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High-dose methotrexate for elderly patients with primary CNS lymphoma

Departments of Neurology, Hematology, and Oncology, Tufts-New England Medical Center, Boston, MA (J.-J.Z.); Departments of Neurology (E.R.G., M.M.M., W.N., K.N., F.H.H., T.T.B.) and Radiation Oncology (T.T.B.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; Department of Biostatistics, Harvard School of Public Health and Biostatistics Center, Massachusetts General Hospital, Boston, MA (D.A.E., R.A.B.); USA

Address correspondence to Tracy Batchelor, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Yawkey 9E, Massachusetts General Hospital, 55 Fruit St., Boston, MA 02114, USA (tbatchelor{at}partners.org).

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 70 years (median, 74 years) who were treated with high-dose MTX (3.5–8 g/m²) 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.

Key Words: chemotherapy • elderly • high-dose methotrexate • primary CNS lymphoma

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