IngentaConnect Cyclophosphamide-methotrexate `metronomic' chemotherapy for the p...

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.

Keywords: metastatic breast cancer; metronomic chemotherapy; cyclophosphamide; methotrexate; pharmacoeconomics; cost-effectiveness ratio; sensitivity analysis

Document Type: Research article

DOI: 10.1093/annonc/mdi240

Affiliations: 1: Division of Pharmacology and Chemotherapy, Department of Oncology, Transplants and Advanced Technologies, University of Pisa, Via Roma, Pisa, Italy; 2: Molecular and Cellular Biology Research, Sunnybrook and Women's College Health Sciences Centre, Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; 3: Senior consultant of SAS®, Pisa; 4: U.O. Oncologia Medica, Ospedale Civile, Livorno, Italy

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Cyclophosphamide-methotrexate ‘metronomic’ chemotherapy for the palliative treatment of metastatic breast cancer. A comparative pharmacoeconomic evaluation