Rosen G, Ghavimi F, Nirenberg A, Mosende C, Mehta B M
Cancer Treat Rep. 1977 Jul;61(4):681-90.
Eleven patients with brain tumors recurrent after surgery and radiation therapy were treated with high-dose methotrexate (MTX) (300-500 mg/kg) with citrovorum factor rescue (CFR). MTX was given as an iv infusion over 4 hours followed 2 hours later by oral CFR (10 mg every 6 hours X 12). MTX levels were measured in the serum, lumbar cerebrospinal fluid (CSF), and ventricular CSF at 0, 4, 12, 24, 48, and 72 hours from the start of the MTX infusion. MTX concentrations of greater than 10(-6) M were measured in the CSF over a period of 24 hours after the iv infusion. Peak CSF concentrations reached were greater than 10(-5) M. After the response to high-dose MTX with CFR was evaluated, vincristine (1.5 mg/m2) and a nitrosourea (methyl-CCNU or BCNU) were added to this treatment regimen. Two of four patients with recurrent pontine glioma and five of seven patients with recurrent medulloblastoma had favorable objective responses to treatment. It is suggested that high-dose MTX with CFR be cautiously considered for the primary treatment of intracranial neoplasms in children with the hope of increasing the cure rate for children with malignant brain tumors.
11例脑肿瘤患者在手术和放疗后复发，接受了大剂量甲氨蝶呤（MTX）（300 - 500mg/kg）并辅以甲酰四氢叶酸解救（CFR）治疗。MTX通过静脉输注4小时给予，2小时后口服CFR（每6小时10mg，共12次）。在MTX输注开始后的0、4、12、24、48和72小时测量血清、腰椎脑脊液（CSF）和脑室CSF中的MTX水平。静脉输注后24小时内，CSF中MTX浓度测量值大于10⁻⁶M。CSF峰值浓度达到大于10⁻⁵M。在评估了大剂量MTX联合CFR的反应后，将长春新碱（1.5mg/m²）和一种亚硝基脲（甲基环己亚硝脲或卡莫司汀）添加到该治疗方案中。4例复发性脑桥胶质瘤患者中有2例，7例复发性髓母细胞瘤患者中有5例对治疗有良好的客观反应。建议对于儿童颅内肿瘤的初始治疗谨慎考虑大剂量MTX联合CFR，以期提高儿童恶性脑肿瘤的治愈率。
