Abstract
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.
Highlights
The American Cancer Society (ACS Cancer Statistics 2014) estimates that 39,590 patients will die from the pancreatic cancer and the number of new cases in the United States will increase to 46,420 [1]
Subjects were diagnosed with metastatic or locally advanced pancreatic ductal adenocarcinoma (PDA), and after recurrence received their treatment in private practice at Burzynski Clinic (BC) in Houston, TX
The data are not sufficient to draw definite conclusions, but the results suggest that a successful treatment combination could consist of PB, erlotinib, pazopanib, or sorafenib in combination with a mammalian target of rapamycin inhibitor, SRC inhibitor or human epidermal growth factor receptor 2 (HER-2) inhibitor for patients with amplification of Targeted Drugs Daily Dose/Duration Sorafenib Sirolimus Everolimus Vorinostat
Summary
The American Cancer Society (ACS Cancer Statistics 2014) estimates that 39,590 patients will die from the pancreatic cancer and the number of new cases in the United States will increase to 46,420 [1]. For patients with metastatic pancreatic cancer, the five-year survival rate is only 2% and is surpassed only by glioblastoma multiforme (GBM) [3]-[5]. A number of phase II and III trials in advanced pancreatic cancer have been conducted, but significant improvement in survival has not been demonstrated, except for FOLFIRINOX and a combination of nab-paclitaxel with gemcitabine [7]-[27]. Despite these discouraging statistics, there is optimism with the rapid development of molecular targeted approaches for the treatment of this almost uniformly deadly disease [28] [29]
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