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Annals of Oncology Advance Access originally published online on January 14, 2005
Annals of Oncology 2005 16(3):445-449; doi:10.1093/annonc/mdi075
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© 2005 European Society for Medical Oncology

High-dose methotrexate toxicity in elderly patients with primary central nervous system lymphoma

K. Jahnke1,*, A. Korfel1, P. Martus2, M. Weller3, U. Herrlinger3, A. Schmittel1, L. Fischer1 and E. Thiel1 On behalf of the German Primary Central Nervous System Lymphoma Study Group (G-PCNSL-SG)

Departments of 1 Hematology, Oncology and Transfusion Medicine, and 2 Medical Informatics, Biometry and Epidemiology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin; 3 Department of General Neurology, Center for Neurology, University of Tübingen, Tübingen, Germany

* Correspondence to: Dr K. Jahnke, Department of Hematology, Oncology and Transfusion Medicine, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany. Tel: +49-30-8445-2337; Fax: +49-30-8445-4468; Email: kristoph.jahnke{at}charite.de

Background: The dose of high-dose methotrexate (HDMTX) in elderly patients often has to be reduced, resulting in a loss of treatment efficacy. We evaluated HDMTX-related toxicity with special regard to age distribution in patients with primary central nervous system lymphoma (PCNSL) in a phase IV multicenter trial.

Patients and methods: One hundred and fifty-four patients (median age 61 years; 89 patients >60 years old, 21 patients >70 years old) received 619 HDMTX cycles. Toxicity was evaluated prospectively using the WHO classification. Unless a reduced dose was required after calculating a decreased glomerular filtration rate (GFR), the patients received 4 g/m2 HDMTX followed by leucovorin rescue.

Results: Toxicity was generally mild with toxicities of WHO grade ≥3 usually <10%. The differences in the incidence and severity of toxicity were not statistically significant between patients >60 years and ≤60 years old. The same was true for therapy termination owing to MTX toxicity and for delayed serum MTX clearance. Dose reduction significantly differed between patients ≤60 years and those >60 years old (18% versus 44%; P=0.001).

Conclusions: HDMTX is a safe treatment for PCNSL patients regardless of age, with adherence to dose reduction determined by calculating the GFR before each treatment cycle.

Key words: elderly, glomerular filtration rate, methotrexate, toxicity


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