Salvage Therapy With Temozolomide in an Immunocompetent Patient With Primary Brain Lymphoma

Extract

Twenty years ago, it was reported that a patient with relapsed primary brain lymphoma had been successfully treated with high-dose methotrexate (1). Since then, this drug has become the cornerstone of therapy, changing the natural course of this malignancy (2). Several other drugs have been used sporadically, mainly in combination with high-dose methotrexate, without achieving an improvement in outcome compared with monochemotherapy. No other single-agent activity has been prospectively proven to be effective. Moreover, cytostatic drugs that cross the blood-brain barrier (e.g., cytarabine, procarbazine, and nitrosoureas) may produce severe neurotoxicity, mainly when combined with radiotherapy or administered to patients older than 60 years of age (3,4). The most efficient cytostatic drugs against extracerebral non-Hodgkin's lymphomas penetrate the blood-brain barrier poorly and produce systemic toxicity (2). So, the routine use of drugs with unproven activities or unproven additive effects greater than that of high-dose methotrexate alone is not advisable.

The use of new drugs that cross the blood-brain barrier and enhance the efficacy of high-dose methotrexate and radiotherapy with acceptable toxicity should be pursued in recurrent or refractory disease (5). Temozolomide, an oral alkylating agent, is a suitable candidate for clinical study because it permeates the blood-brain barrier, has in vitro additive cytotoxic activity with radiotherapy (6), and shows only mild toxicity, even in patients older than 60 years of age, who represent about 50% of primary brain lymphoma patients and have a high risk of complications (7).