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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.

AbstractBACKGROUND:
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.
CONCLUSION:
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.
AuthorsV Heinemann, M P Ebert, R P Laubender, P Bevan, C Mala, S Boeck
JournalBritish journal of cancer (Br J Cancer) Vol. 108 Issue 4 Pg. 766-70 (Mar 5 2013) ISSN: 1532-1827 [Electronic] England
PMID23412098 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial)
Chemical References
  • Blood Proteins
  • Piperazines
  • Sulfonamides
  • upamostat
  • urokinase inhibitor
  • Deoxycytidine
  • gemcitabine
Topics
  • Adenocarcinoma (drug therapy)
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
  • Blood Proteins (administration & dosage)
  • Deoxycytidine (administration & dosage, analogs & derivatives)
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pancreatic Neoplasms (drug therapy)
  • Piperazines (administration & dosage)
  • Sulfonamides (administration & dosage)

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