Pharmacotherapy for primary CNS lymphoma: progress beyond methotrexate?

Studies conducted in the 1990s have established that high-dose methotrexate-based chemotherapy added to whole-brain radiotherapy improves survival in primary CNS lymphoma (PCNSL). However, radiotherapy-related delayed neurotoxicity has emerged as a serious complication of chemo-radiotherapy, particularly in the elderly. Unfortunately, omitting radiotherapy results in decreased progression-free survival, and therefore establishing more effective chemotherapy regimens is necessary in order to improve the number of long-term remissions. Recent studies have suggested that a combination of drugs is superior to single-agent methotrexate, but the optimal chemotherapy combination and the role of alternative consolidation treatments such as reduced-dose radiotherapy and high-dose chemotherapy with stem cell rescue remain to be defined. In this article, we review the multiple chemotherapy options reported in newly diagnosed and in progressive/refractory PCNSL, including recently reported and ongoing clinical trials, as well as future perspectives.