Summary
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 × 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 Four patients did not receive radiotherapy in this study because of consent withdrawn (n = 2), toxicity during window therapy (n = 1), or at the physician’s discretion (n = 1).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.
Similar content being viewed by others
References
R Sposto IJ Ertel RD Jenkin CP Boesel JL Venes JA Ortega AE Evans W Wara D Hammond (1989) ArticleTitleThe effectiveness of chemotherapy for treatment of high grade astrocytoma in children: results of a randomized trial. A report from the Childrens Cancer Study Group J Neuro-oncol 7 165–177 Occurrence Handle1:STN:280:BiaA1c7nvFw%3D
JL Finlay JM Boyett AJ Yates JH Wisoff JM Milstein JR Geyer SJ Bertolone P McGuire JM Cherlow M Tefft et al. (1995) ArticleTitleRandomized phase III trial in childhood high-grade astrocytoma comparing vincristine, lomustine, and prednisone with the eight-drugs-in-1-day regimen. Children’s Cancer Group J Clin Oncol 13 112–123 Occurrence Handle1:STN:280:ByqD1MnptlI%3D Occurrence Handle7799011
JE Wolff G Molenkamp S Westphal T Pietsch A Gnekow RD Kortmann J Kuehl (2000) ArticleTitleOral trofosfamide and etoposide in pediatric patients with glioblastoma multiforme Cancer 89 2131–2137 Occurrence Handle10.1002/1097-0142(20001115)89:10<2131::AID-CNCR14>3.0.CO;2-J Occurrence Handle1:CAS:528:DC%2BD3cXotlymtrk%3D Occurrence Handle11066055
JE Wolff AK Gnekow RD Kortmann T Pietsch C Urban N Graf J Kuhl (2002) ArticleTitlePreradiation chemotherapy for pediatric patients with high-grade glioma Cancer 94 264–271 Occurrence Handle10.1002/cncr.10114 Occurrence Handle1:CAS:528:DC%2BD38XlslKntw%3D%3D Occurrence Handle11815986
M Massimino L Gandola R Luksch F Spreafico D Riva C Solero F Giangaspero F Locatelli M Podda F Bozzi E Pignoli P Collini G Cefalo M Zecca M Casanova A Ferrari M Terenziani C Meazza D Polastri D Scaramuzza F Ravagnani F Fossati-Bellani (2005) ArticleTitleSequential chemotherapy, high-dose thiotepa, circulating progenitor cell rescue, and radiotherapy for childhood high-grade glioma Neuro-oncol 7 41–48 Occurrence Handle10.1215/S1152851704000304 Occurrence Handle1:CAS:528:DC%2BD2MXhvFyrtrw%3D Occurrence Handle15701281
HS Friedman RE McLendon T Kerby M Dugan SH Bigner AJ Henry DM Ashley J Krischer S Lovell K Rasheed F Marchev AJ Seman I Cokgor J Rich E Stewart OM Colvin JM Provenzale DD Bigner MM Haglund AH Friedman PL Modrich (1998) ArticleTitleDNA mismatch repair and O6-alkylguanine-DNA alkyltransferase analysis and response to Temodal in newly diagnosed malignant glioma J Clin Oncol 16 3851–3857 Occurrence Handle1:CAS:528:DyaK1MXos1Si Occurrence Handle9850030
WK Yung MD Prados R Yaya-Tur SS Rosenfeld M Brada HS Friedman R Albright J Olson SM Chang AM O’Neill AH Friedman J Bruner N Yue M Dugan S Zaknoen VA Levin (1999) ArticleTitleMulticenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. Temodal Brain Tumor Group J Clin Oncol 17 2762–2771 Occurrence Handle1:CAS:528:DyaK1MXmtlWru7s%3D Occurrence Handle10561351
