Combination Therapy of Capecitabine with Cyclophosphamide as a Second-Line Treatment after Failure of Paclitaxel
plus Bevacizumab Treatment in a Human Triple Negative Breast Cancer Xenograft Model
1240
colorectal cancer xenograft models [7], PTX has been
reported to increase the level of TP in xenografted tu-
mors [16] and, therefore,, the TP level in tumor would be
increased by PTX + BEV treatment in the 1st-line treat-
ment in our study. However, because antitumor activity
gradually receded during the 1st-line treatment, the amount
of TP induced by PTX might also decrease, if the anti-
tumor activity was attenuated by PTX resistance. To cla-
rify the above hypothesis, the change over time in tumor
TP levels in 1st-line treatment should be examined. In the
2nd-line treatment, CAPE + CPA combination showed an
extremely high antitumor activity compared to CAPE or
CPA monotherapy. Because the TP level in tumor was
upregulated by CPA treatment, the superior antitumor
effect of CAPE + CPA combination compared to CAPE
monotherapy may be attributed to the increased 5-FU
level in tumor tissue caused by facilitated conversion
from CAPE by TP. These results are similar to that in the
1st-line therapy reported previously [15].
Our preclinical results suggest that the CAPE + CPA
combination therapy may be effective as a 2nd-line ther-
apy for progressive disease after PTX + BEV 1st-line
treatment in TNBC patients.
5. Acknowledgements
We thank Dr. Kazushige Mori for helpful discussion and
comments regarding the manuscript.
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