Role of temozolomide after radiotherapy for newly diagnosed diffuse brainstem glioma in children: results of a multiinstitutional study (SJHG-98).
BACKGROUND
The role of chemotherapy in the treatment of children with newly diagnosed diffuse brainstem glioma is uncertain. In the current study, the authors tested the efficacy of temozolomide treatment after radiotherapy (RT) in this setting.


METHODS
Patients ages 3-21 years were eligible for the current multiinstitutional study. An optional window therapy regimen consisting of 2 cycles of intravenous irinotecan (10 doses of 20 mg/m2 per day separated by 2 days of rest per cycle) was delivered over 6 weeks and was followed by conventionally fractionated RT. The 5-day schedule of temozolomide (200 mg/m2 per day) was initiated 4 weeks after RT and was continued for a total of 6 cycles. The pharmacokinetics of temozolomide and its active metabolite, 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide (MTIC), were analyzed during Cycles 1 and 3.


RESULTS
Thirty-three patients (median age at diagnosis, 6.4 years) were enrolled. Of the 16 patients who received window therapy, 6 had irinotecan treatment discontinued due to clinical progression (n=5) or toxicity (n=1); the remaining 10 experienced disease stabilization after 2 cycles. All patients completed RT (median dose, 55.8 gray). Twenty-nine patients received a combined total of 125 cycles of temozolomide. Grade 3/4 neutropenia and thrombocytopenia occurred in 33% and 29% of all temozolomide cycles, respectively. In approximately one-third of the cycles, dose reduction was required due to myelosuppression. No correlation was demonstrated between temozolomide/MTIC exposure and myelosuppression at the conclusion of Cycle 1. All patients died of disease progression (median survival, 12 months). The estimated 1-year survival rate was 48% (standard error, 8%).


CONCLUSIONS
The administration of temozolomide after RT did not alter the poor prognosis associated with newly diagnosed diffuse brainstem glioma in children.
Broniscer
Alberto
A
Department of Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. alberto.broniscer@stjude.org
Iacono
Lisa
L
Chintagumpala
Murali
M
Fouladi
Maryam
M
Wallace
Dana
D
Bowers
Daniel C
DC
Stewart
Clinton
C
Krasin
Matthew J
MJ
Gajjar
Amar
A
D000284:Administration, Oral; D000293:Adolescent; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D020295:Brain Stem Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002648:Child; D002675:Child, Preschool; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D008297:Male; D000077204:Temozolomide; D016896:Treatment Outcome
D018906:Antineoplastic Agents, Alkylating; D000077146:Irinotecan; D003606:Dacarbazine; D002166:Camptothecin; D000077204:Temozolomide