title: Temozolomide after radiotherapy for newly diagnosed high-grade glioma and unfavorable low-grade glioma in children.
abstract: Chemotherapy is commonly used in the treatment of children with high-grade glioma, although its usefulness is uncertain. We conducted a multi-institutional study to evaluate the efficacy of temozolomide given after radiotherapy in children with newly diagnosed high-grade glioma and unfavorable low-grade glioma (gliomatosis cerebri or bithalamic involvement). Optional window therapy of intravenous irinotecan (10 doses of 20 mg/m2 per cycle x 2) was given over 6 weeks. The 5-day schedule of temozolomide (200 mg/m2 per day) started 4 weeks after the completion of radiotherapy and continued for a total of 6 cycles. Thirty-one eligible patients (median age: 12.3 years) participated. Tumors most commonly involved cerebral hemispheres (n = 13, 42%) and thalamus (n = 14, 45%). Whereas six patients underwent radical resection, the remainder had limited surgery, including biopsy (n = 14, 45%). The predominant histologic diagnoses were glioblastoma multiforme (n = 15, 48%) and anaplastic astrocytoma (n = 10, 32%). Two patients had bithalamic grade II astrocytoma. Twenty-seven patients received radiotherapy (median dose: 59.4 Gy), including craniospinal irradiation in 3 because of leptomeningeal spread. Four patients did not receive radiotherapy in this study because of consent withdrawn (n = 2), toxicity during window therapy (n = 1), or at the physician's discretion (n = 1). Twenty-three patients received 112 cycles of temozolomide therapy. The 2-year progression-free and overall survival estimates were 11 +/- 5% and 21 +/- 7%, respectively. Although the heterogeneity of prognostic factors in our patients made assessment of treatment outcome more difficult, the addition of 6 cycles of temozolomide after radiotherapy did not seem to alter the poor outcome of these patients.
authors.affiliation: Department of Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA. alberto.broniscer@stjude.org
authors.forename: Alberto
authors.initials: A
authors.lastname: Broniscer
authors.forename: Murali
authors.initials: M
authors.lastname: Chintagumpala
authors.forename: Maryam
authors.initials: M
authors.lastname: Fouladi
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Krasin
authors.forename: Mehmet
authors.initials: M
authors.lastname: Kocak
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Bowers
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Iacono
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Merchant
authors.forename: Clinton F
authors.initials: CF
authors.lastname: Stewart
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Houghton
authors.forename: Larry E
authors.initials: LE
authors.lastname: Kun
authors.forename: Davonna
authors.initials: D
authors.lastname: Ledet
authors.forename: Amar
authors.initials: A
authors.lastname: Gajjar
mesh_terms: D000293:Adolescent; D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy; D006801:Humans; D000077146:Irinotecan; D008297:Male; D016019:Survival Analysis; D000077204:Temozolomide; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D003606:Dacarbazine; D002166:Camptothecin; D000077204:Temozolomide