Comprehensive evaluation of high dose methotrexate therapy: a retrospective observational trial

Methotrexate (MTX) is a commonly prescribed drug with both chemotherapeutic and immunosuppressive applications. However, when administered in high doses (HDMTX ≥ 500 mg/m²), it can lead to serious side effects, particularly nephrotoxicity and hepatotoxicity. Although 48-h MTX levels monitoring is fundamental for the evaluation of the risk of these toxicities, the relationship between MTX level and the actual clinical outcomes is not yet fully addressed. This study aims to evaluate the predictors of 48-h serum MTX levels and the toxicity profile associated with patients receiving HDMTX for management of cancer, with a particular focus on nephrotoxicity, hepatotoxicity, length of hospital stay (LOS), antimicrobial use, and 30-day mortality.

A retrospective cohort study was conducted at the National Cancer Institute, Cairo University. Patients receiving HDMTX as part of their cancer treatment in the period from January 2022 to December 2024 were included. Data collection included patient demographics, administered MTX doses, 48-h serum MTX levels, medical and medication history, antimicrobials used, and recorded adverse effects. The outcome of the study encompassed the identification of predictors for 48-h MTX levels and their association with acute kidney injury (AKI), ICU admission, and LOS. In addition to the associations with hepatotoxicity, antimicrobial usage, and mortality. Statistical analysis was performed using SPSS version 26.0.

Among 143 patients, elevated 48-h MTX levels (≥ 1.28 μmol/L) were associated with pleural effusion (P-value 0.038), patients diagnosed with lymphoma (P-value 0.05), and increased antimicrobial use (P-value < 0.05). A significant association was found between HDMTX and the use of carbapenems, vancomycin and fluoroquinolones (P-value < 0.05). Non-significant relation was found between HDMTX and AKI as well as LOS. Hepatotoxicity was significantly more common in patients with osteosarcoma rather than hematological malignancies, while LOS was shorter in osteosarcoma cases compared to hematological malignancies.

The serum levels of 48-h MTX are vital metrics of toxicity, as they determine the duration of hospitalization, the number of antimicrobials used, and the mortality rate. Thus, it is crucial to monitor these levels to reduce the complications associated with HDMTX usage.