Background: The current standard of care for pancreatic cancer is weekly gemcitabine administered for 3 of 4 weeks with a 1-week break between treatment cycles. Maximum tolerated dose (MTD)-driven regimens as such are often associated with toxicities. Recent studies demonstrated that frequent dosing of chemotherapeutic drugs at relatively lower doses in metronomic regimens also confers anti-tumour activity but with fewer side effects. Methods: Herein, we evaluated the anti-tumour efficacy of metronomic vs MTD gemcitabine, and investigated their effects on the tumour microenvironment in two human pancreatic cancer xenografts established from two different patients. Results: Metronomic and MTD gemcitabine significantly reduced tumour volume in both xenografts. However, K trans values were higher in metronomic gemcitabine-treated tumours than in their MTD-treated counterparts, suggesting better tissue perfusion in the former. These data were further supported by tumour-mapping studies showing prominent decreases in hypoxia after metronomic gemcitabine treatment. Metronomic gemcitabine also significantly increased apoptosis in cancer-associated fibroblasts and induced greater reductions in the tumour levels of multiple pro-angiogenic factors, including EGF, IL-1$\alpha$, IL-8, ICAM-1, and VCAM-1. Conclusion: Metronomic dosing of gemcitabine is active in pancreatic cancer and is accompanied by pronounced changes in the tumour microenvironment.
%0 Journal Article
%1 Cham2010
%A Cham, K K Y
%A Baker, J H E
%A Takhar, K S
%A Flexman, J A
%A Wong, M Q
%A Owen, D A
%A Yung, A
%A Kozlowski, P
%A Reinsberg, Stefan A
%A Chu, E M
%A Chang, C-W A
%A Buczkowski, A K
%A Chung, S W
%A Scudamore, C H
%A Minchinton, A I
%A Yapp, D T T
%A Ng, S S W
%D 2010
%I Nature Publishing Group
%J Br. J. Cancer
%K angiogenesis,gemcitabine,metronomic anti cancer,tumour chemotherapy,pancreatic microenvironment myown
%N 1
%P 52--60
%T Metronomic gemcitabine suppresses tumour growth, improves perfusion, and reduces hypoxia in human pancreatic ductal adenocarcinoma.
%U http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2905290&tool=pmcentrez&rendertype=abstract
%V 103
%X Background: The current standard of care for pancreatic cancer is weekly gemcitabine administered for 3 of 4 weeks with a 1-week break between treatment cycles. Maximum tolerated dose (MTD)-driven regimens as such are often associated with toxicities. Recent studies demonstrated that frequent dosing of chemotherapeutic drugs at relatively lower doses in metronomic regimens also confers anti-tumour activity but with fewer side effects. Methods: Herein, we evaluated the anti-tumour efficacy of metronomic vs MTD gemcitabine, and investigated their effects on the tumour microenvironment in two human pancreatic cancer xenografts established from two different patients. Results: Metronomic and MTD gemcitabine significantly reduced tumour volume in both xenografts. However, K trans values were higher in metronomic gemcitabine-treated tumours than in their MTD-treated counterparts, suggesting better tissue perfusion in the former. These data were further supported by tumour-mapping studies showing prominent decreases in hypoxia after metronomic gemcitabine treatment. Metronomic gemcitabine also significantly increased apoptosis in cancer-associated fibroblasts and induced greater reductions in the tumour levels of multiple pro-angiogenic factors, including EGF, IL-1$\alpha$, IL-8, ICAM-1, and VCAM-1. Conclusion: Metronomic dosing of gemcitabine is active in pancreatic cancer and is accompanied by pronounced changes in the tumour microenvironment.
@article{Cham2010,
abstract = {Background: The current standard of care for pancreatic cancer is weekly gemcitabine administered for 3 of 4 weeks with a 1-week break between treatment cycles. Maximum tolerated dose (MTD)-driven regimens as such are often associated with toxicities. Recent studies demonstrated that frequent dosing of chemotherapeutic drugs at relatively lower doses in metronomic regimens also confers anti-tumour activity but with fewer side effects. Methods: Herein, we evaluated the anti-tumour efficacy of metronomic vs MTD gemcitabine, and investigated their effects on the tumour microenvironment in two human pancreatic cancer xenografts established from two different patients. Results: Metronomic and MTD gemcitabine significantly reduced tumour volume in both xenografts. However, K trans values were higher in metronomic gemcitabine-treated tumours than in their MTD-treated counterparts, suggesting better tissue perfusion in the former. These data were further supported by tumour-mapping studies showing prominent decreases in hypoxia after metronomic gemcitabine treatment. Metronomic gemcitabine also significantly increased apoptosis in cancer-associated fibroblasts and induced greater reductions in the tumour levels of multiple pro-angiogenic factors, including EGF, IL-1$\alpha$, IL-8, ICAM-1, and VCAM-1. Conclusion: Metronomic dosing of gemcitabine is active in pancreatic cancer and is accompanied by pronounced changes in the tumour microenvironment.},
added-at = {2018-10-29T06:43:31.000+0100},
author = {Cham, K K Y and Baker, J H E and Takhar, K S and Flexman, J A and Wong, M Q and Owen, D A and Yung, A and Kozlowski, P and Reinsberg, Stefan A and Chu, E M and Chang, C-W A and Buczkowski, A K and Chung, S W and Scudamore, C H and Minchinton, A I and Yapp, D T T and Ng, S S W},
biburl = {https://www.bibsonomy.org/bibtex/23fcf961333519156b324b62ed6007e33/drsar},
institution = {Department of Advanced Therapeutics, British Columbia Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 1L3.},
interhash = {1c92366f7b6c89a92bc2d5f303b24433},
intrahash = {3fcf961333519156b324b62ed6007e33},
journal = {Br. J. Cancer},
keywords = {angiogenesis,gemcitabine,metronomic anti cancer,tumour chemotherapy,pancreatic microenvironment myown},
number = 1,
pages = {52--60},
publisher = {Nature Publishing Group},
timestamp = {2018-10-29T07:15:10.000+0100},
title = {{Metronomic gemcitabine suppresses tumour growth, improves perfusion, and reduces hypoxia in human pancreatic ductal adenocarcinoma.}},
url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2905290{\&}tool=pmcentrez{\&}rendertype=abstract},
volume = 103,
year = 2010
}