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Astsaturov IA , Meropol NJ , Alpaugh RK , Burtness BA , Cheng JD , McLaughlin S , Rogatko A , Xu ZH , 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
American Journal of Clinical Oncology-Cancer Clinical Trials. 2011 Feb;34(1) :70-75
PMID: ISI:000286624100015    PMCID: PMC3030655   
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Abstract
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.
Notes
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. Genentech Inc. ; NIH [P30 CA006927]; Genentech Supported by Genentech Inc. and by the FCCC Core Grant P30 CA006927 from the NIH. Research funding from Genentech (to B. A. B.), and also consultancy to Genentech and Sanofi. 41 Lippincott williams & wilkins; 530 walnut st, philadelphia, pa 19106-3621 usa 711xf