Phase II trial of recurrent primary CNS lymphoma (PCNSL) treated with pemetrexed
Authors: J. K. Altman, C. Tellez, J. Chandler, R. M. Levy, C. Getch, R. Cohn, L. Gallot, M. Marymont, S. A. Grimm, J. J. Raizer
Journal: Journal of Clinical Oncology (2008)

2075 Background: Using high-dose methotrexate based regimens; median survival for patients with PCNSL is up to 60 mo. Approximately 50% of patients will relapse within 2 yrs. No standard therapy exists for relapsed patients but numerous regimens have been used with variable results. In addition to inhibiting dihydrofolate reductase, pemetrexed targets other sites of inhibition, giving it a broader spectrum of activity than methotrexate. This suggested that pemetrexed may be effective in PCNSL and lead to our use in a phase II trial. We update our results further substantiating the use of pemetrexed in PCNSL. Methods: All patients were treated with pemetrexed 900 mg/m2 every 3 weeks. Patients received dexamethasone 4 mg bid 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 1 prior chemotherapy regimen. Patients had to be > 18 years of age with KPS > 60. Adequate bone marrow, liver, and renal function were required. MRI was done every 6 weeks (1 cycle) and for patients who attained a CR, a maximum of 6 doses was given. Results: To date, 8 patients with recurrent PCNSL have been treated on this trial after signing IRB approved consent. All patients had large B Cell lymphoma except one had a low grade lymphoma. Conclusions: We report our experience of pemetrexed in 8 patients with recurrent PCNSL; all of whom had a radiographic response except the patient with low grade lymphoma who had SD. 3 patients had sustained CR, 1 of whom responded to a re-challenge with 2 other relapses. 62% of the patients had 6 or more cycles of therapy. This regimen is easy to administer with relatively minimal toxicity and should be considered for patients with relapsed PCNSL. Patient Characteristics Patient Age/ Sex # Prior therapy Response to pemetrexed # doses Length of Response Current status Toxicity 1 81/M 2 PR 2 Transient improvement after 1 dose then PD Deceased from Tumor gr 4: thrombocytopenia gr 3 infection, anemia, and leukopenia 2 52/F 4 PR 3 Transient improvement after 2 doses then PD Deceased from Tumor gr 4: thrombocytopenia and anemia gr 3: leukopenia and infection 3 72/M 1 PR 7 Major PR after 2 doses and sustained Deceased from sepsis/ unknown gr 3: cytopenias after 5th cycle 4 * 69/M 2 CR after 2 cycles 6 5 months Deceased from tumor gr 4: leukopenia gr 3: pain and infection 5 56/F 1 CR after 2 cycles 7 CR after 2 doses and sustained for over 11 months Alive No toxicity 6 69/M 1 SD 3 SD for 2+ months (time on study) Deceased from infection gr 3: leukopenia and thrombocytopenia 7 49/M 1 SD 6 SD for 4 months (time on study) Alive gr 3: transaminitis 8 39/M 1 CR 8 CR after 4 cycles and sustained for 3 months Alive No toxicity * At disease progression was treated with temodar and rituxan with progressive disease; retreatment with pemetrexed led to another CR, he again relapsed 4.5 mo later and responded to pemetrexed before he decided to stop treatment. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Lilly Oncology