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Treatment of Primary CNS Lymphoma With Methotrexate and Deferred Radiotherapy: A Report of NABTT 96–07

Tracy Batchelor, Kathryn Carson, Alison O’Neill, Stuart A. Grossman, Jane Alavi, Pamela New, Fred Hochberg, Regina Priet

From the Massachusetts General Hospital, Boston, MA; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; University of Alabama at Birmingham, Birmingham, AL; University of Pennsylvania, Philadelphia, PA; University of Texas at San Antonio, San Antonio, TX.

Address reprint requests to Tracy Batchelor, MD, MPH, c/o The NABTT CNS Consortium, Cancer Research Building, Room G87, 1650 Orleans St, Baltimore, MD 21231; email: jfisher{at}jhmi.edu.

Purpose: A multicenter, phase II study of single-agent, intravenous methotrexate in newly diagnosed non-AIDS-related primary CNS lymphoma was conducted in the New Approaches to Brain Tumor Therapy (NABTT) CNS Consortium.

Methods: Methotrexate (8 g/m²) was initially administered every 2 weeks. The primary end point was radiographic CR or PR, as defined by standard radiographic criteria, and secondary end points were survival and drug-related toxicity.

Results: Twenty-five patients were enrolled with a mean age of 60 years and median Karnofsky Performance Score of 80. Three of 14 patients who underwent lumbar puncture had malignant cells on CSF cytopathology, and five of 25 patients had ocular involvement. Two patients could not be evaluated for the primary end point because of the absence of measurable disease in one and death before radiologic imaging in another. All patients have completed the treatment program or progressed. Among 23 patients, there were 12 CR (52%), five PR (22%), one (4%) with stable disease, and five progressions (22%) while on therapy. Seven patients died of tumor progression, and two died of other causes. Median progression-free survival was 12.8 months. Median overall survival for the entire group had not been reached at 22.8+ months. The toxicity of this regimen was modest, with no grade 3 or 4 toxicity in 13 of 25 patients, grade 3 toxicity in eight of 25 patients, and grade 4 toxicity in four of 25 patients after 287 cycles of chemotherapy.

Conclusion: These results indicate that high-dose methotrexate is associated with modest toxicity and a radiographic response proportion (74%) comparable to more toxic regimens.

Supported by National Cancer Institute Cancer Therapy Evaluation Program Grant CA 62475.

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