Journal of Neuro-Oncology

, Volume 100, Issue 2, pp 193–198 | Cite as

A prospective study of temozolomide plus thalidomide during and after radiation therapy for pediatric diffuse pontine gliomas: preliminary results of the Korean Society for Pediatric Neuro-Oncology study

  • Chae-Yong Kim
  • Seung-Ki Kim
  • Ji Hoon Phi
  • Min Mi Lee
  • In Ah Kim
  • Il Han Kim
  • Kyu-Chang Wang
  • Hye-Lim Jung
  • Mee Jeong Lee
  • Byung-Kyu Cho
Clinical Study - Patient Study


This prospective study was performed to determine the efficacy and safety of temozolomide (TMZ) plus thalidomide during and after radiation therapy (RT) in pediatric patients with newly diagnosed diffuse pontine glioma (DPG). Seventeen patients with pediatric DPG were enrolled between November 2004 and March 2008. The median age was eight years (range, 3–16 years); seven patients were male and ten were female. With the exception of one glioblastoma case, which was diagnosed via open biopsy, all diagnoses were established using neuroradiological studies. The authors used the Korean Society for Pediatric Neuro-Oncology (KSPNO)-A053 protocol. The mean follow-up period was 12 months (range, 8.5–25 months). Five patients were withdrawn from the study. The rates of response to treatment and survival were analyzed in 12 patients. Ten out of the 12 patients showed a partial response (PR), whereas one patient exhibited stable disease (SD) and another patient had progressive disease (PD). The tumor control rate was 92% (11/12) and the response rate was 83% (10/12). The median progression-free survival (PFS) of the 12 patients was 7.2 months (95% confidence interval (CI), 3.6–10.7). Six-month and twelve-month PFS were 58.3 and 16.7%, respectively. Overall survival (OS) was 12.7 months (95% CI, 10.4–15.1). One and two-year survival were 58.3 and 25%, respectively. The main adverse effect was hematological toxicity, with four patients exhibiting grade 3 or 4 toxicity. All patients tolerated the regimen well enough to continue the adjuvant chemotherapy. No Pneumocystis jiroveci pneumonia was noted. The TMZ plus thalidomide regimen was safe and tolerated well enough to be administered on an outpatient basis. Larger studies are required to demonstrate the efficacy of this regimen.


Brainstem tumor Pontine tumor Concomitant chemoradiotherapy Temozolomide Thalidomide 



This study was supported by a grant from the National Research and Development Program for Cancer Control, Ministry of Health, Welfare and Family Affairs, Republic of Korea (grant no. 0520300 (B–K Cho)), and by a Korean Science and Engineering Foundation (KOSEF) grant funded by the Korean Government (MEST; grant no. R01-2008-000-20268-0 (S–K Kim)).


