The prognostic value of serum methotrexate area under curve in elderly primary CNS lymphoma patients

Kasenda, Benjamin and Rehberg, Marcel and Thürmann, Petra and Franzem, Melanie and Veelken, Hendrik and Fritsch, Kristina and Schorb, Elisabeth and Finke, Jürgen and Lebiedz, Dirk and Illerhaus, Gerald. (2012) The prognostic value of serum methotrexate area under curve in elderly primary CNS lymphoma patients. Annals of Hematology, 91 (8). pp. 1257-1264.

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Official URL: http://edoc.unibas.ch/53528/

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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 [AUC(dn), 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.
Faculties and Departments:03 Faculty of Medicine > Departement Klinische Forschung > Clinical Epidemiology and Biostatistics CEB > Klinische Epidemiologie (Bucher H)
UniBasel Contributors:Kasenda, Benjamin
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Springer Verlag
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:09 Oct 2017 08:59
Deposited On:09 Oct 2017 08:59

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