The Use of Chemotherapy Plus Radiotherapy Plus Azidothymidine in Patients With AIDS-Related Lymph Node Cancer

To determine the safety and toxicity of high-dose systemic methotrexate (MTX) and dexamethasone (DEX) combined with zidovudine (AZT) and brain irradiation in patients with AIDS-related primary central nervous system (CNS) lymphoma and to determine response rates and survival of treated patients. Also to determine if the treatment inhibits HIV replication in patients who are HIV culture and/or antigen positive and to assess the incidence of opportunistic infection in these patients Results of radiation given to patients with AIDS-related high-grade CNS lymphoma have been disappointing, with short survival times due to infection complications. However, complete response has been documented after radiation in some patients. High-dose MTX will be used to improve the possibility of a greater antineoplastic response than that obtained by radiation alone. Since the underlying immunodeficiency state is not affected by therapy directed against the lymphoma, patients are still prone to life-threatening opportunistic infections or relapse of lymphomatous disease within the CNS. Accordingly, AZT will also be used in an attempt to alter the overall natural history of the disease. Results of radiation given to patients with AIDS-related high-grade CNS lymphoma have been disappointing, with short survival times due to infection complications. However, complete response has been documented after radiation in some patients. High-dose MTX will be used to improve the possibility of a greater antineoplastic response than that obtained by radiation alone. Since the underlying immunodeficiency state is not affected by therapy directed against the lymphoma, patients are still prone to life-threatening opportunistic infections or relapse of lymphomatous disease within the CNS. Accordingly, AZT will also be used in an attempt to alter the overall natural history of the disease. Radiation begins on day 1 of therapy. Patients receive dexamethasone orally (PO) or by intravenous injection (IV) on days 1-10. MTX IV over 6 hours weekly for a total of 4 doses starts 1 week after completion of the cranial radiation. Leucovorin (LCV) IV or PO begins 6 hours after MTX has been completed over 6 hours for 8 doses. AZT while awake starts on day 1 of therapy and continues for 52 weeks. Patients are reevaluated with computerized tomography (CT) or magnetic resonance imaging (MRI) scan of the brain at conclusion of radiation therapy and systemic treatment, 6 and 10 weeks respectively. If there is a complete or partial response (CR or PR), patient will remain on study and continue to receive AZT; if stable disease or no response, patient will be taken off study. Reevaluation at 16 weeks from start of study will be done. If CR or PR, the patient will continue AZT for 1 year. If there is no change or progression of disease, or if the patient develops evidence of systemic lymphomatous disease, patient will be taken off study.