Bevacizumab plus gemcitabine and oxaliplatin as first-line therapy for metastatic or locally advanced pancreatic cancer: a phase II trial
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.
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.
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.
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.
KeywordsPancreatic cancer Adenocarcinoma Pharmacotherapy Antibodies Monoclonal Clinical trial Chemotherapy
- 7.Berlin JD, Catalano P, Thomas JP, Kugler JW, Haller DG, Benson AB (2002) Phase III study of gemcitabine in combination with fluorouracil versus gemcitabine alone in patients with advanced pancreatic carcinoma: eastern cooperative oncology group trial E2297. J Clin Oncol 20:3270–3275PubMedCrossRefGoogle Scholar
- 11.Poplin E, Feng Y, Berlin J et al (2009) Phase III, randomized study of gemcitabine and oxaliplatin versus gemcitabine (fixed-dose rate infusion) compared with gemcitabine (30 min infusion) in patients with pancreatic carcinoma E7201: a trial of the eastern cooperative oncology group. J Clin Oncol 27:3778–3785PubMedCrossRefGoogle Scholar
- 15.Cox DR (1972) Regression models and life tables. J R Stat Soc A 29:187–220Google Scholar
- 17.Kindler HL, Niedzwiecki D, Hollis D et al (2007) A double-blind, placebo controlled, randomized phase III trial of gemcitabine (G) plus bevacizumab (B) versus gemcitabine plus placebo (P) in patients (pts) with advanced pancreatic cancer (PC): a preliminary analysis of cancer and leukemia group B (CALGB) 80303. J Clin Oncol 25:18s (suppl; abstr 4508)Google Scholar
- 19.Conroy T, Desseigne F, Ychou M et al (2010) Randomized phase III trial comparing FOLFIRINOX (F: 5FU/leucovorin [LV], irinotecan [I], and oxaliplatin [O]) versus gemcitabine (G) as first-line treatment for metastatic pancreatic adenocarcinoma (MPA): Preplanned interim analysis results of the PRODIGE 4/ACCORD 11 trial. J Clin Oncol 28:15s (suppl, Abstr 4010)Google Scholar
- 20.Fine RL, Fogelman DR, Schreibman SM, Desai M, Sherman W, Strauss J, Guba S, Andrade R, Chabot J (2008) The gemcitabine, docetaxel, and capecitabine (GTX) regimen for metastatic pancreatic cancer: a retrospective analysis. Cancer Chemother Pharmacol 61(1):165–167Google Scholar
- 24.Friberg G, Kasza K, Vokes E, Kindler H (2005) Early Hypertension as a potential pharmacodynamic (PD) marker for survival in pancreatic cancer (PC) patients (pts) treated with bevacizumab (B) and gemcitabine (G). J Clin Oncol 23(16S):3020Google Scholar