DeAngelis L M, Tong W P, Lin S, Fleisher M, Bertino J R
Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
J Clin Oncol. 1996 Jul;14(7):2145-9. doi: 10.1200/JCO.1996.14.7.2145.
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.
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 for at least 2 weeks after administration of MTX-CPG2 to assess anti-CPG2 activity antibodies.
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.
CPG2 rescue is a safe, effective alternative to leucovorin rescue after HD MTX and may prove particularly useful for the treatment of MTX-sensitive CNS tumors, as it does not affect CSF MTX levels.
本研究是一项试点项目，旨在评估羧肽酶G2（CPG2）解救复发性脑淋巴瘤患者大剂量（HD）甲氨蝶呤（MTX）的安全性和有效性。
对4例复发性原发性中枢神经系统淋巴瘤（PCNSL）患者进行了研究。患者接受2小时内输注3.0 g/m² MTX。MTX开始输注12小时后，输注50 U/kg CPG2；在首次给药6小时后给予第二剂CPG2。采集血液和脑脊液，检测MTX、CPG2和2,4-二氨基-N10-甲基蝶酸（DAMPA，CPG2作用后MTX的裂解产物）的水平。在给予MTX-CPG2后至少2周采集血清，以评估抗CPG2活性抗体。
所有患者在给予CPG2后5分钟内血浆MTX水平至少下降2个对数至亚治疗范围。第二剂CPG2并未进一步降低已经很低的血浆MTX水平。随着血浆MTX浓度降低，DAMPA出现并被检测到。CPG2给药后4小时脑脊液MTX浓度仍保持升高，其下降遵循一级动力学。在任何患者中均未检测到抗CPG2活性抗体。未观察到MTX或CPG2毒性。
CPG2解救是HD MTX后亚叶酸解救的一种安全、有效的替代方法，对于MTX敏感的中枢神经系统肿瘤治疗可能特别有用，因为它不影响脑脊液MTX水平。
