(P 158) NEOADJUVANT COMBINATION OF DOXORUBICIN, CISPLATIN AND METHOTREXATE IN PATIENTS AGED 24-40 YEARS WITH OSTEOSARCOMA UNDER THE COVERAGE OF HEMODIALYSIS. AMAP2021-7-2. ONGOING TRIAL

Objective: Ongoing trial. The role of methotrexate in combination with doxorubicin and cispatin 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. The main practical problem in the use of triple chemotherapy in patients aged 24 years and older is that the slow clearance of methotrexate can delay the introduction of the next cycle of doxorubicin-cisplatin, thereby reducing the dose intensity and negatively affecting the result.

Methods: Ongoing trial. Major eligibility criteria are histologically confirmed diagnosis of osteosarcoma and age from 24 to 40 years. The advantage of the three-component chemotherapy in increase of the therapeutic pathomorphosis degree and increase the frequency of tumor response to treatment, which consider will further to improve the disease prognosis. Currently, the use of such a regimen in patients over 24 years of age is a controversial and controversial recommendation. 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.

Results: Ongoing trial. Trial started january 2022. Current enrollment status: 1 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%)

Conclusion: Ongoing trial. Despite the current standard of preoperative polychemotherapy for high-grade bone sarcomas, the problem of tumor sensitization remains open. Since the administration of triple preoperative chemotherapy in patients under 24 years of age has shown its effectiveness, there is currently a tendency to expand these indications for patients aged 24 to 40 years, and the use of hemodialysis can potentially reduce the risk of developing AEs. Clinical trial information: NCT05057130