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Comparison of high-dose methotrexate (HDMTX) toxicity in elderly and younger
patients (pts) with primary central nervous system lymphoma (PCNSL)
K. Jahnke, A. Korfel, P. Martus, M. Weller, U. Herrlinger,
L. Fischer, E. Thiel
Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany;
University of Tübingen, Tübingen, Germany
Background. A reduced dose of HDMTX is often given to elderly pts because
of the risk of toxicity.
This may result in loss of treatment efficacy and
further prognosis impairment in this poor prognosis population.
Methods. HDMTX toxicity was prospectively evaluated in an ongoing
randomized multicenter phase IV study in PCNSL pts.
In 154 pts, an analysis of
toxicity according to the pts´ age was performed.
Median age was 61 years
(yrs).
Sixty-five pts were < 60 yrs and had a median Karnofsky
performance score (KPS) of 80, 89 pts were > 60 yrs and had a median KPS of
70.
HDMTX (4 g/m² per course) was administered as a 4-hour intravenous (IV)
infusion on day 1 every 2 weeks for a maximum of 6 courses and was accompanied
by IV hydration, urinary alkalinization, and leucovorin rescue at a dose of 30
mg IV every 6 hours after 24 hours of HDMTX infusion.
HDMTX dose reduction was
performed according to creatinine clearance values evaluated before each
treatment course: the percentage of dose reduction equaled the percentage of
creatinine clearance value below 100 ml/min.
Results. Toxicity was generally mild to moderate.
No statistically
significant differences in frequency and severity of toxicity between pts <
60 and > 60 yrs were noted (table).
No therapy-related deaths occurred.
Dose
reduction due to decrease in creatinine clearance was much more frequent in pts
> 60 yrs than in those < 60 yrs (43.9 % versus 17.5 %, p =
0.001).
Conclusions. HDMTX is safe regardless of age when dose reduction is
performed according to creatinine clearance.
Dose reduction solely according to
age does not appear to be justified.
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Toxicity
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Toxicity grade (World Health Organization)
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No. of pts < 60 yrs (%)
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No. of pts > 60 yrs (%)
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p-value (Fisher´s Exact Test)
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Hemoglobin
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0-2
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58 (89.2)
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76 (85.4)
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0.629
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3-4
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7 (10.8)
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13 (14.6)
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Leukocytes
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0-2
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60 (92.3)
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76 (85.4)
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0.214
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3-4
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5 (7.7)
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13 (14.6)
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Thrombocytes
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0-2
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62 (95.4)
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79 (88.8)
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0.240
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3-4
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3 (4.6)
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10 (11.2)
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Infections
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0-2
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56 (86.2)
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77 (86.5)
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1.0
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3-4
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9 (13.8)
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12 (13.5)
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Nephrotoxicity
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0-2
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64 (98.5)
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83 (93.3)
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0.240
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3-4
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1 (1.5)
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6 (6.7)
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Mucositis
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0-2
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64 (98.5)
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83 (95.4)
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0.393
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Copyright 2004 American Society of Clinical Oncology All rights
reserved worldwide.
Source: http://www.asco.org/ac/1,1003,_12-002636-00_18-0026-00_19-001459,00.asp
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