Abstract

Background: Metronomics is defined by the combination of metronomic chemotherapy and drug repositioning. Since off-patent chemotherapeutic drugs can be used and given the low toxicity profile of this approach, metronomics appears to be an invaluable alternative to bring affordable targeted therapies in low-income countries. Objective: The aim of this study was to report on the preliminary efficacy and safety of a metronomic vincristine/cyclophosphamide/methotrexate/valproic acid regimen given to children with refractory cancer of various tumor types or with a very advanced disease. Materials and Methods: This prospective, single-center study evaluated the use of a metronomics protocol, consisting of a first cycle of weekly vincristine 1.5 mg/m 2 (days: 1, 8, 15 and 22), daily cyclophosphamide 25 mg/m 2 (days: 1-21), twice weekly methotrexate 15 mg/m² (days: 21-42) and daily valproic acid (30 mg/kg/d) followed by a 1-week break. For the following cycles, vincristine was administrated only at week 1 and 5 of the cycle. This treatment was proposed to children with refractory disease and patients who were not eligible for the protocols available in the hospital. Adverse events were determined through laboratory analyses and investigator observations. Results: From January 2010 to January 2011, 7 children (mean age: 5.4 ± 3 years old) were treated. Most frequent diagnosis was retinoblastoma. Two partial responses were observed in patients with neuroblastoma and retinoblastoma. These two patients are alive with stable disease at last follow-up (6 and 26 months, respectively) after stopping treatment. Conclusion: Metronomics allows treating patients with advanced or refractory or relapsing disease and the introduction of targeted treatments in low-income countries. The potential of metronomics in children and young adults living in middle- and low-income countries warrants further larger studies.

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