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Salvage therapy with temozolomide in an immunocompetent patient with primary brain lymphoma.

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). An immunocompetent 65-year-old male with multifocal diffuse large B-cell primary brain lymphoma was scheduled to receive chemotherapy with procarbazine (100 mg/m per day on days 1–14), vincristine (2 mg on day 1), and highdose methotrexate (3 g/m 2 on days 3 and 10). After 7 days, the treatment was terminated because of renal toxicity, congestive heart failure, and a 15% increase in body weight. The patient was referred to radiotherapy. He received a dose of 41.4 Gy to the whole brain and a dose of 54 Gy to the enhanced lesions; a partial response was obtained. The residual disease was treated with four courses of lomustine (CCNU) (100 mg/m on day 1), vincristine (2 mg on days 8, 22, and 36), and high-dose cytarabine (3 g/m on days 9, 23, and 37), and a complete response was achieved. Treatment was poorly tolerated, without improvement in performance status (Eastern Cooperative Oncology Group [ECOG] 4 3). Three months later, recurrence of the disease at the splenium of the corpus callosum was diagnosed (Fig. 1, A and B). After obtaining written informed consent from the patient, he was treated with four courses of temozolomide (150 mg/m per day for 5 days every 4