Neoadjuvant Combination of Doxorubicin, Cisplatin and Methotrexate in Patients Aged 24-40 Years With Primary Bone Tumors

Overview

Two cycles of neoadjuvant three-component chemotherapy according to the MAP prototoc: Doxorubicin 25 mg / m2 IV on days 1-3, Cisplatin 120 mg / m2 IV on day 1 against the background of hyperhydration. G-CSF support from 4 to 13 days. Methotrexate 12 g / m2 at 28 and 35 days IV with leucovorin 60 mg / m2 in the first 5 days after each administration of methotrexate. The interval between cycles is 42 days. The advantage of this regimen is to use the three-component chemotherapy regimen, which should increase the degree of tumor necrosis and increase the rate of tumor response to treatment, which will further improve the disease prognosis. Currently, the use of such treatment for adult patients (over 24 years old) is controversial. Since it is believed that the elimination of methotrexate in adult patients is more delayed than in patients under 24 years old, and can lead to serious adverse events (SAE). However, the use of modern standard methods of hemodialysis makes it possible to avoid SAE.

The role of methotrexate in neoadjuvant chemotherapy for bone tumors is a topic for debate. However, the benefits of methotrexate have been confirmed in at least one phase II study showing better results with high doses of methotrexate in the context of triple chemotherapy. Moreover, many studies have shown a correlation between peak serum methotrexate levels, tumor response to chemotherapy, and treatment outcome. Thus, it is possible that the negative results of the effectiveness of methotrexate have been compromised due to the administration of insufficient doses or incorrect administration of the drug. The optimal regimen of methotrexate administration 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 with the use of triple chemotherapy in a group of patients aged 24 and older is that the slow clearance of methotrexate can delay the administration of the next cycle of doxorubicin-cisplatin, thereby reducing the dose intensity and adversely affecting the outcome. Currently, there are both isolated clinical cases and observations of a small number of included patients. The use of three-component neoadjuvant chemotherapy for primary bone tumors will improve the rate of response to treatment, reduce the frequency of recurenses and disease progression.