Originally published as JCO Early Release 10.1200/JCO.2003.03.108 on November 3 2003

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High-Dose Methotrexate-Based Chemotherapy Followed by Consolidating Radiotherapy in Non–AIDS-Related Primary Central Nervous System Lymphoma: European Organization for Research and Treatment of Cancer Lymphoma Group Phase II Trial 20962

Philip M.P. Poortmans, Hanneke C. Kluin-Nelemans, Hanny Haaxma-Reiche, Mars Van’t Veer, Mads Hansen, Pierre Soubeyran, Martin Taphoorn, José Thomas, Martin Van den Bent, Martin Fickers, Gustaaf Van Imhoff, Cynthia Rozewicz, Ivana Teodorovic, Martine van Glabbeke

From the Dr Bernard Verbeeten Institute, Tilburg; University Hospital Groningen, Groningen; Daniel den Hoed Kliniek, Rotterdam; Universitair Medisch Centrum, Utrecht; Atrium Medisch Center, Heerlen; University Medical Center, Leiden, the Netherlands; Rigshospitalet, Copenhagen, Denmark; Institut Bergonie, Bordeaux, France; University Hospital Gasthuisberg, Leuven; and the European Organization for Research and Treatment of Cancer Data Center, Brussels, Belgium.

Address reprint requests to Philip M.P. Poortmans, MD, Dr Bernard Verbeeten Instituut, PO Box 90120, 5000 LA Tilburg, the Netherlands; e-mail: poortmans.ph{at}bvi.nl.

Purpose: To confirm the feasibility and estimate the efficacy of methotrexate (MTX), teniposide, carmustine, and methylprednisolone (MBVP) chemotherapy combined with radiotherapy (RT) for patients with non–AIDS-related primary CNS lymphoma (PCNSL) treated in a multicenter setting.

Patients and Methods: Treatment consisted of two cycles of MBVP (MTX 3 g/m² days 1 and 15, teniposide 100 mg/m² days 2 and 3, carmustine 100 mg/m² day 4, methylprednisolone 60 mg/m² days 1 to 5, and two intrathecal injections of MTX 15 mg, cytarabine 40 mg, and hydrocortisone 25 mg) followed by 40 Gy of RT. Primary end points were response and safety of this regimen.

Results: Twelve centers included 52 patients who were all analyzed on an intent-to-treat basis. Median follow-up of all patients was 27 months. One patient progressed and died before treatment, and five patients died during treatment. Four patients received RT after one cycle of chemotherapy, and 42 patients completed the entire treatment. Hematologic grade 3 and 4 toxicity was seen in 78% of patients for leukocytes and 24% of patients for platelets. The overall response rate of all 52 patients was 81%. Two patients who did not fulfill the criteria of objective response survived more than 1 year; one of them is still alive without disease. Eighteen patients died; 11 deaths were a result of tumor, five were probably treatment-related, one was caused by late leukoencephalopathy, and one was a result of intercurrent disease. Median estimated overall survival was 46 months.

Conclusion: MBVP followed by RT for PCNSL has a high response rate. However, the 10% toxic death rate during treatment in a multicenter setting underlines the need for highly specialized care.

Supported in part by a grant from the Dutch Cancer Foundation.

Presented in part at the Eighth International Conference on Malignant Lymphoma, Lugano, Switzerland, June 12–15, 2002.

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