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Journal of Neuro-Oncology

, Volume 76, Issue 3, pp 313–319 | Cite as

Temozolomide after Radiotherapy for Newly Diagnosed High-grade Glioma and Unfavorable Low-grade Glioma in Children

  • Alberto BroniscerEmail author
  • Murali Chintagumpala
  • Maryam Fouladi
  • Matthew J. Krasin
  • Mehmet Kocak
  • Daniel C. Bowers
  • Lisa C. Iacono
  • Thomas E. Merchant
  • Clinton F. Stewart
  • Peter J. Houghton
  • Larry E. Kun
  • Davonna Ledet
  • Amar Gajjar
Article

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 Four patients did not receive radiotherapy in this study because of consent withdrawn (n = 2), toxicity during window therapy (n = 1), or at the physician’s discretion (n = 1).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.

Keywords

bithalamic children glioma gliomatosis cerebri high-grade radiotherapy temozolomide 

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References

  1. 1.
    Sposto, R, Ertel, IJ, Jenkin, RD, Boesel, CP, Venes, JL, Ortega, JA, Evans, AE, Wara, W, Hammond, D 1989The effectiveness of chemotherapy for treatment of high grade astrocytoma in children: results of a randomized trial. A report from the Childrens Cancer Study GroupJ Neuro-oncol7165177Google Scholar
  2. 2.
    Finlay, JL, Boyett, JM, Yates, AJ, Wisoff, JH, Milstein, JM, Geyer, JR, Bertolone, SJ, McGuire, P, Cherlow, JM, Tefft, M,  et al. 1995Randomized phase III trial in childhood high-grade astrocytoma comparing vincristine, lomustine, and prednisone with the eight-drugs-in-1-day regimen. Children’s Cancer GroupJ Clin Oncol13112123PubMedGoogle Scholar
  3. 3.
    Wolff, JE, Molenkamp, G, Westphal, S, Pietsch, T, Gnekow, A, Kortmann, RD, Kuehl, J 2000Oral trofosfamide and etoposide in pediatric patients with glioblastoma multiformeCancer8921312137CrossRefPubMedGoogle Scholar
  4. 4.
    Wolff, JE, Gnekow, AK, Kortmann, RD, Pietsch, T, Urban, C, Graf, N, Kuhl, J 2002Preradiation chemotherapy for pediatric patients with high-grade gliomaCancer94264271CrossRefPubMedGoogle Scholar
  5. 5.
    Massimino, M, Gandola, L, Luksch, R, Spreafico, F, Riva, D, Solero, C, Giangaspero, F, Locatelli, F, Podda, M, Bozzi, F, Pignoli, E, Collini, P, Cefalo, G, Zecca, M, Casanova, M, Ferrari, A, Terenziani, M, Meazza, C, Polastri, D, Scaramuzza, D, Ravagnani, F, Fossati-Bellani, F 2005Sequential chemotherapy, high-dose thiotepa, circulating progenitor cell rescue, and radiotherapy for childhood high-grade gliomaNeuro-oncol74148CrossRefPubMedGoogle Scholar
  6. 6.
    Friedman, HS, McLendon, RE, Kerby, T, Dugan, M, Bigner, SH, Henry, AJ, Ashley, DM, Krischer, J, Lovell, S, Rasheed, K, Marchev, F, Seman, AJ, Cokgor, I, Rich, J, Stewart, E, Colvin, OM, Provenzale, JM, Bigner, DD, Haglund, MM, Friedman, AH, Modrich, PL 1998DNA mismatch repair and O6-alkylguanine-DNA alkyltransferase analysis and response to Temodal in newly diagnosed malignant gliomaJ Clin Oncol1638513857PubMedGoogle Scholar
  7. 7.
    Yung, WK, Prados, MD, Yaya-Tur, R, Rosenfeld, SS, Brada, M, Friedman, HS, Albright, R, Olson, J, Chang, SM, O’Neill, AM, Friedman, AH, Bruner, J, Yue, N, Dugan, M, Zaknoen, S, Levin, VA 1999Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. Temodal Brain Tumor GroupJ Clin Oncol1727622771PubMedGoogle Scholar
  8. 8.
    Yung, WK, Albright, RE, Olson, J, Fredericks, R, Fink, K, Prados, MD, Brada, M, Spence, A, Hohl, RJ, Shapiro, W, Glantz, M, Greenberg, H, Selker, RG, Vick, NA, Rampling, R, Friedman, H, Phillips, P, Bruner, J, Yue, N, Osoba, D, Zaknoen, S, Levin, VA 2000A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapseBr J Cancer83588593CrossRefPubMedGoogle Scholar
  9. 9.
    Brada, M, Hoang-Xuan, K, Rampling, R, Dietrich, PY, Dirix, LY, Macdonald, D, Heimans, JJ, Zonnenberg, BA, Bravo-Marques, JM, Henriksson, R, Stupp, R, Yue, N, Bruner, J, Dugan, M, Rao, S, Zaknoen, S 2001Multicenter phase II trial of temozolomide in patients with glioblastoma multiforme at first relapseAnn Oncol12259266CrossRefPubMedGoogle Scholar
  10. 10.
