Use of high doses of the methotrexate in children suffering from some form of cancer: specificities of the accompanying therapy, assessing the toxicity

Materials and methods. During the period from October 2015 to February 2018, a patient cohort (n = 26) who received high-dose MTX therapy with the following nosology: osteosarcoma – 4, hemoblastosis – 11, and CNS – 11 tumors was evaluated. The average age of the patients was 7.3 years old; ratio of boys:girls – 2.25: 1. The used doses were ranged from 1 to 12 g/m², the doses schedules ranged from 4 to 36 hours; the total number of courses during the observation period was 94; the average number of courses per patient was 3. In all cases, the level of MTX in the blood serum was monitored with correction of the dose of leucovorin according to international recommendations. Estimated toxicity parameters were the following: allergic reactions, skin and mucous membrane damage, neurologic disorders, myelosuppression, hepatic transaminase and creatinine growth.

Results. Transitory toxicity was noted for 100 % of patients, of which clinically significant was in 62.7 % of cases. The development of complications that had required the use of antibacterial and blood transfusion therapy occurred after 36 courses of therapy (38.2 %), of wich in 24 cases (66.6 %) MTX was performed in combination with other antitumor agents. No cases of acute kidney injury were presented, there was no significant difference in creatinine level before and after high-dose MTX courses. The highest frequency of episodes of hepatotoxicity was noted in the group of patients diagnosed with “osteosarcoma”. After reduction the episodes of toxicity with the use of high-dose MTX, all patients continued programmed chemotherapy.

Conclusions. Against the background of an adequate accompanying therapy (infusion therapy with alkalization of urine, pharmacodynamic monitoring, correction of the leucovorin dose), it is possible to achieve satisfactory tolerability of high doses of MTX. The combination of high doses of MTX with other antitumor drugs leads to a significant increase in the toxicity. Despite of the noted complications of therapy, continuation of treatment with the use of previous doses of MTX (does not require reduction) is possible, and a decrease in the rate of MTX removal is not always a predictor of episodes of the toxicity.