Chemotherapy

Abstract

Chemotherapy is effective in the treatment of many pediatric brain tumors. It offers benefits such as stabilizing disease, reducing radiation dose as well as delaying or eliminating the need for radiation therapy. For several tumor types, chemotherapy has shown improved survival. Agents used in pediatric brain tumors include alkylators, topoisomerase inhibitors, antimetabolites, and plant alkaloids. Temozolomide and bevacizumab are among emerging new therapies that have shown encouraging preliminary results and are being further researched. The clinical use and acute toxicities of commonly used chemotherapy agents are discussed. Finally, intrathecal and intra-Ommaya therapies aimed at overcoming the blood–brain barrier are reviewed.

Keywords

Chemotherapy Acute toxicities Mode of delivery Blood–brain barrier 

References

  1. 1.
    Jakacki RI, Burger PC, Zhou T, Holmes EJ, Kocak M, Onar A, et al. Outcome of children with metastatic medulloblastoma treated with carboplatin during craniospinal radiotherapy: a Children’s Oncology Group phase I/II study. J Clin Oncol. 2012;30:2648–53.CrossRefPubMedGoogle Scholar
  2. 2.
    Gajjar A, Chintagumpala M, Ashley D, Kellie D, Kun LE, Merchant TE, et al. Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial. Lancet Oncol. 2006;7:813–20.CrossRefPubMedGoogle Scholar
  3. 3.
    Wolff JE, Driever PH, Erdlenbruch B, Kortmann RD, Rutkowski S, Pietsch T, et al. Intensive chemotherapy improves survival in pediatric high-grade glioma after gross total resection: results of the HIT-gBM-c protocol. Cancer. 2010;116:705–12.CrossRefPubMedGoogle Scholar
  4. 4.
    Chintagumpala MM, Friedman HS, Stewart CF, Kepner J, McLendon RE, Modrich PL, et al. A phase II window trial of procarbazine and topotecan in children with high-grade glioma: a report from the children’s oncology group. J Neurooncol. 2006;77: 193–8.CrossRefPubMedGoogle Scholar
  5. 5.
    Cohen KJ, Pollack IF, Zhou T, Buxton A, Holmes EJ, Burger PC, et al. Temozolomide in the treatment of high-grade gliomas in children: a report from the Children’s Oncology Group. Neuro Oncol. 2011;13: 317–23.CrossRefPubMedCentralPubMedGoogle Scholar
  6. 6.
    Cohen KJ, Heideman RL, Zhou T, Holmes EJ, Lavey RS, Bouffet E, Pollack IF. Temozolomide in the treatment of children with newly diagnosed diffuse intrinsic pontine gliomas: a report from the Children’s Oncology Group. Neuro Oncol. 2011;13: 410–6.CrossRefPubMedCentralPubMedGoogle Scholar
  7. 7.
    Gururangan S, Fisher MJ, Allen JC, Herndon II JE, Quinn JA, Reardon DA, et al. Temozolomide in children with progressive low-grade glioma. Neuro Oncol. 2007;9:161–8.CrossRefPubMedCentralPubMedGoogle Scholar
  8. 8.
    Lashford LS, Theisse P, Jouvet A, Jaspan T, Couanet D, Griffiths PD, et al. 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. 2002;20: 4684–91.CrossRefPubMedGoogle Scholar
  9. 9.
    Gottardo NG, Gajjar A. Chemotherapy for malignant brain tumours of childhood. J Child Neurol. 2008; 23:1149–59.CrossRefPubMedCentralPubMedGoogle Scholar
  10. 10.
    Ashley DM, Meier L, Kerby T, Zalduondo FM, Friedman HS, Gajjar A, et al. Response of recurrent medulloblastoma to low-dose oral etoposide. J Clin Oncol. 1996;14:1922–7.PubMedGoogle Scholar
  11. 11.
    Sandri A, Massimino M, Mastrodicasa L, Sardi N, Bertin D, Basso ME, et al. Treatment with oral etoposide for childhood recurrent ependymomas. J Pediatr Hematol Oncol. 2005;27:486–90.CrossRefPubMedGoogle Scholar
  12. 12.
    Korones DN, Fisher PG, Kretschmar C, Zhou T, Chen Z, Kepner J, Freeman C. 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. 2008; 50:227–30.CrossRefPubMedGoogle Scholar
  13. 13.
    Bouffet E, Jakacki R, Goldman S, Hargrave D, Hawkins C, Shroff M, et al. Phase II study of weekly vinblastine in recurrent or refractory pediatric low-grade glioma. J Clin Oncol. 2012;30:1358–63.CrossRefPubMedGoogle Scholar
  14. 14.
    Wolff JE, Kortmann RD, Wolff B, Pietsch T, Peters O, Schmid HJ, Rutkowski S, Warmuth-Metz M, Kramm C. High dose methotrexate for pediatric HGG: results of the HIT-GBM-D pilot study. J Neurooncol. 2011;102:433–42. doi: 10.1007/s11060-010-0334-2. Epub 2010 Aug 8.CrossRefPubMedGoogle Scholar
