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/m2 per minute), cisplatin 20 mg/m2, 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 ≥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.