Gemcitabine plus sorafenib in patients with advanced pancreatic cancer: a phase II trial of the University of Chicago Phase II Consortium

Invest New Drugs. 2012 Feb;30(1):382-6. doi: 10.1007/s10637-010-9526-z. Epub 2010 Aug 28.

Abstract

Background: Sorafenib, an inhibitor of B-raf, VEGFR2, and PDGFR-β, has activity against pancreatic cancer in preclinical models. In a phase I trial of gemcitabine plus sorafenib, 57% of pancreatic cancer patients achieved stable disease.

Patients and methods: We conducted a multi-center phase II trial of sorafenib plus gemcitabine in chemo-naïve patients with histologically-confirmed, advanced pancreatic cancer. Patients received sorafenib 400 mg twice daily and gemcitabine 1,000 mg/m(2) on days 1, 8 and 15 of a 28 day cycle.

Results: Seventeen patients enrolled at 4 centers; 13 were evaluable for response. There were no objective responses; 18% had stable disease. Median overall survival was 4.0 months (95% CI: 3.4, 5.9); median progression-free survival was 3.2 months (95% CI: 1.6, 3.6). Grade 3/4 toxicities included thrombosis in 18% of patients, dehydration or hand-foot syndrome in 12%, and hypertension or gastrointestinal bleeding in 6%.

Conclusion: Gemcitabine plus sorafenib is inactive in advanced pancreatic cancer.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Benzenesulfonates / administration & dosage
  • Chicago
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Disease-Free Survival
  • Drug Administration Schedule
  • Female
  • Gemcitabine
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Niacinamide / analogs & derivatives
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Phenylurea Compounds
  • Pyridines / administration & dosage
  • Sorafenib
  • Time Factors
  • Treatment Outcome
  • Universities

Substances

  • Benzenesulfonates
  • Phenylurea Compounds
  • Pyridines
  • Deoxycytidine
  • Niacinamide
  • Sorafenib
  • Gemcitabine