Pemetrexed in the treatment of relapsed/refractory primary central nervous system lymphoma

BACKGROUND: Despite initial treatment with high-dose methotrexate-based regimens, many patients with primary central nervous system lymphoma (PCNSL) relapse and die from their disease. No standard of care exists at progression or relapse, but chemotherapy and in some cases radiation are usually used. Pemetrexed is a multitargeted antifolate, similar to methotrexate, but with a broader spectrum of activity. Because methotrexate is an integral part of PCSNL treatment, the authors assessed the antitumor activity and safety of pemetrexed in recurrent PCNSL. METHODS: Patients with relapsed/refractory PCNSL were enrolled in this trial. Treatment consisted of pemetrexed 900 mg/m ² given every 3 weeks with low-dose dexamethasone, folate, and B12 supplementation. Each cycle was 6 weeks, and follow-up imaging was done before each new cycle. Treatment was continued until complete remission, progression, or toxicity. RESULTS: Eleven patients were treated, with a median age of 69.8 years and Karnofsky performance status of 70%; 10 of 11 patients had failed prior high-dose methotrexate. The median number of pemetrexed cycles given was 5, with an associated overall response rate of 55% and disease control rate of 91%. The 6-month progression-free survival (PFS) was 45%, median PFS was 5.7 months, and median overall survival was 10.1 months. Toxicities were primarily hematologic and infectious. CONCLUSIONS: Pemetrexed has single-agent activity in relapsed/refractory PCNSL. Toxicities were seen likely because of the higher than standard dose used. Further investigation of this agent or other multitargeted antifolates in PCNSL is warranted to determine optimal dose and efficacy in a more homogeneous population.