Salvage treatment with temozolomide in refractory or relapsed primary central nervous system lymphoma and assessment of the MGMT status Salvage treatment with temozolomide in refractory or relapsed primary central nervous system lymphoma and assessment of the MGMT status
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High-dose methotrexate (HD-MTX) is effective in the initial treatment of primary central nervous system lymphoma (PCNSL). Since the treatment options in patients with progressive or recurrent PCNSL are limited, their prognosis is remains poor. Temozolomide, a well-tolerated oral alkylating agent that permeates the blood brain barrier, is effective against malignant glioma and recurrent PCNSL. The gene for the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT), which is closely related to cellular sensitivity to alkylating agents, is inactivated by promoter hypermethylation. We evaluated the results of temozolomide treatment and the methylation status of the promoter region of the MGMT gene in 17 patients (median age 68 years) with refractory or relapsed PCNSL. They were immunocompetent and had received initial treatment with HD-MTX (3.5 g/m2) with or without irradiation. All were treated with temozolomide 150 to 200 mg/m2, for 5 days in the course of 28 days; treatment was continued until disease progression. We observed 5 complete remissions, 5 partial responses and stable disease, and 7 disease progressions. Median overall survival after the temozolomide treatment was 6.7 months. One patient manifested grade 3 neutropenia and thrombocytopenia. Eleven tumor specimens were available for MGMT analysis. MGMT promoter methylation (mMGMT) in the tumor tissue was found in 4 (36.4%), the other 7 harbored a non-methylated MGMT promoter (nmMGMT). There was no statistically significant difference in median overall survival between patients with mMGMT (11.1 months) and nmMGMT (6.7 months)(p=0.63). Although some patients were elderly and had been heavily pre-treated, temozolomide produced a complete response in 29% and was well tolerated without any major toxicity.
- Journal of Neuro-Oncology
Journal of Neuro-Oncology 106(1), 155-160, 2012-01
Kluwer Academic Publishers