title: High-dose methotrexate for elderly patients with primary CNS lymphoma.
abstract: The introduction of methotrexate (MTX)-based chemotherapy has improved median survival for patients with primary CNS lymphoma (PCNSL). Older age is a negative prognostic marker in patients with PCNSL and may increase the likelihood of MTX toxicity. We studied the response and adverse effects of intravenous high-dose MTX in patients who were 70 or more years of age at the time of diagnosis. We identified 31 patients at our institution diagnosed with PCNSL at age > or =70 years (median, 74 years) who were treated with high-dose MTX (3.5-8 g/m(2)) as initial therapy from 1992 through 2006. The best response to MTX was determined by contrast-enhanced MRI. Toxicity was analyzed by chart review. These 31 patients received a total of 303 cycles of MTX (median, eight cycles per patient). Overall, 87.9% of the cycles required dose reduction because of impaired creatinine clearance. In 30 evaluable patients, the overall radiographic response rate was 96.7%, with 18 complete responses (60%) and 11 partial responses (36.7%). Progression-free survival and overall survival were 7.1 months and 37 months, respectively. Grade I-IV toxicities were observed in 27 of 31 patients and included gastrointestinal disturbances in 58% (3.2% grade III), hematological complications in 80.6% (6.5% grade III), and renal toxicity in 29% (0% grade III/IV). High-dose MTX is associated with a high proportion of radiographic responses and a low proportion of grade III/IV toxicity in patients 70 or more years of age. High-dose MTX should be considered as a feasible treatment option in elderly patients with PCNSL.
authors.affiliation: Department of Neurology, Tufts-New England Medical Center, Boston, MA, USA.
authors.forename: Jay-Jiguang
authors.initials: JJ
authors.lastname: Zhu
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Gerstner
authors.forename: David A
authors.initials: DA
authors.lastname: Engler
authors.forename: Maciej M
authors.initials: MM
authors.lastname: Mrugala
authors.forename: Whitney
authors.initials: W
authors.lastname: Nugent
authors.forename: Kristin
authors.initials: K
authors.lastname: Nierenberg
authors.forename: Fred H
authors.initials: FH
authors.lastname: Hochberg
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Betensky
authors.forename: Tracy T
authors.initials: TT
authors.lastname: Batchelor