Phase II multicenter study of brief single-agent methotrexate followed by irradiation in primary CNS lymphoma

Purpose: To assess, in a multi-institutional setting, the impact on relapse , survival, and toxicity of adding two cycles of intravenous methotrexate t o cranial irradiation for immunocompetent patients with primary CNS lymphom a. Patients and Methods: Forty-six patients with a median age of 58 years and Eastern Cooperative Oncology Group performance status 0 to 3 were entered o nto this phase II study. The protocol consisted of methotrexate 1 g/m(2) on days 1 and 8 followed by cranial irradiation on day 15. A whole-brain dose of 45 Gy was followed by a boost of 5.4 Gy. Intrathecal chemotherapy and s pinal irradiation were given only to patients for whom cytologic examinatio n of CSF was positive for CNS lymphoma. The median follow-up time wets 36 m onths, with a minimum potential follow-up of 12 months. Results: Median survival was 33 months, with 2-year probability of survival 62% +/- 15% (95% confidence interval). Twenty patients have relapsed. The predominant site of relapse was the brain. Neither performance status nor a ge was found to influence survival. Six patients developed a dementing illn ess at a median of 16 months after treatment, and three of these died as a consequence. Conclusion: A brief course of intravenous methotrexate before cranial irrad iation is associated with 2-year and median survival rates superior to thos e reported for radiotherapy alone and similar to more intensive combined-mo dality regimens. Neurotoxicity remains an important competing risk for thes e patients. J Clin Oncol 18:519-526. (C) 2000 by American Society of Clinic al Oncology.