Patients with AIDS are well known to develop neoplastic complications of which Kaposi's sarcoma, non-Hodgkin lymphoma, and primary CNS lymphoma (PCL) are most common. These malignancies are a significant cause of morbidity and mortality in patients with AIDS. The incidence of non- Hodgkin lymphoma and in particular PCL is sharply on the rise. Current therapeutic approaches in patients with AIDS-related malignancies are toxic and it is the rare patient who benefits from therapy in terms of significant palliation of symptoms or prolongation of survival. This proposal will investigate a combined modality regimen incorporating oral combination chemotherapy, granulocyte-colony stimulating factor (G-CSF) support, and radiation. The rationale for administering oral combination chemotherapy consisting of lomustine (CCNU) and procarbazine for one cycle prior to radiation is based on the preliminary results this group has reported in 18 patients with systemic AIDS-related lymphoma. This pilot study confirmed that oral CCNU, etoposide, cyclophosphamide and procarbazine is active in AIDS-related lymphoma with an objective response rate of 61% and median survival of 7 months. More importantly there are several clinical advantages to using an oral regimen in HIV-infected patients. Nuclear Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) will play a primary role in this study. Changes in PCL to the proposed therapy regimen will be monitored by MRI and proton MRS. Volumetric analysis of neuroanatomical changes in PCL determined by MRI will be correlated with biochemical changes monitored by proton (MRS). It is our hypothesis that quantitative proton NMR spectroscopy at diagnosis and during therapy will provide a metabolic signature of PCL which will yield clinical and prognostic information. A secondary objective of this proposal will be to perform a prospective quality of life assessment on patients enrolled in this trial. Investigators of this proposal were the first to incorporate prospective quality of life assessments in a clinical trial of chemotherapy for AIDS-related lymphoma in their initial pilot study. Finally, all aspects of this grant proposal are based on clinical and basic science investigations, which have already been piloted and published by the participating investigators in this project.
