title: Phase II randomised proof-of-concept study of the urokinase inhibitor upamostat (WX-671) in combination with gemcitabine compared with gemcitabine alone in patients with non-resectable, locally advanced pancreatic cancer.
abstract: BACKGROUND
  To evaluate the efficacy and tolerability of the urokinase plasminogen activator (uPA) inhibitor upamostat in combination with gemcitabine in locally advanced pancreatic adenocarcinoma (LAPC).
  
  
  METHODS
  Within a prospective multicenter study, LAPC patients were randomly assigned to receive 1000 mg m(-2) of gemcitabine IV weekly either alone (arm A) or in combination with 200 mg (arm B) or 400 mg (arm C) oral upamostat daily. Efficacy endpoints of this proof-of-concept study included response rate, time to first metastasis, progression-free and overall survival (OS).
  
  
  RESULTS
  Of the 95 enroled patients, 85 were evaluable for response and 93 for safety. Median OS was 12.5 months (95% CI 8.2-18.2) in arm C, 9.7 months (95% CI 8.4-17.1) in arm B and 9.9 months (95% CI 7.4-12.1) in arm A; corresponding 1-year survival rates were 50.6%, 40.7% and 33.9%, respectively. More patients achieved a partial remission (confirmed responses by RECIST) with upamostat combination therapy (arm C: 12.9%; arm B: 7.1%; arm A: 3.8%). Overall, only 12 patients progressed by developing detectable distant metastasis (arm A: 4, arm B: 6, arm C: 2). The most common adverse events considered to be related to upamostat were asthenia, fever and nausea.
  
  
  CONCLUSIONS
  In this proof-of-concept study targeting the uPA system in LAPC, the addition of upamostat to gemcitabine was tolerated well; similar survival results were observed for the three treatment arms.
authors: Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, D-81377 Munich, Germany. volker.heinemann@med.uni-muenchen.de
authors: V
authors: V
authors: Heinemann
authors: M P
authors: MP
authors: Ebert
authors: R P
authors: RP
authors: Laubender
authors: P
authors: P
authors: Bevan
authors: C
authors: C
authors: Mala
authors: S
authors: S
authors: Boeck
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001798:Blood Proteins / Q000008:administration & dosage*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010091:Oximes; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D010879:Piperazines / Q000008:administration & dosage*; D013449:Sulfonamides / Q000008:administration & dosage*; D000093542:Gemcitabine
chemical_list: D001798:Blood Proteins; D010091:Oximes; D010879:Piperazines; D013449:Sulfonamides; C031220:urokinase inhibitor; D003841:Deoxycytidine; C580590:upamostat; D000093542:Gemcitabine