title: Temozolomide in the treatment of high-grade gliomas in children: a report from the Children's Oncology Group.
abstract: To determine whether temozolomide is an active agent in the treatment of children with high-grade astrocytomas and whether survival is influenced by the expression of the O6-methylguanine-methyltransferase gene (MGMT) in these patients. In the Children's Oncology Group study ACNS0126, 107 patients with a diagnosis of anaplastic astrocytoma (AA), glioblastoma multiforme (GBM), or gliosarcoma were enrolled. All patients underwent concomitant chemoradiotherapy with temozolomide, followed by adjuvant chemotherapy with temozolomide. The outcomes were compared with those of children treated in Children's Cancer Group (CCG) study CCG-945. Formalin-fixed, paraffin-embedded tumor tissue was available in 71 cases for immunohistochemical analysis of MGMT expression. Ninety patients were deemed eligible, 31 with AA, 55 with GBM, and 4 with other eligible diagnoses. The 3-year event-free survival (EFS) and overall survival (OS) rates were 11 ± 3% and 22 ± 5%, respectively. There was no evidence that temozolomide given during radiation therapy and as adjuvant therapy resulted in improved EFS compared with that found in CCG-945 (p = 0.98). The 3-year EFS rate for AA was 13 ± 6% in ACNS0126 compared with 22 ± 5.5% in CCG-945 (p = 0.95). The 3-year EFS rate for GBM was 7 ± 4% in ACNS0126 compared with 15 ± 5% in CCG-945 (p = 0.77). The 2-year EFS rate was 17 ± 5% among patients without MGMT overexpression and 5 ± 4% among those with MGMT overexpression (p = 0.045). Temozolomide failed to improve outcome in children with high-grade astrocytomas. MGMT overexpression was adversely associated with survival.
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA. kcohen@jhmi.edu
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Cohen
authors.forename: Ian F
authors.initials: IF
authors.lastname: Pollack
authors.forename: Tianni
authors.initials: T
authors.lastname: Zhou
authors.forename: Allen
authors.initials: A
authors.lastname: Buxton
authors.forename: Emiko J
authors.initials: EJ
authors.lastname: Holmes
authors.forename: Peter C
authors.initials: PC
authors.lastname: Burger
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Brat
authors.forename: Marc K
authors.initials: MK
authors.lastname: Rosenblum
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Hamilton
authors.forename: Robert S
authors.initials: RS
authors.lastname: Lavey
authors.forename: Richard L
authors.initials: RL
authors.lastname: Heideman
mesh_terms: D000293:Adolescent; D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000188:drug therapy* / Q000532:radiotherapy; D018316:Gliosarcoma / Q000188:drug therapy* / Q000532:radiotherapy; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000378:metabolism; D011879:Radiotherapy Dosage; D015996:Survival Rate; D000077204:Temozolomide; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D019853:O(6)-Methylguanine-DNA Methyltransferase; D000077204:Temozolomide