Temozolomide as salvage treatment in primary brain lymphomas

Abstract

Methotrexate (MTX)-based chemotherapy extends survival in patients with primary brain lymphomas, but it is not clear whether multiagent chemotherapy is superior to MTX alone. Treatment options for patients with recurrent primary brain lymphoma are limited; there is no standard second-line chemotherapy. New chemotherapeutic agents with clear activity in brain lymphoma are needed for treatment of recurrent disease. We report the results of a phase II trial assessing activity of the alkylating agent temozolomide in immunocompetent patients with recurrent primary brain lymphomas, previously treated with high-dose MTXcontaining chemotherapy and/or radiotherapy. A median of two courses (range 1 -12) of temozolomide 150 mg m À2 day À1 , for 5 days every 4 weeks was administered to 36 patients yielding nine complete and two partial responses (response rate: 31%; 95% confidence interval 16 -46%). One-year survival was 31% (95% confidence interval 16 -46%). Toxicity was negligible. We conclude that temozolomide is active in recurrent primary brain lymphomas and should further be evaluated in this disease, perhaps in combination with MTX as initial treatment.

Limited role of surgery in the management of primary central nervous system lymphoma (Review)

“…However, retreatment may raise the risk for neurotoxicity. Salvage monochemotherapy with temozolomide or topotecan in patients previously managed with an RT-containing approach is supported by prospective trials, whereas the combination chemotherapy remains investigational (62)(63)(64). High-dose chemotherapy supported by ASCT and the use of intrathecal chemotherapy in patients with meningeal failure hold promise to be further addressed in prospective trials (64).…”

Treatment approaches for primary CNS lymphomas

“…Mono-chemotherapy with temozolomide is an active treatment for patients with relapsed or refractory PCNSL [37]. In clinical practice, its favourable tolerability profile makes this drug a valid option also for elderly and frail patients.…”

“…[37,74] prospective 36 60 86% 28% 25 + 6% 2.8 4.0 31% 6% 3% 3% Methotrexate [75] retrospective 22 58 14% -73 + 19% 26 26 70% 5% 5% 36% Temozolomide + Rituximab [68] retrospective 15 69 13% 67% 40 + 13% 2.2 10.5 58% 7% 27% 7%…”

“…For instance, a single-arm Phase II study has demonstrated that the combination of MTX and temozolomide is feasible and is associated with some durable responses. Temozolomide, an oral alkylating agent, is a suitable candidate for combination therapies because it permeates the BBB, has in vitro additive cytotoxic activity with radiotherapy [37] and shows only mild toxicity.…”

Primary central nervous system lymphoma: what a neurologist/neurosurgeon should know?

“…Temozolomide, an oral alkylating agent already used for glioblastoma, has shown high response rates even in patients with refractory or relapsed disease after high dose of MTX 22,23 . Prospective trials evaluating temozolomide as first line treatment for this entity are under way.…”