WK Yung RE Albright J Olson R Fredericks K Fink MD Prados M Brada A Spence RJ Hohl W Shapiro M Glantz H Greenberg RG Selker NA Vick R Rampling H Friedman P Phillips J Bruner N Yue D Osoba S Zaknoen VA Levin (2000) ArticleTitleA phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse Br J Cancer 83 588–593 Occurrence Handle10.1054/bjoc.2000.1316 Occurrence Handle1:CAS:528:DC%2BD3cXmvVCgsrs%3D Occurrence Handle10944597
M Brada K Hoang-Xuan R Rampling PY Dietrich LY Dirix D Macdonald JJ Heimans BA Zonnenberg JM Bravo-Marques R Henriksson R Stupp N Yue J Bruner M Dugan S Rao S Zaknoen (2001) ArticleTitleMulticenter phase II trial of temozolomide in patients with glioblastoma multiforme at first relapse Ann Oncol 12 259–266 Occurrence Handle10.1023/A:1008382516636 Occurrence Handle1:STN:280:DC%2BD3M3gvFamtg%3D%3D Occurrence Handle11300335
EJ Estlin L Lashford S Ablett L Price R Gowing A Gholkar J Kohler IJ Lewis B Morland CR Pinkerton MC Stevens M Mott R Stevens DR Newell D Walker C Dicks-Mireaux H McDowell P Reidenberg P Statkevich A Marco V Batra M Dugan AD Pearson (1998) ArticleTitlePhase I study of temozolomide in paediatric patients with advanced cancer United Kingdom Children’s Cancer Study Group Br J Cancer 78 652–661 Occurrence Handle1:CAS:528:DyaK1cXlvVCgs7k%3D Occurrence Handle9744506
HS Nicholson M Krailo MM Ames NL Seibel JM Reid W Liu-Mares LG Vezina AG Ettinger GH Reaman (1998) ArticleTitlePhase I study of temozolomide in children and adolescents with recurrent solid tumors: a report from the Children’s Cancer Group J Clin Oncol 16 3037–3043 Occurrence Handle1:CAS:528:DyaK1cXmtFSlsLo%3D Occurrence Handle9738573
A Broniscer L Iacono M Chintagumpala M Fouladi D Wallace DC Bowers C Stewart MJ Krasin A Gajjar (2005) ArticleTitleRole of temozolomide after radiotherapy for newly diagnosed diffuse brainstem glioma in children: Results of a multiinstitutional study (SJHG-98) Cancer 103 133–139 Occurrence Handle10.1002/cncr.20741 Occurrence Handle1:CAS:528:DC%2BD2MXmtVartw%3D%3D Occurrence Handle15565574
JC Panetta MN Kirstein A Gajjar G Nair M Fouladi RL Heideman M Wilkinson CF Stewart (2003) ArticleTitlePopulation pharmacokinetics of temozolomide and metabolites in infants and children with primary central nervous system tumors Cancer Chemother Pharmacol 52 435–441 Occurrence Handle10.1007/s00280-003-0670-4 Occurrence Handle1:CAS:528:DC%2BD3sXovVKntbw%3D Occurrence Handle13680158
EL Kaplan P Meier (1958) ArticleTitleNonparametric estimation from incomplete observations J Am Stat Assoc 53 457–481
R Peto MC Pike P Armitage NE Breslow DR Cox SV Howard N Mantel K McPherson J Peto PG Smith (1976) ArticleTitleDesign and analysis of randomized clinical trials requiring prolonged observation of each patient. I. Introduction and design Br J Cancer 34 585–612 Occurrence Handle1:STN:280:CSiD1cjlsVU%3D Occurrence Handle795448
J Wyatt-Ashmead BK Kleinschmidt-DeMasters DA Hill GW Mierau L McGavran SJ Thompson NK Foreman (2001) ArticleTitleRhabdoid glioblastoma Clin Neuropathol 20 248–255 Occurrence Handle1:STN:280:DC%2BD38%2FjtFGhsA%3D%3D Occurrence Handle11758780
JW Campbell IF Pollack AJ Martinez B Shultz (1996) ArticleTitleHigh-grade astrocytomas in children: radiologically complete resection is associated with an excellent long-term prognosis Neurosurgery 38 258–264 Occurrence Handle1:STN:280:ByiD383mvFY%3D Occurrence Handle8869052
