IA , Meropol NJ , Alpaugh RK , Burtness BA , Cheng JD , McLaughlin S , Rogatko A , Xu Z , Watson JC , Weiner LM , Cohen SJ
Phase II and coagulation cascade biomarker study of bevacizumab with or without docetaxel in patients with previously treated metastatic pancreatic adenocarcinoma
Am J Clin Oncol. 2011 Feb;34(1) :70-5
PMID: 20458210    PMCID: PMC3030655    URL: https://www.ncbi.nlm.nih.gov/pubmed/20458210
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PURPOSE: Treatment options are limited for advanced pancreatic cancer progressive after gemcitabine therapy. The vascular endothelial growth factor pathway is biologically important in pancreatic cancer, and docetaxel has modest antitumor activity. We evaluated the role of the anti-vascular endothelial growth factor antibody bevacizumab as second-line treatment for patients with metastatic pancreatic cancer. DESIGN: Patients with metastatic adenocarcinoma of the pancreas who had progressive disease on a gemcitabine-containing regimen were randomized to receive bevacizumab alone or bevacizumab in combination with docetaxel. RESULTS: Thirty-two patients were enrolled; 16 to bevacizumab alone (Arm A) and 16 to bevacizumab plus docetaxel (Arm B). Toxicities were greater in Arm B with the most common grade 3/4 nonhematologic toxicities including fatigue, diarrhea, dehydration, and anorexia. No confirmed objective responses were observed. At 4 months, 2 of the 16 patients in Arm A and 3 of the 16 patients in Arm B were free from progression. The study was stopped according to the early stopping rule for futility. Median progression-free survival and overall survival were 43 days and 165 days in Arm A and 48 days and 125 days in Arm B. Elevated d-dimer levels and thrombin-antithrombin complexes were associated with decreased survival and increased toxicity. CONCLUSION: Bevacizumab with or without docetaxel does not have antitumor activity in gemcitabine-refractory metastatic pancreatic cancer. Baseline and on-treatment d-dimer and thrombin-antithrombin complex levels are associated with increased toxicity and decreased survival.
Astsaturov, Igor A Meropol, Neal J Alpaugh, R Katherine Burtness, Barbara A Cheng, Jonathan D McLaughlin, Sue Rogatko, Andre Xu, Zhiheng Watson, James C Weiner, Louis M Cohen, Steven J eng P30 CA006927/CA/NCI NIH HHS/ P30 CA006927-44/CA/NCI NIH HHS/ Clinical Trial, Phase II Randomized Controlled Trial Research Support, N.I.H., Extramural Am J Clin Oncol. 2011 Feb;34(1):70-5. doi: 10.1097/COC.0b013e3181d2734a.