title: A randomized phase II of gemcitabine and sorafenib versus sorafenib alone in patients with metastatic pancreatic cancer.
abstract: OBJECTIVE
  Patients with metastatic pancreatic cancer have limited therapeutic options. The role of the Ras-Raf-MAPK pathway and of vascular endothelial growth factor in pancreatic carcinogenesis provided the rational to evaluate the efficacy of sorafenib with or without gemcitabine in a randomized phase II study.
  
  
  METHODS
  Patients with metastatic pancreatic cancer were randomized to sorafenib alone (arm A) or sorafenib with gemcitabine (arm B).
  
  
  RESULTS
  Arm A was closed to accrual at interim analysis due to the lack of objective response. Median PFS and OS were 2.3 and 4.3 months respectively. There was one partial response among the 37 patients in arm B. Median PFS and OS were 2.9 and 6.5 months respectively. There were more grade 3 and 4 toxicities in arm B with the most common being neutropenia (17%), thrombocytopenia (8%), alkaline phosphatase elevation (14%), venous thromboembolism (8%), diarrhea, hypokalemia and ALT elevation (5%) each. Several associations were noted between single nucleotide polymorphisms in ribonucleotide reductase, Cox-2, vascular endothelial growth factor and survival in patients treated with gemcitabine and sorafenib.
  
  
  CONCLUSIONS
  Neither sorafenib alone or sorafenib in combination with gemcitabine manifested promising activity in metastatic pancreatic cancer.
authors.affiliation: Division of Medical Oncology, Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Ave, Suite 3440, Los Angeles, CA 90033, USA. elkhouei@usc.edu
authors.forename: A B
authors.initials: AB
authors.lastname: El-Khoueiry
authors.forename: R K
authors.initials: RK
authors.lastname: Ramanathan
authors.forename: D Y
authors.initials: DY
authors.lastname: Yang
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.forename: S
authors.initials: S
authors.lastname: Shibata
authors.forename: J J
authors.initials: JJ
authors.lastname: Wright
authors.forename: D
authors.initials: D
authors.lastname: Gandara
authors.forename: H J
authors.initials: HJ
authors.lastname: Lenz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000009:adverse effects; D051546:Cyclooxygenase 2 / Q000235:genetics*; D003564:Cytidine Deaminase; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009536:Niacinamide / Q000031:analogs & derivatives; D009700:Nucleoside Deaminases / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010671:Phenylurea Compounds; D020641:Polymorphism, Single Nucleotide; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects; D012262:Ribonucleoside Diphosphate Reductase; D000077157:Sorafenib; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D000093542:Gemcitabine
chemical_list: D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D025521:Tumor Suppressor Proteins; D003841:Deoxycytidine; D009536:Niacinamide; D000077157:Sorafenib; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; D009700:Nucleoside Deaminases; D003564:Cytidine Deaminase; C011530:deoxycytidine deaminase; D000093542:Gemcitabine