Bevacizumab plus gemcitabine and oxaliplatin as first-line therapy for metastatic or locally advanced pancreatic cancer: a phase II trial

Purpose The gemcitabine and oxaliplatin (GEMOX) has yielded among the longest progression-free survival durations in patients with advanced pancreatic cancer (APC). We postulated that adding bevacizumab would increase the effectiveness of GEMOX. Methods Eligible patients had stage III or IV pancreatic cancer, ECOG PS 0-2, and no prior gemcitabine. Treatment included 1,000 mg/m2 intravenous gemcitabine over 100 min on day 1, 10 mg/kg intravenous bevacizumab on day 1, and 100 mg/m2 oxaliplatin given on day 2. Cycles were repeated every 2 weeks. CT imaging was performed every 6 weeks. Results Fifty patients were enrolled: 14 had stage III disease, the remainder stage IV. Median age was 59 years. Fourty-five patients were ECOG 0-1. The grade 3–4 toxicity rate was 94%; fatigue (47%) and nausea (40%) were frequent. One patient died after a bowel perforation; a second died of a CVA. The median PFS was 4.9 months; median survival was 11.9 months; 1 year survival was 42%. Locally advanced patients lived 12.8 months; metastatic patients lived 10.2 months. Patients developing grade 3 hypertension were more likely to have a radiologic response (P = .012); survival among the top and bottom quintiles of hypertension was 14.7 and 6.2 months, respectively. Survival correlated with baseline CA 19–9 (P = .004) and radiologic response. The overall response rate was 36%; 34% demonstrated stable disease. Conclusions The GEMOX/bevacizumab regimen demonstrated an excellent median overall survival but did not meet our objective of a 14 month median survival. Toxicity was significant. We do not recommend further evaluation of this regimen.