title: Phase II study of gemcitabine in combination with regional arterial infusion of nafamostat mesilate for advanced pancreatic cancer.
abstract: OBJECTIVE
  To evaluate the efficacy of regional arterial infusion of the synthetic serine protease inhibitor nafamostat mesilate combined with gemcitabine for the treatment of patients with unresectable locally advanced or metastatic pancreatic cancer.
  
  
  METHODS
  A single-arm, single center, institutional review board-approved phase II trial was conducted. Thirty-five of 38 consecutive patients were included in the study. Patients received nafamostat mesilate (4.8 mg/kg continuous regional arterial infusion) with gemcitabine (1000 mg/m intravenously) on days 1, 8, and 15. This treatment was repeated at 28-day intervals. The primary endpoints were to evaluate overall survival and 1-year survival rate. The secondary endpoints were to assess therapeutic response and clinical benefit response. Overall survival times were estimated by the Kaplan-Meier survival analysis.
  
  
  RESULTS
  The median survival time was 10.0 months, and the 1-year survival rate was 40.0%. The response rate and disease control rate were 17.1% and 88.6%, respectively. A fraction of 25% of the patients who required opioids for cancer-related pain could reduce their opioid intake, and 37.1% of the patients showed healthy weight gain. Among the patients with metastatic pancreatic cancer, the median survival time was 9.0 months, and the 1-year survival rate was 32.0%. The proposed regimen offers an economic advantage compared with recent therapy regimens that have shown significant improvements in median survival over standard chemotherapy with gemcitabine.
  
  
  CONCLUSIONS
  An alternative regimen for unresectable pancreatic cancer, especially for metastatic pancreatic cancer, is proposed based on acceptable survival time, clinical benefit, and cost advantage.
authors.affiliation: Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan. uwatadashi@msn.com
authors.forename: Tadashi
authors.initials: T
authors.lastname: Uwagawa
authors.forename: Takeyuki
authors.initials: T
authors.lastname: Misawa
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Tsutsui
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Ito
authors.forename: Takeshi
authors.initials: T
authors.lastname: Gocho
authors.forename: Shoichi
authors.initials: S
authors.lastname: Hirohara
authors.forename: Shunichi
authors.initials: S
authors.lastname: Sadaoka
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Yanaga
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001550:Benzamidines; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D006146:Guanidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007261:Infusions, Intra-Arterial; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D001550:Benzamidines; D006146:Guanidines; D003841:Deoxycytidine; C032855:nafamostat; D000093542:Gemcitabine