Schwarz MA
Tanzania
Research Article
Increasing Bioavailability of Cytotoxic Agents through Prolonged Therapy and Addition of Polymechanistic Antiangiogenic Agents Enhances Antitumor Response in Pancreatic Cancer
Author(s): Awasthi N, Schwarz MA, Wang C, Williams SN and Schwarz REAwasthi N, Schwarz MA, Wang C, Williams SN and Schwarz RE
Pancreatic ductal adenocarcinoma (PDAC) has a very poor prognosis. Meaningful therapeutic options for unresectable PDAC remain limited and therefore more efficient therapeutic strategies are urgently required. We explored the approach of manipulating dose intensity of cytotoxic agents through prolonged therapy and by combination with antiangiogenic agents in experimental PDAC. Median animal survival over controls (19 days) was increased after prolonged therapy (up to 6 weeks) with gemcitabine to 29 days (a 53% increase, p = 0.008). Addition of two antiangiogenic agents, bevacizumab and EMAP, further extended median survival to 46 days (a 142% increase, p = 0.0001). Corresponding survival extension after therapy with similar agents limited to 2 weeks was 37% for gemcitabine and 127% after gemcitabine plus antiangiogenic agents. Pharmacokinetic analysis revealed that the addition of ant.. View More»
