Hadeer Ehab Barakat, Kholood Ashraf El Bahy, Sandy Victor Labib, Yasser Zakaria Aldesouky, Abdelrahman Ayman Ismail, Mohamed El Sayed Mohamed, Febrona Louis Sedky, Asmaa Mohamed Abdelhady, Dalia Hamdy Gaballah, Doha Ashraf Ali, Passant Mohamed Refaat, Hasnaa Al Sayed Mohamed, Ahmed Zayed Mohamed, Salwa Selim Ibrahim, Ayman M Noreddin, Abdel-Moneim M Osman, Esraa M Abdelkeriem, Mohamed M Sayed-Ahmed, Riham M Karkeet
{"title":"Comprehensive evaluation of high dose methotrexate therapy: a retrospective observational trial.","authors":"Hadeer Ehab Barakat, Kholood Ashraf El Bahy, Sandy Victor Labib, Yasser Zakaria Aldesouky, Abdelrahman Ayman Ismail, Mohamed El Sayed Mohamed, Febrona Louis Sedky, Asmaa Mohamed Abdelhady, Dalia Hamdy Gaballah, Doha Ashraf Ali, Passant Mohamed Refaat, Hasnaa Al Sayed Mohamed, Ahmed Zayed Mohamed, Salwa Selim Ibrahim, Ayman M Noreddin, Abdel-Moneim M Osman, Esraa M Abdelkeriem, Mohamed M Sayed-Ahmed, Riham M Karkeet","doi":"10.1186/s43046-025-00324-9","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Methotrexate (MTX) is a commonly prescribed drug with both chemotherapeutic and immunosuppressive applications. However, when administered in high doses (HDMTX ≥ 500 mg/m<sup>2</sup>), 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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":17301,"journal":{"name":"Journal of the Egyptian National Cancer Institute","volume":"37 1","pages":"69"},"PeriodicalIF":1.8000,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the Egyptian National Cancer Institute","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1186/s43046-025-00324-9","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
期刊介绍：
As the official publication of the National Cancer Institute, Cairo University, the Journal of the Egyptian National Cancer Institute (JENCI) is an open access peer-reviewed journal that publishes on the latest innovations in oncology and thereby, providing academics and clinicians a leading research platform. JENCI welcomes submissions pertaining to all fields of basic, applied and clinical cancer research. Main topics of interest include: local and systemic anticancer therapy (with specific interest on applied cancer research from developing countries); experimental oncology; early cancer detection; randomized trials (including negatives ones); and key emerging fields of personalized medicine, such as molecular pathology, bioinformatics, and biotechnologies.
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