4CPS-280 Benefits of pharmacokinetic estimation of methotrexate levels in paediatric osteosarcoma patients

Background and importance Monitoring of methotrexate serum levels in osteosarcoma paediatric patients includes estimation of serum levels of methotrexate 24 hours after initiation of the infusion ([MTX24h]), which allows folinic acid rescue to be started at adjusted doses. When pharmacokinetic estimation is not possible, the standard rescue (15 mg/m2/6 hours) is recommended and subsequently adjusted according to the real [MTX24h]. Aim and objectives To evaluate the correlation and concordance of the estimated and real [MTX24h], and the benefits of the estimation in comparison with the dosage by protocol. Material and methods A retrospective study of paediatric patients treated with 12 g/m2 methotrexate monitored by the pharmacy department from January 2014 to June 2020 was conducted. Estimated [MTX24h] was determined with a Bayesian model with PKS software. Variables collected were age, sex, number of cycles received, estimated and real [MTX24h] and folinic rescue dose. Pearson and intraclass correlation coefficients between real and estimated [MTX24h] were calculated. The agreement between the dosage of folinic acid by protocol and by estimating [MTX24h] was assessed with the Cohen kappa coefficient. Results 23 patients, 56.5% (13) men, median age 14 (4–17) years, received 152 cycles of methotrexate. The median number of cycles per patients was 8 (2–8). Median estimated [MTX24h] was 7 (2–80) and real [MTX24h] was 8 (1–85). The Pearson’s correlation coefficient and intraclass correlation coefficient for real and estimated [MTX24h] were r=0.949 and CCI=0.974, respectively, indicating a high linear correlation and concordance between the two. In 71.8% (94) of the cycles, the estimated folinic rescue matched with the dose which the patient should receive according to real [MTX24h]. Assuming the dosing of folinic acid at 24 hours by protocol (15 mg/m2/6 hours) in all cases, only 35.1% (46) of patients would have received the correct dose. The Cohen kappa between the two methods was 0.189, indicating only slight agreement between both methods in favour of estimating [MTX24h]. Conclusion and relevance Estimated and real [MTX24h] showed high correlation and concordance, and in most cases the folinic acid rescue dose was correctly administered based on the estimated [MTX24h]. These results seem to indicate that the estimation of [MTX24h] and posterior estimation of folinic acid rescue are superior to systematic administration of 15 mg/m2/6 hours. References and/or acknowledgements Conflict of interest No conflict of interest