  1. 1.
    Broniscer A, Laningham FH, Sanders RP et al (2008) Young age may predict a better outcome for children with diffuse pontine glioma. Cancer 113:566–572CrossRefPubMedGoogle Scholar
  2. 2.
    Bouffet E, Raquin M, Doz F et al (2000) Radiotherapy followed by high dose busulfan and thiotepa: a prospective assessment of high dose chemotherapy in children with diffuse pontine gliomas. Cancer 88:685–692CrossRefPubMedGoogle Scholar
  3. 3.
    Dunkel IJ, Garvin JH Jr, Goldman S (1998) High dose chemotherapy with autologous bone marrow rescue for children with diffuse pontine brain stem tumors. Children’s Cancer Group. J Neurooncol 37:67–73CrossRefPubMedGoogle Scholar
  4. 4.
    Finlay JL, Zacharoulis S (2005) The treatment of high grade gliomas and diffuse intrinsic pontine tumors of childhood and adolescence: a historic—and futuristic—perspective. J Neurooncol 75:253–266CrossRefPubMedGoogle Scholar
  5. 5.
    Frazier JL, Lee J, Thomale UW et al (2009) Treatment of diffuse intrinsic brainstem gliomas: failed approaches and future strategies. J Neurosurg Pediatr 4:259–269CrossRefGoogle Scholar
  6. 6.
    Grill J, Bhangoo R (2007) Recent development in chemotherapy of paediatric brain tumours. Curr Opin Oncol 19:612–615CrossRefPubMedGoogle Scholar
  7. 7.
    Jennings MT, Sposto R, Boyett JM et al (2002) Preradiation chemotherapy in primary high-risk brainstem tumors: phase II study CCG-9941 of the Children’s Cancer Group. J Clin Oncol 20:3431–3437CrossRefPubMedGoogle Scholar
  8. 8.
    Korones DN, Fisher PG, Kretschmar C et al (2008) Treatment of children with diffuse intrinsic brain stem glioma with radiotherapy, vincristine and oral VP-16: a Children’s Oncology Group phase II study. Pediatr Blood Cancer 50(2):227–230CrossRefPubMedGoogle Scholar
  9. 9.
    Kretschmar CS, Tarbell NJ, Barnes PD et al (1993) Pre-irradiation chemotherapy and hyperfractionated radiation therapy 66 Gy for children with brain stem tumors. A phase II study of the Pediatric Oncology Group, Protocol 8833. Cancer 72:1404–1413CrossRefPubMedGoogle Scholar
  10. 10.
    Hargrave D, Chuang N, Bouffet E (2008) Conventional MRI cannot predict survival in childhood diffuse intrinsic pontine glioma. J Neurooncol 86:313–319CrossRefPubMedGoogle Scholar
  11. 11.
    Leach PA, Estlin EJ, Coope DJ et al (2008) Diffuse brainstem gliomas in children: should we or shouldn’t we biopsy? Br J Neurosurg 22:619–624CrossRefPubMedGoogle Scholar
  12. 12.
    Massimino M, Spreafico F, Biassoni V et al (2008) Diffuse pontine gliomas in children: changing strategies, changing results? A mono-institutional 20-year experience. J Neurooncol 87:355–361CrossRefPubMedGoogle Scholar
  13. 13.
    Qaddoumi I, Ezam N, Swaidan M et al (2009) Diffuse pontine glioma in Jordan and impact of up-front prognosis disclosure with parents and families. J Child Neurol 24:460–465CrossRefPubMedGoogle Scholar
  14. 14.
    Rutka JT, Kuo JS, Carter M et al (2004) Advances in the treatment of pediatric brain tumors. Expert Rev Neurother 4:879–893CrossRefPubMedGoogle Scholar
  15. 15.
    Roujeau T, Machado G, Garnett MR et al (2007) Stereotactic biopsy of diffuse pontine lesions in children. J Neurosurg 107(1):1–4CrossRefPubMedGoogle Scholar
  16. 16.
    Janssens GO, Gidding CE, Van Lindert EJ et al (2009) The role of hypofractionation radiotherapy for diffuse intrinsic brainstem glioma in children: a pilot study. Int J Radiat Oncol Biol Phys 73:722–726PubMedGoogle Scholar
  17. 17.
    Marcus KJ, Dutton SC, Barnes P et al (2003) A phase I trial of etanidazole and hyperfractionated radiotherapy in children with diffuse brainstem glioma. Int J Radiat Oncol Biol Phys 55:1182–1185PubMedGoogle Scholar
  18. 18.
    Postovsky S, Eran A, Weyl Ben Arush M (2008) Unusual case of leptomeningeal dissemination of a diffuse pontine high-grade astrocytoma in a child. Pediatr Neurosurg 44:208–211CrossRefPubMedGoogle Scholar
  19. 19.
    Sirachainan N, Pakakasama S, Visudithbhan A et al (2008) Concurrent radiotherapy with temozolomide followed by adjuvant temozolomide and cis-retinoic acid in children with diffuse intrinsic pontine glioma. Neuro Oncol 10:577–582CrossRefPubMedGoogle Scholar
  20. 20.
