A Chemotherapeutic Approach to CNS Lymphoma and Leukaemia by the Systemic Administration of High Doses of Antimetabolites

Abstract

Primary and metastatic tumours in the central nervous system have generally been refractory to successful treatment with chemotherapeutic agents. A few drugs have the capacity for traversing the blood-brain barrier by virtue of their lipid solubility. These include the nitrosoureas and corticosteroids. The nitrosoureas have been used extensively in the treatment of primary brain tumours with only marginal benefit, nor have they been found to be successful as prophylactic agents against central nervous system leukaemia. To date, few chemotherapeutic agents have been found to be effective against primary brain tumours. In comparison to primary neoplastic disease there is a significantly larger number of patients with metastases to the CNS. The most common tumours include carcinoma of the lung, breast, melanoma, and lymphoma. This complication has appeared more commonly as the therapy for systemic disease as chemotherapy improves the longterm disease-free survival. The incidence of late central nervous system metastases has been noted in tunours in which it was previously a rare complication. This is especially true in testicular tumours, sarcomas, and more recently, ovarian carcinoma (Mayer et al., 1978).