Phase II and coagulation cascade biomarker study of bevacizumab with or without docetaxel in patients with previously treated metastatic pancreatic adenocarcinoma.

Authors

• Igor A Astsaturov
• Neal J Meropol
• R Katherine Alpaugh
• Barbara A Burtness
• Jonathan D Cheng
• Sue McLaughlin
• André Rogatko
• Zhiheng Xu
• James C Watson
• Louis M Weiner
• Steven J Cohen

Publication/Presentation Date

2-1-2011

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.

Volume

34

Issue

1

First Page

70

Last Page

75

ISSN

1537-453X

Published In/Presented At

Astsaturov, I. A., Meropol, N. J., Alpaugh, R. K., Burtness, B. A., Cheng, J. D., McLaughlin, S., Rogatko, A., Xu, Z., Watson, J. C., Weiner, L. M., & Cohen, S. J. (2011). 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, 34(1), 70–75. https://doi.org/10.1097/COC.0b013e3181d2734a

Disciplines

Medicine and Health Sciences

PubMedID

20458210

Department(s)

Hematology-Medical Oncology Division

Document Type

Article