Recurrent primary central nervous system lymphoma (PCNSL) treated with pemetrexed

Abstract

2086 Introduction: Untreated, survival in PCNSL is approximately 2 months. However using high dose methotrexate based regimens, median survival is up to 60 months. A significant number of patients relapse. There is currently no standard therapy, but many regimens have been used with variable results. Pemetrexed is a multi-targeted anti-folate agent approved for first line treatment of malignant pleural mesothelioma and second-line for locally advanced or metastatic non-small cell lung cancer. A phase II trial was initiated for patients with recurrent gliomas, PCNSL or brain metastases. Pemetrexed, in addition to inhibiting dihydrofolate reductase, targets other sites of inhibition, giving it a broader spectrum of activty. This suggests that pemetrexed could be effective in PCNSL. Patients and Methods: The dose of pemetrexed used was 900 mg/m2 every 3 weeks; based on phase I data where the MTD was 800 mg/m2 in heavily pretreated patients and not reached in lightly pretreated patients. Patients received dexamethasone 4 mg twice daily on the day before, the day of, and the day after each infusion of pemetrexed and supplemental folic acid and B12. Eligibility criteria for PCNSL patients included failure of at least one prior chemotherapy regimen. Patients had to be > 18 year of age with KPS status of > 60. Adequate bone marrow, liver, and renal function were required. An MRI was done every 6 weeks and for patients who attained a CR, a maximum of six doses was given. Results: To date, five patients with recurrent PCNSL have been treated on this trial after signing IRB approved consent. Patient Characteristics Discussion: We report our experience of pemetrexed in 5 patients with recurrent PCNSL. Toxicity has been minimal except in the one patient who was heavily pretreated (including a stem cell transplant). Activity was seen in all patients but transient in two. Pemetrexed is active in relapsed PCNSL. The optimal dose and schedule need to be determined, as well as activity in a larger group of patients. We continue to enroll patients in this study. [Table: see text] No significant financial relationships to disclose.