Implication of clinical and paraclinical covariates in the pharmacokinetics of high dose MTX (HD-MTX) in patients with osteosarcoma

12022 Background: Methotrexate (MTX) is a mainstay in the treatment of ostosarcoma. MTX is characterized by a narrow therapeutic window, combined with high intra- and inter-patient variabilities. In our institute, safe administration of high dose MTX is ensured by using bayesian, adaptive dosing with feedback strategy. In patients with osteosarcoma, up to 20g/patient MTX is administred following an 8h infusion. From the 6th hour, the dose is tailored according to individual pharmacokinetics parameters, determined in real-time from two early sampling times (T3.5, T4.5) and a reference population. This method enables accurate adjustment of most patients around a target Cend of 10−3 M/L. Still, 15–20% of the patients show reduced MTX elimination rate, thus leading to an overlasting hospitalization time with folate rescue required to prevent severe toxicities. In this work, we studied the relevance of clinical or pareaclinical covariates likely to be associated with the MTX clearance so as to identify patient...