    Estlin, EJ, Lashford, L, Ablett, S, Price, L, Gowing, R, Gholkar, A, Kohler, J, Lewis, IJ, Morland, B, Pinkerton, CR, Stevens, MC, Mott, M, Stevens, R, Newell, DR, Walker, D, Dicks-Mireaux, C, McDowell, H, Reidenberg, P, Statkevich, P, Marco, A, Batra, V, Dugan, M, Pearson, AD 1998Phase I study of temozolomide in paediatric patients with advanced cancer United Kingdom Children’s Cancer Study GroupBr J Cancer78652661PubMedGoogle Scholar
  11. 11.
    Nicholson, HS, Krailo, M, Ames, MM, Seibel, NL, Reid, JM, Liu-Mares, W, Vezina, LG, Ettinger, AG, Reaman, GH 1998Phase I study of temozolomide in children and adolescents with recurrent solid tumors: a report from the Children’s Cancer GroupJ Clin Oncol1630373043PubMedGoogle Scholar
  12. 12.
    Broniscer, A, Iacono, L, Chintagumpala, M, Fouladi, M, Wallace, D, Bowers, DC, Stewart, C, Krasin, MJ, Gajjar, A 2005Role of temozolomide after radiotherapy for newly diagnosed diffuse brainstem glioma in children: Results of a multiinstitutional study (SJHG-98)Cancer103133139CrossRefPubMedGoogle Scholar
  13. 13.
    Panetta, JC, Kirstein, MN, Gajjar, A, Nair, G, Fouladi, M, Heideman, RL, Wilkinson, M, Stewart, CF 2003Population pharmacokinetics of temozolomide and metabolites in infants and children with primary central nervous system tumorsCancer Chemother Pharmacol52435441CrossRefPubMedGoogle Scholar
  14. 14.
    Kaplan, EL, Meier, P 1958Nonparametric estimation from incomplete observationsJ Am Stat Assoc53457481Google Scholar
  15. 15.
    Peto, R, Pike, MC, Armitage, P, Breslow, NE, Cox, DR, Howard, SV, Mantel, N, McPherson, K, Peto, J, Smith, PG 1976Design and analysis of randomized clinical trials requiring prolonged observation of each patient. I. Introduction and designBr J Cancer34585612PubMedGoogle Scholar
  16. 16.
    Wyatt-Ashmead, J, Kleinschmidt-DeMasters, BK, Hill, DA, Mierau, GW, McGavran, L, Thompson, SJ, Foreman, NK 2001Rhabdoid glioblastomaClin Neuropathol20248255PubMedGoogle Scholar
  17. 17.
    Campbell, JW, Pollack, IF, Martinez, AJ, Shultz, B 1996High-grade astrocytomas in children: radiologically complete resection is associated with an excellent long-term prognosisNeurosurgery38258264PubMedGoogle Scholar
  18. 18.
    Bucci, MK, Maity, A, Janss, AJ, Belasco, JB, Fisher, MJ, Tochner, ZA, Rorke, L, Sutton, LN, Phillips, PC, Shu, HK 2004Near complete surgical resection predicts a favorable outcome in pediatric patients with nonbrainstem, malignant gliomas: results from a single center in the magnetic resonance imaging eraCancer101817824CrossRefPubMedGoogle Scholar
  19. 19.
    Pollack, IF Boyett, JM Yates, AJ Burger, PC Gilles, FH Davis, RL Finlay, JL Children’s Cancer Group2003The influence of central review on outcome associations in childhood malignant gliomas: results from the CCG-945 experienceNeuro-oncol5197207CrossRefPubMedGoogle Scholar
  20. 20.
    Gilbert, MR, Friedman, HS, Kuttesch, JF, Prados, MD, Olson, JJ, Reaman, GH, Zaknoen, SL 2002A phase II study of temozolomide in patients with newly diagnosed supratentorial malignant glioma before radiation therapyNeuro-oncol4261267CrossRefPubMedGoogle Scholar
  21. 21.
    Stupp, R, Mason, WP, Bent, MJ, Weller, M, Fisher, B, Taphoorn, MJ, Belanger, K, Brandes, AA, Marosi, C, Bogdahn, U, Curschmann, J, Janzer, RC, Ludwin, SK, Gorlia, T, Allgeier, A, Lacombe, D, Cairncross, JG, Eisenhauer, E, Mirimanoff, RO 2005Radiotherapy plus concomitant and adjuvant temozolomide for glioblastomaN Engl J Med352987996CrossRefPubMedGoogle Scholar
  22. 22.
    Hegi, ME, Diserens, AC, Gorlia, T, Hamou, MF, Tribolet, N, Weller, M, Kros, JM, Hainfellner, JA, Mason, W, Mariani, L, Bromberg, JE, Hau, P, Mirimanoff, RO, Cairncross, JG, Janzer, RC, Stupp, R 2005MGMT gene silencing and benefit from temozolomide in glioblastomaN Engl J Med3529971003CrossRefPubMedGoogle Scholar
  23. 23.
    Lashford, LS, Thiesse, P, Jouvet, A, Jaspan, T, Couanet, D, Griffiths, PD, Doz, F, Ironside, J, Robson, K, Hobson, R, Dugan, M, Pearson, AD, Vassal, G, Frappaz, D 2002A 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 StudyJ Clin Oncol2046844691CrossRefPubMedGoogle Scholar
  24. 24.
    Verschuur, AC, Grill, J, Lelouch-Tubiana, A, Couanet, D, Kalifa, C, Vassal, G 2004Temozolomide in paediatric high-grade glioma: a key for combination therapy?Br J Cancer91425429CrossRefPubMedGoogle Scholar

