LEPTOMENINGEAL METASTASES - RATIONALE FOR SYSTEMIC CHEMOTHERAPY OR WHAT IS THE ROLE OF INTRA-CSF-CHEMOTHERAPY

Malignant subarachnoid deposits complicate both primary central nervou s system (CNS) tumors and systemic neoplasms. Although the pathophysio logy of symptoms and signs can not be separated by the category of pri mary tumors that seeds the leptomeninges, the approach to therapy is n ot similar in primary CNS tumors and in systemic neoplasms. Standard t herapy for subarachnoid seeding in primary CNS tumors include conventi onal or high doses of systemic chemotherapy with various combinations of radiotherapy given either to limited fields or to the whole neuroax is. Direct administration of chemotherapy to the CSF is not being used . In contrast, whenever a systemic tumor seeds the subarachnoid space the standard approach includes intensive intra-CSF chemotherapy, radio therapy to limited or extended CNS fields and various combinations of systemic chemotherapy. The published experience with the conventional therapy is reviewed and is critically analyzed. Evidence indicating th at high dose systemic chemotherapy can replace intra-CSF treatment in some subgroups are also reviewed and the rationale for this approach i s specified. Recent experience in which intra-CSF therapy was prospect ively eliminated from the treatment protocol of leptomeningeal metasta ses of solid tumors reveals that the response rate and survival are si milar to those obtained by protocols that differed only by the inclusi on of intra-CSF chemotherapy. Patients who were treated by radiotherap y alone combined with systemic chemotherapy but without the intra-CSF therapy were spared the high rate of early and delayed complications d irectly related to intra-CSF therapy. Still, treatment outcome did not differ. Therefore, future research efforts and prospective clinical t rials should investigate the best chemotherapeutic schedules and their sequencing with radiotherapy or with more intensive complementary sys temic chemotherapy schemes. Newly designed drugs with long circulation time and improved CNS penetration may serve for this purpose.