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Annals of Oncology Advance Access published online on January 14, 2005
Annals of Oncology, doi:10.1093/annonc/mdi075
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© 2005 European Society for Medical Oncology
Received July 20, 2004
Revised September 28, 2004
Accepted September 29, 2004

Original article

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

K. Jahnke 1*, A. Korfel 1, P. Martus 2, M. Weller 3, U. Herrlinger 3, A. Schmittel 1, L. Fischer 1, E. Thiel 1, and On behalf of the German Primary Central Nervous System Lymphoma Study Group (G-PCNSL-SG)

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

* To whom correspondence should be addressed.
K. Jahnke, E-mail: kristoph.jahnke{at}charite.de


  Abstract

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.

Keywords: elderly; glomerular filtration rate; methotrexate; toxicity.
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