2024-03-28T14:52:11Zhttps://uvadoc.uva.es/oai/requestoai:uvadoc.uva.es:10324/410002021-06-23T09:52:38Zcom_10324_1134com_10324_931com_10324_894col_10324_1213
Highly efficacious nontoxic preclinical treatment for advanced metastatic breast cancer using combination oral UFT-cyclophosphamide metronomic chemotherapy
Muñoz Martínez, Raquel
Man, Shan
Shaked, Yuval
Lee, Christina R.
Wong, John
Francia, Giulio
Kerbel, Robert S.
Producción Científica
Metronomic antiangiogenic chemotherapy, the prolonged
administration of relatively low drug doses, at close regular
intervals with no significant breaks, has been mainly studied
at the preclinical level using single chemotherapeutic drugs,
frequently in combination with a targeted antiangiogenic
drug, and almost always evaluated on primary localized
tumors. We tested a ‘‘doublet’’ combination metronomic
chemotherapy treatment using two oral drugs, UFT, a
5-fluorouracil (5-FU) prodrug administered by gavage, and
cyclophosphamide, for efficacy and toxicity in a new mouse
model of advanced, terminal, metastatic human breast cancer.
The optimal biological dose of each drug was first determined
by effects on levels of circulating endothelial progenitor cells
as a surrogate marker for angiogenesis, which was assessed to
be 15 mg/kg for UFT and 20 mg/kg for cyclophosphamide. A
combination treatment was then evaluated in mice with
advanced metastatic disease using a serially selected metastatic variant of the MDA-MB-231 breast cancer-cell line, 231/
LM2-4. UFT or cyclophosphamide treatment showed only very
modest survival advantages whereas a combination of the two
resulted in a remarkable prolongation of survival, with no
evidence of overt toxicity despite 140 days of continuous
therapy, such that a significant proportion of mice survived
for over a year. In contrast, this striking therapeutic effect of
the combination treatment was not observed when tested on
primary orthotopic tumors. We conclude that combination
oral low-dose daily metronomic chemotherapy, using cyclophosphamide and UFT, is superior to monotherapy and seems
to be a safe and highly effective experimental antimetastatic
therapy, in this case, for advanced metastatic breast cancer
2020-06-05T12:50:37Z
2020-06-05T12:50:37Z
2006
info:eu-repo/semantics/article
Cancer Research, 2006, vol. 66, n. 7. p. 3386-3391
1538-7445
http://uvadoc.uva.es/handle/10324/41000
10.1158/0008-5472.CAN-05-4411
eng
https://cancerres.aacrjournals.org/content/66/7/3386
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/3.0/
© 2006 American Association for Cancer Research
Attribution-NonCommercial-NoDerivs 3.0 Unported
American Association for Cancer Research
SI