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Methotrexate Induction Therapy Followed by High-Dose Chemotherapy with Autologous Stem Cell Rescue May Cause Less Neurotoxicity for Primary CNS Lymphoma Patients

Methotrexate-based chemotherapy followed by high-dose chemotherapy with autologous stem-cell rescue may be a feasible treatment approach for primary central nervous system (CNS) lymphoma without causing significant neurotoxicity.

A combination of methotrexate-based chemotherapy and cranial radiation is currently the best available therapy for primary CNS lymphoma, a form of aggressive non-Hodgkin's lymphoma. However, recurrence of disease is common, and neurotoxicity resulting from cranial radiation occurs frequently in older patients and long-term survivors. Thus, the efficacy of treatment needs to be improved while eliminating the need for cranial irradiation.

Lauren E. Abrey, Memorial Sloan-Kettering Cancer Center, New York, United States, and colleagues performed a multicentre phase II trial to test the efficacy and safety of high-dose methotrexate and cytarabine chemotherapy followed by consolidative high-dose chemotherapy (HDT) with autologous stem-cell transplantation (ASCT) in patients with newly diagnosed primary CNS lymphoma.

HDT with ASCT has been previously shown to be an effective salvage treatment for relapsed or primary refractory non-Hodgkin's lymphoma.

In the present study, this therapy included carmustine, etoposide, cytarabine, and melphalan, a regimen that can be administered safely to older patients. This is of particular importance when treating patients with primary CNS lymphoma, because their median age is 60 years.

Eighteen men and 10 women with a median age of 53 years were administered induction chemotherapy consisting of high-dose methotrexate 3.5 g/m² followed by cytarabine 3g/m² daily for 2 days. Fourteen patients were determined to be chemoresponsive by magnetic resonance imaging and were were subsequently treated with ASCT and HDT.

Of the 14 patients who completed HDT and ASCT, six remain disease free at last follow-up. The median event-free survival time for all patients is 5.6 months and 9.3 months for the patients receiving HDT and ASCT. Median overall survival is not yet assessable.

"Significantly, no patient has developed cognitive impairment as a consequence of treatment," the researchers note. In addition, they report that patients tolerated both phases of treatment with acceptable levels of toxicity.

They conclude that, "the use of HDT and ASCT is clearly feasible in this patient population." However, they note that the radiographic response to the induction-phase chemotherapy was lower than expected, and 50% of patients experienced disease relapse within a few months of ASCT. Based on these observations, they suggest that, "additional study using a more intensive, conventional induction regimen and possibly a different HDT conditioning regimen...is warranted."
J Clin Oncol 2003 Nov 15;21:22:4151-6. "Intensive Methotrexate and Cytarabine Followed by High-Dose Chemotherapy With Autologous Stem-Cell Rescue in Patients With Newly Diagnosed Primary CNS Lymphoma: An Intent-to-Treat Analysis"

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