title: Metronomic low-dose oral cyclophosphamide and methotrexate plus or minus thalidomide in metastatic breast cancer: antitumor activity and biological effects.
abstract: BACKGROUND
  We previously demonstrated efficacy and impact on serum vascular endothelial growth factor (VEGF) for metronomic cyclophosphamide (C) and methotrexate (M) in patients with breast cancer. New metronomic schedules were investigated.
  
  
  METHODS
  Patients with advanced breast cancer were randomized to receive oral C (50 mg daily) and M (2.5 mg twice daily on days 1 and 4) (arm A) or the same regimen plus thalidomide (200 mg daily) (arm B).
  
  
  RESULTS
  The mean VEGF level decreased from 378.9 (+/-274.4) pg/ml at baseline to 305.9 (+/-203.6) pg/ml at 2 months (P<0.001), with similar change with respect to baseline in both arms. In 171 evaluable patients we observed three complete remissions (CR) in both arms A and B, 15 partial remission (PR) in arm A and seven in arm B, for an overall response of 20.9% [95% confidence interval (CI) 12.9% to 31%] in arm A and 11.8% (95% CI 5.8% to 20.6%) in arm B. The clinical benefit (CR+PR+SD>or=24 weeks) was 41.5% for both arms. Toxicity was generally mild. Higher neurological toxicity (2% versus 60%; P<0.0001) and constipation (8% versus 51%; P<0.0001) was observed in arm B.
  
  
  CONCLUSIONS
  Metronomic low-dose CM induced a drop in VEGF, and was effective and minimally toxic. The addition of thalidomide did not improve results.
authors.affiliation: Division of Medical Oncology, University of Milan School of Medicine, European Institute of Oncology, Milan, Italy. marco.colleoni@ieo.it
authors.forename: M
authors.initials: M
authors.lastname: Colleoni
authors.forename: L
authors.initials: L
authors.lastname: Orlando
authors.forename: G
authors.initials: G
authors.lastname: Sanna
authors.forename: A
authors.initials: A
authors.lastname: Rocca
authors.forename: P
authors.initials: P
authors.lastname: Maisonneuve
authors.forename: G
authors.initials: G
authors.lastname: Peruzzotti
authors.forename: R
authors.initials: R
authors.lastname: Ghisini
authors.forename: M T
authors.initials: MT
authors.lastname: Sandri
authors.forename: L
authors.initials: L
authors.lastname: Zorzino
authors.forename: F
authors.initials: F
authors.lastname: Nolè
authors.forename: G
authors.initials: G
authors.lastname: Viale
authors.forename: A
authors.initials: A
authors.lastname: Goldhirsch
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009362:Neoplasm Metastasis; D013792:Thalidomide / Q000008:administration & dosage; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D020533:Angiogenesis Inhibitors; D000964:Antimetabolites, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D013792:Thalidomide; D003520:Cyclophosphamide; D008727:Methotrexate