[Therapeutic drug monitoring of methotrexate after its administration in high-dose protocols]

Abstract

After HD-MTX infusions, i.e. at a dose>1 g/m2, monitoring of serum MTX concentrations is a standard practice which helps reducing the incidence of toxicity in patients with decreased clearance by guiding dose adjustment of leucovorin. Therapeutic monitoring of methotrexate is based on iterative measurements of serum concentration until concentration is below a certain threshold. This practice is supported by numerous observations of exposure-related toxicity as well as some clinical studies comparing drug exposure between patients with and without toxicity. Despite no prospective clinical study has clearly demonstrated the usefulness of methotrexate TDM, historical comparison reveals a huge reduction of toxicity-related events over past decades. Systematic monitoring may also help identifying patients with abnormally high methotrexate concentrations, who require immediate treatment with carboxypeptidase.