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Ann Oncol ; 24(9): 2310-6, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23666914

ABSTRACT

BACKGROUND: Metronomic chemotherapy (MCT) refers to the chronic and equally spaced administration of low doses of different chemotherapy drugs, without extended rest periods. Herein, we investigated the therapeutic efficacy of metronomic cyclophosphamide (Cy) combined with doxorubicin (Dox) in two mouse mammary adenocarcinoma models. MATERIALS AND METHODS: Mice were s.c. challenged with M-234p or M-406 mammary tumors, and when the tumors reached ∼150 mm(3), they were treated with: (I) no treatment (controls); (II) Cy in the drinking water (30 mg/kg body weight/day); (III) Dox (0.5 mg/kg body weight i.p. three times/week); (IV) treated as (II) + (III). Mice challenged i.v. with M-234p or M-406 tumor cells received, on day 3, the same treatments. RESULTS: We found that MCT with Cy plus Dox inhibited tumor growth, decreased lung metastases, and increased the median survival time, while having low toxic effect. Combined MCT was more effective than each monotherapy causing decrease in VEGF serum concentration and tumor proliferation rate plus increase in tumor apoptosis. CONCLUSION(S): The therapeutic benefits of combined MCT with Cy and Dox on mammary adenocarcinomas together with its low toxic effect profile suggest the possibility of future translation into the clinic.


Subject(s)
Adenocarcinoma/drug therapy , Administration, Metronomic , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Mammary Neoplasms, Animal/drug therapy , Animals , Antibiotics, Antineoplastic/administration & dosage , Antibiotics, Antineoplastic/therapeutic use , Antineoplastic Agents, Alkylating/administration & dosage , Antineoplastic Agents, Alkylating/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Apoptosis/drug effects , Cell Proliferation/drug effects , Cyclophosphamide/therapeutic use , Disease Models, Animal , Doxorubicin/therapeutic use , Female , Ki-67 Antigen/metabolism , Lung Neoplasms/prevention & control , Lung Neoplasms/secondary , Mice , Mice, Inbred BALB C , Neoplasm Metastasis/prevention & control , Neovascularization, Pathologic/drug therapy , Survival , Vascular Endothelial Growth Factor A/blood
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