title: Therapeutic efficacy of metronomic chemotherapy with cyclophosphamide and doxorubicin on murine mammary adenocarcinomas.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Experimental Genetics, School of Medical Sciences, National University of Rosario, Rosario, Argentina.
authors.forename: L E
authors.initials: LE
authors.lastname: Mainetti
authors.forename: M J
authors.initials: MJ
authors.lastname: Rico
authors.forename: M V
authors.initials: MV
authors.lastname: Fernández-Zenobi
authors.forename: H A
authors.initials: HA
authors.lastname: Perroud
authors.forename: E A
authors.initials: EA
authors.lastname: Roggero
authors.forename: V R
authors.initials: VR
authors.lastname: Rozados
authors.forename: O G
authors.initials: OG
authors.lastname: Scharovsky
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D059250:Administration, Metronomic; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D019394:Ki-67 Antigen / Q000378:metabolism; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D013534:Survival; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D000903:Antibiotics, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D019394:Ki-67 Antigen; C498355:Mki67 protein, mouse; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D004317:Doxorubicin; D003520:Cyclophosphamide
keywords: angiogenesis; cyclophosphamide; doxorubicin; mammary adenocarcinomas; metronomic chemotherapy; toxic effect