title: Very high-dose methotrexate (33.6 g/m(2)) as central nervous system preventive therapy for childhood acute lymphoblastic leukemia: results of National Cancer Institute/Children's Cancer Group trials CCG-191P, CCG-134P and CCG-144P.
abstract: Between 1977 and 1991, the Children's Cancer Group and the National Cancer Institute conducted three trials of very high-dose methotrexate (33.6 g/m2; VHD-MTX) in place of cranial radiation (CRT) as central nervous system (CNS) preventive therapy, and assessed efficacy, acute toxicity and long-term neurocognitive outcome. CCG-191P compared VHD-MTX to CRT plus intrathecal methotrexate (IT-MTX) in 181 patients and demonstrated equivalent survival. However, patients treated with CRT had poorer performance on neurocognitive testing over time. CCG-134P evaluated the addition of intensified systemic and intrathecal therapy to VHD-MTX in 128 patients with high-risk acute lymphoblastic leukemia (ALL) and demonstrated reduced CNS relapse compared to the CCG-191P trial, but equivalent survival. CCG-144P compared VHD-MTX to IT-MTX alone in 175 patients with average-risk ALL and demonstrated equivalent survival. VHD-MTX was associated with significant toxicities, particularly neutropenia, transient hepatic dysfunction and sepsis. VHD-MTX achieved similar survival to other CNS-directed therapies without the long-term impact on intelligence, but with substantial acute toxicities.
authors.affiliation: Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Nathan
authors.forename: Trish
authors.initials: T
authors.lastname: Whitcomb
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Wolters
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: Frank M
authors.initials: FM
authors.lastname: Balis
authors.forename: Pim
authors.initials: P
authors.lastname: Brouwers
authors.forename: Sally
authors.initials: S
authors.lastname: Hunsberger
authors.forename: James
authors.initials: J
authors.lastname: Feusner
authors.forename: Harland
authors.initials: H
authors.lastname: Sather
authors.forename: James
authors.initials: J
authors.lastname: Miser
authors.forename: Lorrie F
authors.initials: LF
authors.lastname: Odom
authors.forename: David
authors.initials: D
authors.lastname: Poplack
authors.forename: Gregory
authors.initials: G
authors.lastname: Reaman
authors.forename: W Archie
authors.initials: WA
authors.lastname: Bleyer
mesh_terms: D000293:Adolescent; D000328:Adult; D016543:Central Nervous System Neoplasms / Q000517:prevention & control*; D002648:Child; D002675:Child, Preschool; D003071:Cognition / Q000187:drug effects; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D010865:Pilot Projects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D012306:Risk; D016896:Treatment Outcome
chemical_list: D008727:Methotrexate