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Statistical examination to determine whether only 48-h value for serum concentration during high-dose methotrexate therapy is a predictor for clinical adverse events using ordered logistic regression analysis

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Abstract

Sustained elevation of serum methotrexate (MTX) concentrations (>1.0 μM) for 48 h (48-h value) has been found to have predictive significance for the development of toxicity. However, we sometimes experience severe adverse events during high-dose (HD) MTX therapy even if serum MTX concentrations comply with recommended values. We performed a retrospective study to identify predictors for occurrence of adverse events and examined whether only the 48-h value is a statistically significant predictor for clinical adverse events during HD MTX therapy. The subjects were 32 hematological patients (n = 58 episodes) treated with MTX at Kyoto Prefectural University of Medicine between February 2003 and July 2007. Ordered logistic regression analysis was used to identify predictors for occurrence of adverse events. The predictive factors identified were: 24-h continuous infusion therapy (24-h C-IV) (long infusion time) [odds ratio (OR) = 2.890, confidence interval (CI) =1.493–5.594; P = 0.0016] for fatigue, higher dose [OR = 2.282, CI = 1.287–4.046; P = 0.0048] and combination chemotherapy [OR = 2.177, CI = 1.059–4.477; P = 0.0344] for stomatitis, and 24-h C-IV [OR = 2.573, CI = 1.101–6.016; P = 0.0291] for neutropenia. We found that only the 48-h value was not a predictor for clinical adverse events for HD MTX therapy. A major limitation of the present study was the small number of participants. However, our findings suggest that there is evidence that a long infusion time is a significant predictor for general fatigue and neutropenia, while a higher dose and combination chemotherapy are predictors for stomatitis.

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Authors and Affiliations

  1. Department of Hospital Pharmacy,, Kyoto Prefectural University of Medicine, Kawaramachi Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan

    Yuko Kanbayashi

  2. Pharmainformatics and Pharmacometrics, Graduate School of Pharmaceutical Sciences,, Osaka University, Suita, Japan

    Yuko Kanbayashi, Kousuke Okamoto & Tatsuya Takagi

  3. Department of Hematology and Oncology,, Iwate Medical University, Morioka, Japan

    Kenichi Nomura

  4. Genome Information Research Center, Research Institute for Microbial Diseases,, Osaka University, Suita, Japan

    Tatsuya Takagi

  5. Research Collaboration Center on Emerging and Re-emerging Infections, Suita, Japan

    Tatsuya Takagi

  6. Department of Hematology and Oncology,, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan

    Yosuke Matsumoto, Shigeo Horiike & Masafumi Taniwaki

  7. Department of Clinical Molecular Genetics and Laboratory Medicine,, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan

    Masafumi Taniwaki

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  1. Yuko Kanbayashi
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  2. Kenichi Nomura
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  3. Kousuke Okamoto
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  4. Yosuke Matsumoto
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  7. Masafumi Taniwaki
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Correspondence to Yuko Kanbayashi.

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Kanbayashi, Y., Nomura, K., Okamoto, K. et al. Statistical examination to determine whether only 48-h value for serum concentration during high-dose methotrexate therapy is a predictor for clinical adverse events using ordered logistic regression analysis. Ann Hematol 89, 965–969 (2010). https://doi.org/10.1007/s00277-010-0965-6

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  • DOI: https://doi.org/10.1007/s00277-010-0965-6

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