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The role of methotrexate in combination with doxorubicin and cisplatin in preoperative chemotherapy of bone sarcomas is still a topic of discussion. Many studies have shown a correlation between peak serum methotrexate levels, tumor response to chemotherapy, and treatment outcome. It is possible that the negative results of the effectiveness of methotrexate were compromised due to the maintenance of insufficient doses or an incorrect regimen of drug administration. The optimal mode of administration of methotrexate has not been established. However, the control group in the EURAMOS-1 study of the American Osteosarcoma Research Group (AOST) is considered as the standard. Major eligibility criteria are histologically confirmed diagnosis of osteosarcoma and age from 24 to 40 years. Since it is believed that the elimination of methotrexate in older patients is more delayed than in patients under 24 years of age, and can lead to serious adverse events (AE). However, the use of modern standard methods of hemodialysis makes it possible to avoid such AE in the case of the first signs of their occurrence. The technology of convection mass transfer is associated with the inevitable loss of certain protein fractions of the patient's plasma. At present, dialyzers have been developed that are highly permeable to water, electrolytes and medium molecular substances, characterized by an ultrafiltration coefficient of >20 ml/hour/mm Hg, designated as high-flux, preserving the most important protein fractions in the blood and effectively eliminating those appearing in blood flow during chemotherapy xenobiotics with a higher molecular weight. Trial started January 2022. Current enrollment status: 3 of planned 25 patients have been enrolled. Peak concentrations of methotrexate were reached without the need for hemodialysis. The planned number of patients is justified by the needs of statistical analysis: 25 patients are planned to be included in trial with 90% evidence-based effectiveness with an acceptable margin of error of 5% and efficiency in the comparative group of 70%, and in the trial group of 100% (from 70 to 100%). NCT05057130. The authors. Has not received any funding.
Tararykova et al. (Fri,) studied this question.