Preliminary Findings on the Use of Targeted Therapy in Combination with Sodium Phenylbutyrate in Recurrent Advanced Pancreatic Cancer—A Potential Strategy for Improved Survival scirp.org/journal/PaperInformation.aspx?PaperID=50936&utm_campaign=facebook&utm_medium=zyf Metastatic pancreatic cancer carries an estimated five-year survival rate of only 2%. Gemcitabine-based chemotherapy remains a first-line standard-of-care treatment for elderly patients with advanced pancreatic cancer. Combination chemotherapy FOLFIRINOX offers better results, but it is not recommended for the older patient population due to substantial toxicity. Standard-of-care second-line treatment is not yet established and is used in approximately 30% of patients since performance status is too low to consider further therapy. Targeted therapies with a single agent and in combinations have been tested in numerous clinical trials, but except for the combination of gemcitabine and erlotinib, have not yet proven efficacy. Here, we present preliminary findings of improved overall survival (OS) using a combination of sodium phenylbutyrate with various chemotherapeutic and targeted agents in stage IV A and B pancreatic cancer patients who failed at least one line of chemotherapy. The results suggest a strategy of simultaneous interruption of signal transmission involving multiple pathways in the second-line treatment that are believed to interfere with cell cycle, cancer cell metabolism, autophagy and maintenance of cancer stem cells and promote apoptosis. In this group of patients, median OS was higher compared to other second-line therapies (10.5 months compared to between 2.9 and 6.5 months in other studies, and in the best supportive care group, 2.3 months). Given the understanding that our findings are preliminary, we propose the validation of our initial results using a well-designed Phase I/II trial in recurrent advanced pancreatic cancer.
Posted on: Thu, 30 Oct 2014 06:49:40 +0000
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