Copyright information

© Springer 2005

Authors and Affiliations

  • Alberto Broniscer
    • 1
    Email author
  • Murali Chintagumpala
    • 2
  • Maryam Fouladi
    • 1
  • Matthew J. Krasin
    • 3
  • Mehmet Kocak
    • 4
  • Daniel C. Bowers
    • 5
  • Lisa C. Iacono
    • 6
  • Thomas E. Merchant
    • 3
  • Clinton F. Stewart
    • 6
  • Peter J. Houghton
    • 7
  • Larry E. Kun
    • 3
  • Davonna Ledet
    • 1
  • Amar Gajjar
    • 1
  1. 1.Department of Hematology-OncologySt. Jude Children’s Research HospitalMemphisUSA
  2. 2.Department of Pediatric Hematology-OncologyTexas Children’s HospitalHoustonUSA
  3. 3.Department of Radiological SciencesSt. Jude Children’s Research HospitalMemphisUSA
  4. 4.Department of BiostatisticsSt. Jude Children’s Research HospitalMemphisUSA
  5. 5.Department of PediatricsUniversity of Texas Southwestern Medical Center at DallasDallasUSA
  6. 6.Department of Pharmaceutical SciencesSt. Jude Children’s Research HospitalMemphisUSA
  7. 7.Department of Molecular PharmacologySt. Jude Children’s Research HospitalMemphisUSA

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