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


METHODS
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.


CONCLUSIONS
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
IA
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111–2497, USA.
Meropol
Neal J
NJ
Alpaugh
R Katherine
RK
Burtness
Barbara A
BA
Cheng
Jonathan D
JD
McLaughlin
Sue
S
Rogatko
André
A
Xu
Zhiheng
Z
Watson
James C
JC
Weiner
Louis M
LM
Cohen
Steven J
SJ
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D015415:Biomarkers / Q000378:metabolism*; D001779:Blood Coagulation Factors / Q000378:metabolism*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D015996:Survival Rate; D016896:Treatment Outcome; D000093542:Gemcitabine
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D001779:Blood Coagulation Factors; D003841:Deoxycytidine; D000068258:Bevacizumab; D000093542:Gemcitabine
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