Abstract
Studies on pharmacokinetics and pharmacodynamics of high-dose methotrexate chemotherapy (HD-MTX) in elderly primary central nervous system lymphoma (PCNSL) patients are rare. MTX exposure time has recently been proposed as an outcome determining factor in PCNSL. We investigated 49 immunocompetent PCNSL patients (female N = 30, male N = 19, median age 73 years) who were treated according to HD-MTX-based protocols. A two-compartment pharmacokinetic model was used to describe the MTX clearance. Response to treatment was assessed by MRI. We used multivariable models to investigate the association between MTX exposure and tumor response as well as survival. Dose normalized MTX peak serum levels [C max, μmol/L g] and dose normalized area under the curve [AUCdn, μmol h/L g] were higher in females than in males, respectively [59.4 (f) vs. 48.1 (m), P < 0.001; 373.2 (f) vs. 271.9 (m), P = 0.008]. Increasing AUC was inversely correlated with tumor response. AUC values above 2,126 h μmol/L were independently associated with shorter overall and progression-free survival [hazard ratio (HR), 4.56, 95 % CI 1.74–11.94; HR 2.87, 95 % CI 1.18–7.00]. Exceedingly high MTX AUC levels can have a negative impact on progression-free and overall survivals in elderly PCNSL patients.
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Acknowledgments
We would also like to thank Vanessa Haug and Stefan Haug for their help and support in collecting the data. Special thanks to Juliane Schäfer and Hartmut Henss for fruitful discussions and valuable input to the manuscript.
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The study was not supported by any external funding source.
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The authors declare no conflict of interest.
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Kasenda, B., Rehberg, M., Thürmann, P. et al. The prognostic value of serum methotrexate area under curve in elderly primary CNS lymphoma patients. Ann Hematol 91, 1257–1264 (2012). https://doi.org/10.1007/s00277-012-1441-2
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DOI: https://doi.org/10.1007/s00277-012-1441-2