RT info:eu-repo/semantics/article
T1 Highly efficacious nontoxic preclinical treatment for advanced metastatic breast cancer using combination oral UFT-cyclophosphamide metronomic chemotherapy
A1 Muñoz Martínez, Raquel
A1 Man, Shan
A1 Shaked, Yuval
A1 Lee, Christina R.
A1 Wong, John
A1 Francia, Giulio
A1 Kerbel, Robert S.
K1 Breast cancer
K1 Cáncer de mama
K1 Chemotherapy
K1 Quimioterapia
K1 Uracil-tegafur
K1 Tegafur-uracilo
K1 Cyclophosphamide
K1 Ciclofosfamida
AB Metronomic antiangiogenic chemotherapy, the prolongedadministration of relatively low drug doses, at close regularintervals with no significant breaks, has been mainly studiedat the preclinical level using single chemotherapeutic drugs,frequently in combination with a targeted antiangiogenicdrug, and almost always evaluated on primary localizedtumors. We tested a ‘‘doublet’’ combination metronomicchemotherapy treatment using two oral drugs, UFT, a5-fluorouracil (5-FU) prodrug administered by gavage, andcyclophosphamide, for efficacy and toxicity in a new mousemodel of advanced, terminal, metastatic human breast cancer.The optimal biological dose of each drug was first determinedby effects on levels of circulating endothelial progenitor cellsas a surrogate marker for angiogenesis, which was assessed tobe 15 mg/kg for UFT and 20 mg/kg for cyclophosphamide. Acombination treatment was then evaluated in mice withadvanced 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 verymodest survival advantages whereas a combination of the tworesulted in a remarkable prolongation of survival, with noevidence of overt toxicity despite 140 days of continuoustherapy, such that a significant proportion of mice survivedfor over a year. In contrast, this striking therapeutic effect ofthe combination treatment was not observed when tested onprimary orthotopic tumors. We conclude that combinationoral low-dose daily metronomic chemotherapy, using cyclophosphamide and UFT, is superior to monotherapy and seemsto be a safe and highly effective experimental antimetastatictherapy, in this case, for advanced metastatic breast cancer
PB American Association for Cancer Research
SN 1538-7445
YR 2006
FD 2006
LK http://uvadoc.uva.es/handle/10324/41000
UL http://uvadoc.uva.es/handle/10324/41000
LA eng
NO Cancer Research, 2006, vol. 66, n. 7. p. 3386-3391
NO Producción Científica
DS UVaDOC
RD 02-dic-2024