Phase II Study of Gemcitabine in Combination With Regional Arterial Infusion of Nafamostat Mesilate for Advanced Pancreatic Cancer

Abstract

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. 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. 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. An alternative regimen for unresectable pancreatic cancer, especially for metastatic pancreatic cancer, is proposed based on acceptable survival time, clinical benefit, and cost advantage.