Abstract 3023
Background
It has been reported that bacteria can metabolize gemcitabine (gem) into its inactive and contribute to the drug resistance. It was also reported that the resistance was abrogated by cotreatment with antibiotics [Geller LT, et al. Science 2017], in which, many of human pancreatic ductal adenocarcinoma samples contained causal bacteria which potentially mediates tumor resistance to gem. We therefore hypothesized the use of antibiotics may affect clinical outcomes of gem therapy in patients (pts) with pancreatic cancer (PC).
Methods
We retrospectively investigated pts with advanced PC who were treated with gem alone as first-line treatment in our single institute between 2009 and 2017. The association of use of antibiotics before gem treatment with progression-free survival (PFS) and overall survival (OS) was analyzed using Cox proportional hazards model and log-rank test.
Results
One hundred twenty-four pts were treated with gem alone as first-line therapy and had the following characteristics: median age of 72yrs, 59% male, 39%/54%/4%/3% for PS0/1/2/3, 53%/26%/19% for primary tumor of head/body/tail, median PFS of 3.4 months, and median OS of 7.7 months. In 124 pts, 59% used antibiotics before treatment with gem. One hundred pts discontinued due to disease progression, while 24 pts due to toxicity or pts’ wish. Pts who received antibiotics had significantly longer PFS than pts who did not receive antibiotics (4.2 vs. 2.1 months, HR 0.64, 95%CI 0.43-0.96, P = 0.029). The association was not statistically significant after multivariate analysis adjusted for PS, tumor location, and number of metastatic sites (HR 0.73, 95%CI 0.45-1.17, P = 0.19). Median OS was numerically longer in pts with use of antibiotics than in pts without antibiotics (8.0 vs. 5.5 months).
Conclusions
Our study indicated that antibiotic use before gem therapy was associated with favorable outcome in pts with advanced PC treated with gem. These findings warrant further exploratory studies and suggest scientific approach to identify antibiotics as an enhancer for gem.
Clinical trial identification
Legal entity responsible for the study
Takako Eguchi Nakajima.
Funding
Has not received any funding.
Editorial Acknowledgement
Disclosure
Y. Sunakawa: Honoraria: Taiho Pharmaceutical, Chugai Pharma, Yakult Honsha, Takeda, Merck Serono, Bayer Yakuhin, Eli Lilly Japan, Sanofi. N. Izawa: Honoraria: Taiho Pharmaceutical Co., Ltd., Merck Serono Co., Ltd. T.E. Nakajima: Personal financial interests: Eli Lilly, Sanofi, Chugai, Sawai, Bayer, Bristol, Taiho, Merck, Ono, Takeda, Mochida, MSD; Institutional financial interests: Ono, Taiho, A2 Health Care, JCRO, Daiichi-Sankyo, Mediscience Planning. All other authors have declared no conflicts of interest.
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