    Turner CD, Chi S, Marcus KJ et al (2007) Phase II study of thalidomide and radiation in children with newly diagnosed brain stem gliomas and glioblastoma multiforme. J Neurooncol 82:95–101CrossRefPubMedGoogle Scholar
  21. 21.
    Turner CD, Gururangan S, Eastwood J et al (2002) Phase II study of irinotecan (CPT-11) in children with high-risk malignant brain tumors: the Duke experience. Neuro Oncol 4:102–108PubMedGoogle Scholar
  22. 22.
    Wolff JE, Westphal S, Mölenkamp G et al (2002) Treatment of paediatric pontine glioma with oral trophosphamide and etoposide. Br J Cancer 87:945–949CrossRefPubMedGoogle Scholar
  23. 23.
    Stupp R, Dietrich PY, Ostermann Kraljevic S et al (2002) Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide. J Clin Oncol 20:1375–1382CrossRefPubMedGoogle Scholar
  24. 24.
    Stupp R, Mason WP, van den Bent MJ et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996CrossRefPubMedGoogle Scholar
  25. 25.
    Perry J, Laperriere N, Zuraw L et al (2007) Adjuvant chemotherapy for adults with malignant glioma: a systematic review. Can J Neurol Sci 34:402–410PubMedGoogle Scholar
  26. 26.
    Choi JW, Lee MM, Kim IA et al (2008) The outcomes of concomitant chemoradiotherapy followed by adjuvant chemotherapy with temozolomide for newly diagnosed high grade gliomas: the preliminary results of single center prospective study. J Korean Neurosurg Soc 44:222–227CrossRefPubMedGoogle Scholar
  27. 27.
    Kocher M, Kunze S, Elch HT et al (2005) Efficacy and toxicity of postoperative temozolomide radiochemotherapy in malignant glioma. Strahlenther Onkol 18:157–163CrossRefGoogle Scholar
  28. 28.
    Atkins MB, Sosman JA, Agarwala S et al (2008) Temozolomide, thalidomide, and whole brain radiation therapy for patients with brain metastasis from metastatic melanoma: a phase II Cytokine Working Group study. Cancer 113:2139–2145CrossRefPubMedGoogle Scholar
  29. 29.
    Chang SM, Lamborn KR, Malec M et al (2004) Phase II study of temozolomide and thalidomide with radiation therapy for newly diagnoses glioblastoma multiforme. Int J Radiat Oncol Biol Phys 60:353–357PubMedGoogle Scholar
  30. 30.
    Kesari S, Schiff D, Henson JW et al (2008) Phase II study of temozolomide, thalidomide, and celecoxib for newly diagnosed glioblastoma in adults. Neuro Oncol 10:300–308CrossRefPubMedGoogle Scholar
  31. 31.
    Broniscer A, Iacono L, Chintagumpala M et al (2005) Role of temozolomide after radiotherapy for newly diagnosed diffuse brainstem glioma in children: results of a multiinstitutional study (SJHG-98). Cancer 103:133–139CrossRefPubMedGoogle Scholar
  32. 32.
    Puduvalli VK, Giglio P, Groves MD et al (2008) Phase II trial of irinotecan and thalidomide in adults with recurrent glioblastoma multiforme. Neuro Oncol 10:216–222CrossRefPubMedGoogle Scholar
  33. 33.
    Knisely JP, Berkey B, Chakravarti A et al (2008) A phase III study of conventional radiation therapy plus thalidomide versus conventional radiation therapy for multiple brain metastases (RTOG 0118). Int J Radiat Oncol Biol Phys 71:79–86PubMedGoogle Scholar
  34. 34.
    Wagner S, Warmuth-Metz M, Emser A et al (2006) Treatment options in childhood pontine gliomas. J Neurooncol 79:281–287CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Chae-Yong Kim
    • 1
    • 5
  • Seung-Ki Kim
    • 2
    • 5
  • Ji Hoon Phi
    • 2
    • 5
  • Min Mi Lee
    • 1
    • 5
  • In Ah Kim
    • 3
    • 5
  • Il Han Kim
    • 4
    • 5
  • Kyu-Chang Wang
    • 2
    • 5
  • Hye-Lim Jung
    • 6
  • Mee Jeong Lee
    • 7
  • Byung-Kyu Cho
    • 2
    • 5
  1. 1.Department of NeurosurgerySeoul National University Bundang HospitalSeongnam-siKorea
  2. 2.Division of Pediatric NeurosurgerySeoul National University Children’s HospitalSeoulSouth Korea
  3. 3.Department of Radiation OncologySeoul National University Bundang HospitalSeongnam-siKorea
  4. 4.Department of Radiation OncologySeoul National University HospitalSeoulKorea
  5. 5.Seoul National University College of MedicineSeoulKorea
  6. 6.Department of PediatricsSungkyunkwan University Kangbuk Samsung HospitalSeoulKorea
  7. 7.Department of PediatricsDankook University College of MedicineCheonanKorea

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