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

Cancer Chemother Pharmacol. 2011 Dec;68(6):1431-8. doi: 10.1007/s00280-011-1601-4. Epub 2011 Apr 9.

Abstract

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/m(2) intravenous gemcitabine over 100 min on day 1, 10 mg/kg intravenous bevacizumab on day 1, and 100 mg/m(2) 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.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Female
  • Gemcitabine
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Organoplatinum Compounds / administration & dosage
  • Oxaliplatin
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology

Substances

  • Antibodies, Monoclonal, Humanized
  • Organoplatinum Compounds
  • Oxaliplatin
  • Deoxycytidine
  • Bevacizumab
  • Gemcitabine