Carboxypeptidase G₂ rescue after high-dose methotrexate

Purpose: This study was a pilot project to assess the safety and efficacy of carboxypeptidase G₂ (CPG2) rescue from high-dose (HD) methotrexate (MTX) in patients with recurrent cerebral lymphoma. Patients and Methods: Four patients with recurrent primary CNS lymphoma (PCNSL) were studied. Patients received 3.0 g/m² MTX infused over 2 hours. Twelve hours after the start of MTX, 50 U/kg CPG2 was infused; a second dose of CPG2 was given 6 hours after the first. Blood and CSF were collected and assayed for levels of MTX, CPG2, and 2,4-diamino-N¹⁰-methylpteroic acid (DAMPA), a cleavage product of MTX after CPG2. Serum was collected fur at least 2 weeks after administration of MTX-CPG2 to assess anti-CPG2 activity antibodies. Results: All patients had at least a 2-log decline in plasma MTX levels to the subtherapeutic range within 5 minutes of CPG2 administration. The second dose of CPG2 did not further diminish the already low plasma MTX level. DAMPA appeared and was detected as the plasma MTX concentration decreased, CSF MTX concentration remained elevated for 4 hours after CPG2, and its decline followed first-order kinetics. Anti-CPG2 activity antibodies were not detected in any patient. No MTX or CPG2 toxicity was observed. Conclusion: CPG2 rescue is a safe, effective alternative to leucovorin rescue after HD MTX and may prove particularly useful fur the treatment of MTX-sensitive CNS tumors, as it does not affect CSF MTX levels.