INDIVIDUAL DOSAGE ADJUSTMENT OF HIGH-DOSE METHOTREXATE IN CLINICAL-PRACTICE

Since its discovery in 1948 the clinical applications of methotrexate have widened; and in order to overcome resistances to methotrexate, th e concept of high-dose methotrexate has been proposed. The use of resc ue by folinic acid, as well as rapid dosage of MTX coupled with pharma cokinetic studies, have permitted Its to administer an optimum dose of drug, with maximum therapeutic effects, but with reduced toxicity. In dividual adaptation of posology, calculated using the test dose or acc ording to population pharmacokinetic with a Bayesian method of paramet er estimation (which allows Its to adjust tile dose of high-dose metho trexate during its infusion) permits control of inter and intra-indivi dual variations of this drug. After analysis of the different methods proposed, we now present the results of 778 courses of treatment by hi gh-dose methotrexate (while separating 238 courses for osteosarcoma as these formed a homogenous group of patients). Theoretical maximum con centration and length of infusion were decided by physicians, followed by individual adaptation of posology by pharmacologists at the sixth hour of infusion of methotrexate. This treatment unites maximum securi ty for the patient with no serious side effects (no grade 4 toxicity a ccording to WHO classification), while receiving an optimum dose of me thotrexate. In courses of MTX for osteosarcoma, the dose of MTX can be further intensified without risk, by administering on aver age 65% mo re than the usual dose in adults (8 g/m(2)) and 10% more than the usua l dose in children (12 g/m(2)).