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Journal of Clinical Oncology, Vol 20, Issue 24 (December), 2002: 4643-4648
© 2002 American Society for Clinical Oncology

Combination Chemotherapy and Radiotherapy for Primary Central Nervous System Lymphoma: Radiation Therapy Oncology Group Study 93-10

By Lisa M. DeAngelis, Wendy Seiferheld, S. Clifford Schold, Barbara Fisher, Christopher J. Schultz

From the Memorial Sloan-Kettering Cancer Center, New York, NY; American College of Radiology, Philadelphia, and University of Pittsburgh, Pittsburgh, PA; Medical College of Wisconsin, Milwaukee, WI; and University of Western Ontario, London, Ontario, Canada.

Address reprint requests to Lisa M. DeAngelis, MD, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021; email: deangell{at}mskcc.org

PURPOSE: Primary CNS lymphoma (PCNSL) is an aggressive primary brain tumor. Cranial irradiation alone rarely results in long-term disease control or prolonged survival. We prospectively studied the use of combination chemotherapy plus cranial irradiation in newly diagnosed patients with PCNSL.

PATIENTS AND METHODS: We enrolled 102 newly diagnosed, immunocompetent patients with PCNSL; 98 were assessable. Patients first received five cycles of methotrexate 2.5 g/m2, vincristine, procarbazine, and intraventricular methotrexate (12 mg). Whole-brain radiotherapy (RT) was administered to a total dose of 45 Gy and all patients received high-dose cytarabine after RT.

RESULTS: Fifty-eight percent of patients with measurable disease had a complete response to preirradiation chemotherapy and 36% had a partial (> 50%) response, for a 94% response rate. Median progression-free survival was 24.0 months and overall survival was 36.9 months. Age was an important prognostic factor; median survival was 50.4 months in patients younger than 60 and only 21.8 months in those aged 60 or older (P < .001). Fifty-three percent of patients had grade 3 or 4 toxicity during induction chemotherapy, half of which was hematologic. However, 12 patients (15%) experienced severe delayed neurologic toxicity, eight of whom died.

CONCLUSION: This is the first multicenter trial demonstrating improved survival with the combination of chemotherapy plus RT compared with previous reports of RT alone. A high-dose methotrexate-based regimen produced a high response rate before RT was administered. High-dose methotrexate combined with cranial irradiation is an effective therapeutic approach to PCNSL, but neurotoxicity is a delayed risk of this approach.

Presented in part at the Thirty-Fifth Annual Meeting of the American Society of Clinical Oncology, Atlanta, GA, May 15-18, 1999.


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