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


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/m(2) HDMTX followed by leucovorin rescue.


RESULTS
Toxicity was generally mild with toxicities of WHO grade > or =3 usually <10%. The differences in the incidence and severity of toxicity were not statistically significant between patients >60 years and < or =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 < or =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.
Jahnke
K
K
Department of Hematology, Oncology and Transfusion Medicine, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany. kristoph.jahnke@charite.de
Korfel
A
A
Martus
P
P
Weller
M
M
Herrlinger
U
U
Schmittel
A
A
Fischer
L
L
Thiel
E
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008875:Middle Aged; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate