title: Cyclophosphamide-methotrexate 'metronomic' chemotherapy for the palliative treatment of metastatic breast cancer. A comparative pharmacoeconomic evaluation.
abstract: BACKGROUND
  Metronomic chemotherapy-the chronic administration of chemotherapy at relatively low, minimally toxic doses on a frequent schedule of administration at close regular intervals, with no prolonged drug-free breaks-is a potentially novel approach to the control of advanced cancer disease. It is thought to work primarily through antiangiogenic mechanisms and has, as an advantage, the property of significantly reducing undesirable toxic side-effects. The aim of the present study was to evaluate the cost effectiveness of cyclophosphamide-methotrexate 'metronomic' chemotherapy in the palliative treatment of pretreated metastatic breast cancer.
  
  
  METHODS
  Low-dose cyclophosphamide-methotrexate 'metronomic' chemotherapy was compared with outcome and resource utilisation data of published phase II trials regarding metastatic breast cancer, performed in western countries, mostly in Europe. All direct costs associated with metastatic breast cancer treatment were included and adjusted to year 2003 values. Sensitivity analyses were performed and variations to the values of key parameters were assessed.
  
  
  RESULTS
  Low-dose cyclophosphamide-methotrexate 'metronomic' therapy was assessed to be a cost-effective/cost-saving therapy for palliative treatment for metastatic breast cancer when compared with novel chemotherapy strategies (phase II trials). Compared with the 11 phase II mono- and combination chemotherapies, metronomic treatment showed marked cost savings in each case and improved cost effectiveness. Sensitivity analyses showed the results were robust to variations to the values of key parameters with very few exceptions.
  
  
  CONCLUSIONS
  Metronomic cyclophosphamide-methotrexate is significantly cost effective. If validated by prospective randomized trials, the treatment concept could reduce healthcare costs, especially those associated with the combined use of new, highly expensive, molecularly targeted therapies.
authors.affiliation: Division of Pharmacology and Chemotherapy, Department of Oncology, Transplants and Advanced Technologies, University of Pisa, Via Roma, Pisa, Italy. g.bocci@med.unipi.it
authors.forename: G
authors.initials: G
authors.lastname: Bocci
authors.forename: M
authors.initials: M
authors.lastname: Tuccori
authors.forename: U
authors.initials: U
authors.lastname: Emmenegger
authors.forename: V
authors.initials: V
authors.lastname: Liguori
authors.forename: A
authors.initials: A
authors.lastname: Falcone
authors.forename: R S
authors.initials: RS
authors.lastname: Kerbel
authors.forename: M
authors.initials: M
authors.lastname: Del Tacca
mesh_terms: D000284:Administration, Oral; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000191:economics*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000191:economics* / Q000556:secondary; D017322:Clinical Trials, Phase II as Topic; D003362:Cost-Benefit Analysis; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000191:economics; D016527:Drug Costs; D017850:Economics, Pharmaceutical; D006801:Humans; D007262:Infusions, Intravenous; D008727:Methotrexate / Q000008:administration & dosage / Q000191:economics; D010166:Palliative Care
chemical_list: D003520:Cyclophosphamide; D008727:Methotrexate