High dose methotrexate for elderly patients with primary central nervous system lymphoma

¹ Department of Neuro-Oncology, Massachusetts General Hospital, 55 Fruit Street, Yawkey 9E, Boston, MA, 02114
² Departments of Neurology and Hematology and Oncology, Tufts-New England Medical Center, Boston, MA
³ Department of Biostatistics, Harvard School of Public Health and Biostatistics Center, Massachusetts General Hospital, Boston, MA, USA
⁴ Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
⁵ Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA

^* To whom correspondence should be addressed. E-mail: egerstner{at}partners.org.

	Abstract

Purpose: The introduction of methotrexate-based chemotherapy has improved median survival for patients with primary central nervous system lymphoma (PCNSL). Older age is a negative prognostic marker in patients with PCNSL and may increase the likelihood of methotrexate toxicity. We studied the response and adverse effects of intravenous high-dose methotrexate in patients who were 70 at the time of diagnosis. Patients and Methods: We identified 31 patients at our institution diagnosed with PCNSL at age 70 who were treated with high-dose methotrexate (3.5 gm/m2-8 gm/m2) as initial therapy from 1992-2006. The best response to methotrexate was determined by contrast enhanced MRI. Toxicity was analyzed by chart review. Results: Thirty-one patients with a median age of 74 received a total of 303 cycles of methotrexate. Overall, 87.9% of the cycles required dose reduction because of impaired creatinine clearance. The median number of cycles per patient was 8. 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. Grades I-IV toxicities were observed in 27/31 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). Conclusions: High-dose methotrexate is associated with a high proportion of radiographic responses and a low proportion of grades III/IV toxicity in patients 70. High-dose methotrexate should be considered as a feasible treatment option in elderly patients with PCNSL.

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

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