  15. 15.
    von Bueren AO, von Hoff K, Pietsch T, Gerber NU, Warmuth-Metz M, Deinlein F, et al. Treatment of young children with localized medulloblastoma by chemotherapy alone: results of the prospective, multicenter trial HIT 2000 confirming the prognostic impact of histology. Neuro Oncol. 2011;13:669–79.CrossRefGoogle Scholar
  16. 16.
    Chi SN, Gardner SL, Levy AS, Knopp EA, Miller DC, Wisoff JH, et al. Feasibility and response to induction chemotherapy intensified with high-dose methotrexate for young children with newly diagnosed high-risk disseminated medulloblastoma. J Clin Oncol. 2004; 22:4881–7.CrossRefPubMedGoogle Scholar
  17. 17.
    Packer RJ, Jakacki R, Horn M, Rood B, Vezina G, MacDonald T, Fisher MJ, Cohen B. Objective response of multiply recurrent low-grade gliomas to bevacizumab and irinotecan. Pediatr Blood Cancer. 2009;52:791–5.CrossRefPubMedGoogle Scholar
  18. 18.
    Hwang EI, Jakacki RI, Fisher MJ, Kilburn LB, Horn M, Vezina G, Rood BR, Packer RJ. Long-term efficacy and toxicity of bevacizumab-based therapy in children with recurrent low-grade gliomas. Pediatr Blood Cancer. 2013;60:776–82.CrossRefPubMedGoogle Scholar
  19. 19.
    Gururangan S, Fangusaro J, Poussaint TY, Onar-Thomas A, Gilbertson RJ, Vajapeyam S, et al. Lack of efficacy of bevacizumab 1 irinotecan in cases of pediatric recurrent ependymoma—a Pediatric Brain Tumour Consortium study. Neuro Oncol. 2012;14:1404–12.CrossRefPubMedCentralPubMedGoogle Scholar
  20. 20.
    Gururangan S, Chi SN, Poussaint TY, Onar-Thomas A, Gilbertson RJ, Vajapeyam S, et al. Lack of efficacy of bevacizumab plus irinotecan in children with recurrent malignant glioma and diffuse brainstem glioma: a Pediatric Brain Tumour Consortium study. J Clin Oncol. 2010;28:3069–75.CrossRefPubMedCentralPubMedGoogle Scholar
  21. 21.
    Jahnke K, Kraemer DF, Knight KF, Fortin D, Bell S, Doolittle ND, Muldoon LL, Neuwelt EA. Intraarterial chemotherapy and osmotic blood-brain barrier disruption for patients with embryonal and germ cell tumours of the central nervous system. Cancer. 2008;112:581–8.CrossRefPubMedGoogle Scholar
  22. 22.
    Dahlborg SA, Petrillo A, et al. The potential for complete and durable response in nonglial primary brain tumours in children and young adults with enhanced chemotherapy delivery. Cancer J Sci Am. 1998;4: 110–24.PubMedGoogle Scholar
  23. 23.
    Lassaletta A, Lopez-Ibor B, Mateos E, Gonzalez-Vicent M, Perez-Martinez A, Sevilla J, Diaz MA, Madero L. Intrathecal liposomal cytarabine in children under 4 years with malignant brain tumours. J Neurooncol. 2009;95:65–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Slavc I, Schuller E, Falger J, Gunes M, Pillwein K, Czech T, Dietrich W, Rossler K, Dieckmann K, Prayer D, Hainfellner J. Feasibility of long-term intraventricular therapy with mafosfamide (n = 26) and etoposide (n = 11): experience in 26 children with disseminated malignant brain tumours. J Neurooncol. 2003;64:239–47.CrossRefPubMedGoogle Scholar
  25. 25.
    Conroy S, Garnett M, Vloeberghs M, Grundy R, Craven I, Walker D. Medulloblastoma in childhood: revisiting intrathecal therapy in infants and children. Cancer Chemother Pharmacol. 2010;65:1173–89.CrossRefPubMedGoogle Scholar
  26. 26.
    Dastoli PA, Nicacio JM, Silva NS, Capellano AM, Toledo SRC, Ierardi D, Cavalheiro S. Cystic craniopharyngioma: intratumoural chemotherapy with alpha interferon. Arq Neuropsiquiatr. 2011;69:50–5.CrossRefPubMedGoogle Scholar
  27. 27.
    Mottolese C, Stan H, Hermier M, Berlier P, Convert J, Frappaz D, Lapras C. Intracystic chemotherapy with bleomycin in the treatment of craniopharyngiomas. Childs Nerv Syst. 2001;17:724–30.CrossRefPubMedGoogle Scholar
  28. 28.
    Cho WS, Kim SK, Wang KC, Phi JH, Cho BK. Vasculopathy after intracystic bleomycin administration for a recurrent cystic craniopharyngioma. J Neurosurg Pediatr. 2012;9:394–9.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of Pediatrics, Division of Hematology/OncologyMcMaster Children’s HospitalHamiltonCanada
  2. 2.Department of Pediatrics, Division of Hematology/Oncology, Children’s Hospital of Eastern OntarioUniversity of OttawaOttawaCanada

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