TITLE:
Preliminary Findings on the Use of Targeted Therapy in Combination with Sodium Phenylbutyrate in Recurrent Advanced Pancreatic Cancer—A Potential Strategy for Improved Survival
AUTHORS:
Stanislaw R. Burzynski, Tomasz J. Janicki, Gregory S. Burzynski, Sheldon Brookman
KEYWORDS:
Pancreatic Cancer, Pancreatic Cancer Survival, Personalized Targeted Therapy, Sodium Phenylbutyrate
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.5 No.12,
October
28,
2014
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.