A phase II study evaluating bevacizumab in combination with fixed-dose rate gemcitabine and low-dose cisplatin for metastatic pancreatic cancer: is an anti-VEGF strategy still applicable?
BACKGROUND
The role of bevacizumab, a recombinant humanized monoclonal antibody directed against vascular endothelial growth factor, in the treatment of pancreatic cancer remains unclear. The objectives of this study were to determine safety and efficacy in chemotherapy-naive patients with metastatic pancreatic cancer receiving bevacizumab in combination with fixed-dose rate (FDR) gemcitabine and low-dose cisplatin.


METHODS
Eligible patients received gemcitabine 1,000 mg/m2 at FDR infusion (10 mg/m(2) per minute), cisplatin 20 mg/m(2), and bevacizumab 10 mg/kg, on days 1 and 15 of a 28-day cycle. Patients were monitored by computed tomography scans every two cycles and monthly serum CA19-9 measurements.


RESULTS
Of 52 patients eligible for analysis, ten (19.2%) had an unconfirmed response and 30 (57.7%) had stable disease. Of 35 patients with elevated baseline CA19-9 levels, 20 (57.1%) had > or = 50% biomarker decline during treatment. Median time to tumor progression was 6.6 months and median survival was 8.2 months (estimated 1-year survival, 36%). Grade 3/4 toxicities possibly related to bevacizumab included thromboembolic events (15.1%), hypertension (13.2%), gastrointestinal bleeding (9.4%), cardiac events (7.5%), and bowel perforation (5.7%). Plasma vascular endothelial growth factor and basic fibroblast growth factor levels and circulating tumor cell concentration did not correlate with overall survival, either at baseline or after 2 months of therapy.


CONCLUSIONS
This bevacizumab-containing study regimen is modestly effective in patients with metastatic pancreatic cancer, although occasional serious complications may occur. Given the negative results of CALGB 80303, future efforts should be focused on identifying those specific patients who are most likely to benefit from bevacizumab-based therapy.
Ko
Andrew H
AH
University of California at San Francisco Comprehensive Cancer Center, 1600 Divisadero Street, 4th floor, Box 1705, San Francisco, CA, 94115, USA. andrewko@medicine.ucsf.edu
Dito
Elizabeth
E
Schillinger
Brian
B
Venook
Alan P
AP
Xu
Zhidong
Z
Bergsland
Emily K
EK
Wong
Derrick
D
Scott
Janet
J
Hwang
Jimmy
J
Tempero
Margaret A
MA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D002945:Cisplatin / Q000008:administration & dosage*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D000093542:Gemcitabine
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D003841:Deoxycytidine; D000068258:Bevacizumab; D002945:Cisplatin; D000093542:Gemcitabine