Preradiation high-dose intravenous methotrexate with leucovorin rescue for untreated primary childhood brain tumors.
Although high-dose intravenous (IV) methotrexate (MTX) with leucovorin rescue (HDMTX) is effective for certain recurrent primary brain tumors, concern for inducing leukoencephalopathy has restrained its use as adjuvant therapy following therapeutic brain irradiation (RT). We have conducted a phase I to II clinical trial using four biweekly courses of HDMTX (8 g/m2) in a neoadjuvant setting in ten patients with newly diagnosed high-risk pediatric primary brain tumors. Four patients experienced an objective response after two to four courses of HDMTX alone (medulloblastoma, one; pineoblastoma, one; malignant cerebral astrocytoma, two). All ten patients subsequently received a course of therapeutic RT, and in seven cases, adjuvant chemotherapy with other agents. One patient acquired an acute transient encephalopathy before RT that completely resolved, and another developed a seizure disorder following RT associated with white matter abnormalities on a magnetic resonance imaging (MRI) scan. Five patients have survived a minimum of 33+ months, and four remain in continuous remission. The acute and delayed neurotoxicity of neoadjuvant HDMTX is acceptable, and we favor further use of this neoadjuvant approach in the context of a phase III trial.
Allen
J C
JC
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY.
Walker
R
R
Rosen
G
G
D000293:Adolescent; D000328:Adult; D001932:Brain Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000532:radiotherapy*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use*
D002955:Leucovorin; D008727:Methotrexate