Interferon-beta, MCNU, and conventional radiotherapy for pediatric patients with brainstem glioma.
BACKGROUND
Most children with brainstem glioma die within 2 years of diagnosis, and the median survival time for patients with this condition is less than 1 year. The role of chemotherapy in the treatment of children with brainstem glioma is not well defined. The primary aim of this study is to evaluate the effects of treatment with interferon-beta (IFN-beta), ranimustine (MCNU), and radiotherapy (IMR therapy) administered to brainstem glioma patients treated at our institution. We also determined patient response to IMR therapy by evaluating O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation in serum DNA.


METHODS
We retrospectively reviewed 15 patients who were newly diagnosed to have brainstem tumors and were administered IFN-beta (1-2 MIU/day, days 1-7; 0.5-1 MIU/day, days 8-14) and MCNU (80 mg/m(2) on day 2) concurrently with conventional radiotherapy. Responses were assessed by MRI scan, and data on clinical course and toxicity were obtained from the medical records. The MGMT promoter methylation in serum DNA of five patients was assayed by methylation-specific PCR.


RESULTS
Of the 15 patients, partial response, stable disease, and progressive disease were noted in 5 patients each. The median overall survival time and the median progression-free survival time were 14.7 and 4.6 months, respectively. The protocol was not terminated in any of the patients because of hematological toxicity, nephrotoxicity, or neurotoxicity. The MGMT promoter methylation status in the serum appeared to correlate with a positive response to IMR therapy.


CONCLUSIONS
The IMR combination therapy is well tolerated and may be a promising treatment for brainstem glioma.
Ohno
Masasuke
M
Department of Neurosurgery, Nagoya University, Nagoya, Japan.
Natsume
Atsushi
A
Fujii
Masazumi
M
Ito
Motokazu
M
Wakabayashi
Toshihiko
T
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D020295:Brain Stem Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D016190:Carboplatin / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation / Q000187:drug effects; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005910:Glioma / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D016899:Interferon-beta / Q000008:administration & dosage; D008279:Magnetic Resonance Imaging; D008297:Male; D009607:Nitrosourea Compounds / Q000008:administration & dosage; D012189:Retrospective Studies; D000077204:Temozolomide; D016896:Treatment Outcome
D009607:Nitrosourea Compounds; D005047:Etoposide; D016899:Interferon-beta; D003606:Dacarbazine; D016190:Carboplatin; C020766:ranimustine; D000077204:Temozolomide