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Chemoradiotherapy for primary CNS lymphoma

An intent-to-treat analysis with complete follow-up

From Memorial Sloan-Kettering Cancer Center, New York, NY.

Address correspondence and reprint requests to Dr. Lauren E. Abrey, Department of Neurology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021; e-mail: abreyl{at}mskcc.org

Objective: To assess the efficacy and safety of a preradiation chemotherapy regimen in patients with primary CNS lymphoma (PCNSL), with emphasis on long-term outcomes.

Methods: In this prospective phase II trial, patients with a new diagnosis of PCNSL received two cycles of intrathecal (12 mg) and IV (1 g/m²) methotrexate (MTX), thiotepa (30 mg/m²), and procarbazine (75 mg/m²), prior to whole-brain radiotherapy (RT).

Results: Seventeen patients were enrolled (ages 26 to 71, median 53). Median Karnofsky performance scale score was 70. After chemotherapy, 7 patients (41%) had a complete response (CR) and 7 (41%) a partial response (PR). After RT, 13 (76%) patients achieved a CR, 2 (12%) a PR, and 2 (12%) had disease progression. Relapse occurred in 7 (41%) patients; median disease-free survival was 18 months. Fifteen (88%) patients have died: 8 (47%) from PCNSL, 5 (29%) from neurotoxicity, and 2 (12%) from unknown causes. Median overall survival was 32 months. Two patients (12%) are alive and disease free at 12 years follow-up. Nephrotoxicity was a minor complication, but grades 3 and 4 myelosuppression were found in 5 (29%) patients.

Conclusions: This regimen resulted in an efficacy and toxicity profile comparable to other combined modality treatments, despite the relatively low dose of methotrexate. It may be a useful option in patients unable to tolerate higher doses. Procarbazine and thiotepa are potential candidates for incorporation into chemotherapy regimens aiming to decrease the incidence of neurotoxicity. First relapse and neurotoxicity within 2 years of diagnosis seem to be critical for predicting long-term outcomes.

Received April 23, 2004. Accepted in final form September 13, 2004.

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