MK Bucci A Maity AJ Janss JB Belasco MJ Fisher ZA Tochner L Rorke LN Sutton PC Phillips HK Shu (2004) ArticleTitleNear complete surgical resection predicts a favorable outcome in pediatric patients with nonbrainstem, malignant gliomas: results from a single center in the magnetic resonance imaging era Cancer 101 817–824 Occurrence Handle10.1002/cncr.20422 Occurrence Handle15305415
IF Pollack JM Boyett AJ Yates PC Burger FH Gilles RL Davis JL Finlay InstitutionalAuthorNameChildren’s Cancer Group (2003) ArticleTitleThe influence of central review on outcome associations in childhood malignant gliomas: results from the CCG-945 experience Neuro-oncol 5 197–207 Occurrence Handle10.1215/S1152851703000097 Occurrence Handle12816726
MR Gilbert HS Friedman JF Kuttesch MD Prados JJ Olson GH Reaman SL Zaknoen (2002) ArticleTitleA phase II study of temozolomide in patients with newly diagnosed supratentorial malignant glioma before radiation therapy Neuro-oncol 4 261–267 Occurrence Handle10.1215/15228517-4-4-261 Occurrence Handle1:CAS:528:DC%2BD38XotVSmt7Y%3D Occurrence Handle12356356
R Stupp WP Mason MJ Bent Particlevan Den M Weller B Fisher MJ Taphoorn K Belanger AA Brandes C Marosi U Bogdahn J Curschmann RC Janzer SK Ludwin T Gorlia A Allgeier D Lacombe JG Cairncross E Eisenhauer RO Mirimanoff (2005) ArticleTitleRadiotherapy plus concomitant and adjuvant temozolomide for glioblastoma N Engl J Med 352 987–996 Occurrence Handle10.1056/NEJMoa043330 Occurrence Handle1:CAS:528:DC%2BD2MXit1Wksbk%3D Occurrence Handle15758009
ME Hegi AC Diserens T Gorlia MF Hamou N Tribolet Particlede M Weller JM Kros JA Hainfellner W Mason L Mariani JE Bromberg P Hau RO Mirimanoff JG Cairncross RC Janzer R Stupp (2005) ArticleTitleMGMT gene silencing and benefit from temozolomide in glioblastoma N Engl J Med 352 997–1003 Occurrence Handle10.1056/NEJMoa043331 Occurrence Handle1:CAS:528:DC%2BD2MXit1Wktro%3D Occurrence Handle15758010
LS Lashford P Thiesse A Jouvet T Jaspan D Couanet PD Griffiths F Doz J Ironside K Robson R Hobson M Dugan AD Pearson G Vassal D Frappaz (2002) ArticleTitleA United Kingdom Children’s Cancer Study Group, French Society for Pediatric Oncology Intergroup Study: Temozolomide in malignant gliomas of childhood: a United Kingdom Children’s Cancer Study Group and French Society for Pediatric Oncology Intergroup Study J Clin Oncol 20 4684–4691 Occurrence Handle10.1200/JCO.2002.08.141 Occurrence Handle1:CAS:528:DC%2BD38XptlGiu7k%3D Occurrence Handle12488414
AC Verschuur J Grill A Lelouch-Tubiana D Couanet C Kalifa G Vassal (2004) ArticleTitleTemozolomide in paediatric high-grade glioma: a key for combination therapy? Br J Cancer 91 425–429 Occurrence Handle10.1038/sj.bjc.6601997 Occurrence Handle1:CAS:528:DC%2BD2cXlvF2ltrw%3D Occurrence Handle15266331
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Broniscer, A., Chintagumpala, M., Fouladi, M. et al. Temozolomide after Radiotherapy for Newly Diagnosed High-grade Glioma and Unfavorable Low-grade Glioma in Children. J Neurooncol 76, 313–319 (2006). https://doi.org/10.1007/s11060-005-7409-5
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11060-005-7409-5